A clinicopathologic and immunohistochemical study of 22 intraductal papillary mucinous neoplasms of the pancreas, with a review of the literature.

Paal E, Thompson LD, Przygodzki RM, Bratthauer GL, Heffess CS.
Mod Pathol. 1999 May;12(5):518-28.
Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are rare lesions. We undertook this study to analyze these tumors by focusing on the diagnostic criteria and correlating the histologic features with clinical prognosis. Twenty-two cases of IPMN were retrieved from the Endocrine Tumor Registry of the Armed Forces Institute of Pathology. Blocks or unstained slides were available for histochemical and immunohistochemical studies (including proliferative markers and cell cycle regulators) and K-ras oncogene mutations in 15 cases. Patient follow-up was obtained in all of the cases. IPMN occurs in both genders with a slight male predominance, with a mean age at presentation of 64.4 years (range, 48-85 yr). The patients presented with abdominal pain. The neoplasms were radiologically and grossly cystic, usually (18 cases of 22) located in the head of the pancreas. Histologically, the tumors consisted of intraductal papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was detected in 15 cases. Chronic pancreatitis was present in all of the cases. p27 immunoreactivity always exceeded the immunoreactivity of cyclin E. K-ras oncogene mutations were detected in two cases. Patients were treated with a complete surgical resection (n = 7) or a Whipple procedure (n = 13). Only 2 of 22 patients died of disease (3 died immediately postoperatively and 3 died of unrelated causes), whereas the remaining 14 patients were alive at last follow-up, without evidence of disease, an average of 58.2 months after initial presentation. IPMNs are rare, distinctive neoplasms, with complex intraductal papillae, that can be easily separated from in situ ductal adenocarcinoma and mucinous cystic neoplasms. The high ratio of p27 protein to cyclin E supports the excellent prognosis of these neoplasms, despite the presence of invasion and K-ras oncogene mutation.
PubMed ID: 10349991
Article Size: 8.5 MB

A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature.

Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS.
Ann Diagn Pathol. 2001 Jun;5(3):129-40.
Anaplastic pancreatic carcinomas are rare tumors, frequently displaying a variety of growth patterns. The literature lacks a comprehensive study of this tumor. Thirty-five cases of anaplastic carcinoma of the pancreas diagnosed between 1955 and 1997 were retrieved from the Endocrine Registry at the Armed Forces Institute of Pathology. Histology, immunophenotype, molecular analysis, and patient follow-up were analyzed. The tumors of 10 women and 25 men, aged 34 to 85 years (mean age at presentation, 62.5 years), were studied. Patients had vague symptoms (weight loss, pain, and fatigue, nausea, or vomiting), lasting an average of 13.2 weeks. The tumors, of an average size of 9.2 cm, were usually in the head or tail of the pancreas. The tumors were widely infiltrative, histomorphologically separated into predominantly large, pleomorphic cell, or spindle cell groups. Tumor phagocytosis and necrosis were noted. Immunohistochemical studies confirmed an epithelial origin with at least one epithelial marker in 78% of the tumors. K-ras mutations by sequence analysis were found in eight of 12 cases tested. Surgical biopsy/excision was used in all patients. Twenty-nine of 35 patients died of disease (average, 5.2 months), three died with no evidence of disease (average, 56.9 months), and three patients were alive at last follow-up (average, 94.0 months), one with residual disease. There was no statistically significant difference in survival between patients with and without a K-ras mutation. Anaplastic carcinoma of the pancreas usually occurs in the head of the pancreas in older men. The epithelial nature of the pleomorphic cells (giant or spindled) can usually be documented. Patients with K-ras mutations have a shorter survival time, even though the overall prognosis for all anaplastic carcinomas is fatal (93% fatality; average survival, 448 days). Ann Diagn Pathol 5: 129-140, 2001. This is a US government work. There are no restriction on its use.
PubMed ID: 11436166
Article Size: <1 MB

A clinicopathologic and immunohistochemical study of ten pancreatic lymphangiomas and a review of the literature.

Paal E, Thompson LD, Heffess CS.
Cancer. 1998 Jun 1;82(11):2150-8. — Erratum in: Cancer 1998 Aug 15;83(4):824.
BACKGROUND: Pancreatic lymphangiomas are rare benign tumors, of which only a few cases have been reported in the literature. In this study, the authors present a series of primary pancreatic lymphangiomas.
METHODS: Cases of nonepithelial pancreatic cystic tumors (lymphangiomas) diagnosed between 1966 and 1994 were retrieved from the Endocrine Pathology Registry of the Armed Forces Institute of Pathology. Histologic features (in 10 cases) as well as histochemical and immunohistochemical studies (in 6 cases) were reviewed. Long term patient follow-up data were obtained in 9 cases.
RESULTS: The patients included 8 females and 2 males ages 2-61 years (mean age, 28.9 years) at initial presentation. The tumors were circumscribed and occurred predominantly (in 6 of 10 cases) in the tail of the pancreas. The multicystic, serous, or chylous fluid-filled cystic tumors ranged from 3 to 20 cm (average, 12.7 cm) in greatest dimension. Histologically, the tumors consisted of multilocular cystic spaces of various sizes, lined by endothelial cells. The stroma contained smooth muscle and mature lymphocytes. Immunohistochemistry determined the endothelial lining cells to be factor VIII-R antigen and CD31 positive (in all cases tested) but usually CD34 negative. All patients for whom follow-up data were obtained (n=9) were alive without evidence of disease an average of 7.2 years after initial diagnosis.
CONCLUSIONS: Pancreatic lymphangiomas occur predominantly in females within a wide age range. Multilocular, fluid-filled cysts, with endothelial immunoreactivity for factor VIII-R antigen and CD31, are characteristic of these tumors. Complete surgical excision of these benign tumors resulted in excellent long term prognoses for all patients studied.
PubMed ID: 9610694
Article Size: <1 MB

A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature.

Thompson LD, Wieneke JA, Paal E, Frommelt RA, Adair CF, Heffess CS.
Cancer. 2001 Feb 1;91(3):505-24.
BACKGROUND: The criteria for minimally invasive (low grade) follicular carcinoma of the thyroid (MI) remain controversial, often resulting in unnecessary treatment.
METHODS: The records of 130 patients with minimally invasive (MI) follicular thyroid carcinoma were retrieved from the files of the Endocrine Tumor Registry of the Armed Forces Institute of Pathology.
RESULTS: Ninety-five patients were confirmed to have MI based on the authors’ criteria of small-to-medium vessel invasion, capsular invasion of up to full thickness, no parenchymal tumor extension, and no tumor necrosis (patients with oxyphilic tumors were excluded). The remaining 35 patients had tumors that were reclassified as ‘not low grade’ based on large vessel invasion, extension into parenchyma, and tumor necrosis (oxyphilic cases excluded). The MI patients included 67 women and 28 men, ages 20-95 years (average, 42.0 years). Nearly all patients presented with a thyroid mass (n = 90 patients). The mean tumor size was 2.8 cm. Histologic features examined for tumor classification included cellularity, capsule nature, capsular invasion, vascular invasion, extension into parenchyma, cytoplasmic oxyphilia, mitotic activity, and necrosis. All patients were treated with surgical excision. Adjuvant radioactive iodine therapy was performed in 24 patients. Five patients developed recurrent disease: four were alive or had died without evidence of disease after additional treatment (mean, 18.1 years), and one patient died with disease (MI tumor) at 15.1 years. All of the remaining patients were disease free (mean follow-up, 16.5 years).
CONCLUSIONS: There are reproducible histologic criteria to diagnose patients with MI follicular carcinoma. The overall excellent long term prognosis and a good patient outcome suggests that no additional surgery is necessary. Copyright 2001 American Cancer Society.
PubMed ID: 11169933
Article Size: 2 MB

A rationale for conservative management of microscopic papillary carcinoma of the thyroid gland: a clinicopathologic correlation of 90 cases.

Rassael H, Thompson LD, Heffess CS.
Eur Arch Otorhinolaryngol. 1998;255(9):462-7.
Microscopic papillary carcinoma of the thyroid gland (MPC) measuring < or = 1.0 cm in diameter has a generally benign outcome, but is often overtreated with additional surgery. Ninety cases of MPC and 77 cases of nonmicroscopic papillary carcinoma of the thyroid gland (non-MPC) from 1970 to 1980 were retrieved from the Endocrine Registry of the Armed Forces Institute of Pathology (AFIP), Washington, D.C. Histologic features and patient follow-up were analyzed. Twenty-one patients with MPC had multifocal disease within the affected thyroid lobe, while a further 15 had either bilateral or intraglandular spread. Four of 10 patients who had additional surgery were found to have additional foci of tumor. Fourteen patients with lymph node metastases at initial surgery had no subsequent nodal metastases. All patients were either alive without disease or had died of unrelated causes after an average follow-up period of 17.3 years. Of the 77 non-MPC patients, 13 developed lymph node metastases or local recurrences, and one died of metastatic disease. Sixty-four of these patients were alive without evidence of disease after an average follow-up of 22 years. Present findings show that while MPC may present with perithyroidal lymph node metastases (15.56%), patients do not develop clinical tumors in the remaining thyroid tissue. Our experience indicates that close clinical follow-up without additional surgery is the preferable management for patients with MPC.
PubMed ID: 9833215
Article Size: <1 MB

Adenosquamous carcinoma of the pancreas: a clinicopathologic series of 25 cases.

Kardon DE, Thompson LD, Przygodzki RM, Heffess CS.
Mod Pathol. 2001 May;14(5):443-51.
BACKGROUND: Adenosquamous carcinoma is a rare aggressive subtype of pancreatic adenocarcinoma. We describe the clinical, pathologic, and molecular characteristics of 25 of these lesions, the largest series to date.
METHODS: Twenty-five cases of adenosquamous carcinoma of the pancreas diagnosed between 1961 and 1994 were retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology. Histologic features were reviewed, histochemical, immunohistochemical, and molecular (k-ras) studies were performed, and patient follow-up was obtained.
RESULTS: The patients included 17 men and eight women, aged 28 to 82 years (mean, 65.4 y). The patients usually experienced weight loss (n = 17) or painless jaundice (n = 11), while also presenting with other abdominal symptoms. The tumors affected the head most frequently (n = 17), followed by the tail (n = 9) or body (n = 4). Five cases involved more than one anatomic region of the pancreas. Microscopically, all tumors demonstrated dual differentiation toward adenocarcinoma and squamous cell carcinoma. All cases tested were immunoreactive with keratin (AE1:AE3 and CK1), whereas other keratin markers were variably expressed: CK5/6 (88%), CK7 (68%), Cam5.2 (41%), and CK20(26%). CA-19-9 (84%) and CEA (74%) were positive in the majority of the cases. K-ras oncogene mutations were identified in seven of 13 cases. All patients died from their disease an average of 5.8 months after diagnosis (range, 1 to 33 months).
CONCLUSIONS: Adenosquamous carcinoma of the pancreas represents a distinct clinical and pathologic entity, demonstrating the expected immunoprofile and k-ras oncogene mutation of a ductal origin, with a worse prognosis than ductal adenocarcinoma.
PubMed ID: 11353055
Article Size: 2.5 MB

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients.

Wieneke JA, Thompson LD, Heffess CS.
Am J Surg Pathol. 2003 Jul;27(7):867-81.
Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.
PubMed ID: 12826878
Article Size: 2 MB

Chronic lymphocytic thyroiditis (Hashimoto thyroiditis).

Thompson LD.
Ear Nose Throat J. 2014 Apr-May;93(4-5):152-3.
FIRST PARAGRAPH: Chronic lymphocytic thyroiditis, eponymically referred to as Hashimoto thyroiditis (named after Hakarum Hashimoto, who first described the disease in 1912), is an autoimmune thyroiditis that results from autoantibodies to thyroid-specific antigens. There is a poorly understood interaction between susceptibility genes and environmental triggers, resulting in antimicrosomal and antithyroglobulin antibodies. Many patients may have another simultaneous autoimmune disease (such as Sjögren syndrome, diabetes mellitus, or myasthenia gravis), while there is some overlap with Graves disease (diffuse hyperplasia). Hypothyroidism may also result from destruction of the thyroid epithelium by inflammatory cells.
PubMed ID: 24817227
Article Size: <1 MB

Corticomedullary mixed tumor of the adrenal gland.

Wieneke JA, Thompson LD, Heffess CS.
Ann Diagn Pathol. 2001 Oct;5(5):304-8.
Corticomedullary mixed tumors of the adrenal gland are quite rare, with only five well-documented cases reported in the literature.(1-4) Herein, we report the light microscopic and immunohistochemical features of two cases of this rare tumor. Patient 1 is a 34-year-old woman who presented with hypertension, hair loss, and amenorrhea of 1-year duration. Patient 2 is a 52-year-old woman who presented with flank pain and what appeared to be a renal mass on arteriogram with no history of hypertension, Cushing’s syndrome, or other endocrine abnormalities. At surgery, the tumor was noted to arise from the adrenal gland rather than the kidney and adrenalectomy was performed. In both cases, the surgically resected specimens consisted of a well-circumscribed, single adrenal mass surrounded by a rim of uninvolved adrenal cortical tissue. The tumors were composed of adrenal cortical cells intimately admixed with pheochromocytes. Immunohistochemical studies highlighted these two cellular components. The pheochromocytes were strongly reactive with chromogranin and the sustentacular cells with S-100 protein, whereas the adrenal cortical cells reacted specifically with inhibin. Thus, we report two additional cases of mixed corticomedullary tumor of the adrenal gland. Ann Diagn Pathol 5:304-308, 2001. This is a US government work. There are no restrictions on its use.
PubMed ID: 11598859
Article Size: <1 MB

Diffuse sclerosing variant of papillary thyroid carcinoma: a clinicopathologic and immunophenotypic analysis of 22 cases.

Thompson LD, Wieneke JA, Heffess CS.
Endocr Pathol. 2005 Winter;16(4):331-48.
BACKGROUND: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon tumor making up about 2% of all papillary thyroid carcinomas. Previous studies have not comprehensively evaluated these tumors in a large series of patients.
DESIGN: Twenty-two cases of DSV-PTC diagnosed between 1970 and 2000 were identified in the files of the AFIP. Histologic and immunohistochemical features were evaluated and patient follow-up was obtained.
RESULTS: The tumors affected 14 females and 8 males, aged 6 to 49 yr (mean, 18 yr), with males presenting at a mean older age than females (24 vs 14 yr). Symptoms included an enlarging mass in the thyroid, present for a mean of 9.5 mo. While a dominant tumor was identified in a single lobe, bilateral disease was common (n = 16). The dominant mass ranged in size from 1.7 to 5.8 cm in diameter (mean, 3.8 cm). Histologically, all cases demonstrated a papillary carcinoma (conventional, solid, or follicular pattern) diffusely involving the gland. Extrathyroidal extension, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis/sclerosis, and psammoma bodies were present to a variable degree. Both the papillary carcinoma and squamous metaplasia cells were strongly immunoreactive with CK19, thyroglobulin, and TTF-1. An increased number of S-100 protein immunoreactive dendritic cells were recognized. p53 was increased (>15%) in the tumor cells in 12 patients, while Ki-67 was increased in the tumor cells in two patients. Perithyroidal and cervical lymph node metastasis occurred in 18 (82%) patients. All metastases demonstrated histologic features similar to the primary. Complete resection (thyroidectomy in 18 patients) with lymph node dissection, yielded a 95% 5-yr survival without evidence of disease. One patient died of disease after a malignant transformation of the squamous metaplasia into squamous cell carcinoma.
CONCLUSIONS: The recognition of DSV-PTC can be made with the following features: classic to solid foci of PTC, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis, and innumerable psammoma bodies. DSV-PTC is more biologically aggressive than conventional PTC, but the patients’ survival is not significantly different. This diagnosis should lead the clinician to aggressively manage these patients (thyroidectomy and lymph node dissection) in an effort to achieve an excellent long-term clinical outcome.
PubMed ID: 16627920
Article Size: <1 MB

Dyshormonogenetic goiter of the thyroid gland.

Thompson LD.
Ear Nose Throat J. 2005 Apr;84(4):200.
FIRST PARAGRAPH: Dyshormonogenetic goiter is the name given to a family of inborn errors of metabolism that lead to defects in the synthesis of thyroid hormone. The prevalence of this disease is 1 in 30,000 to 50,000 live births, and it is the second most common cause (10 to 15%) of permanent congenital hypothyroidism.
PubMed ID: 15929313
Article Size: <1 MB

Endoscopic management of intratracheal ectopic thyroid.

Pritchyk KM, Thompson LD, Malekzadeh S.
Otolaryngol Head Neck Surg. 2004 May;130(5):630-2.
CASE REPORT CONCLUSIONS: ITET is a rare cause of upper airway obstruction. CT scan of the neck without contrast should be performed to evaluate the location of obstruction. MRI scan should be used to assess the extent and vascular nature of the lesion. Endoscopic laser excision is an appropriate treatment option for benign and vascular ITET tissue.
PubMed ID: 15138431
Article Size: <1 MB

Hyalinizing trabecular adenoma of the thyroid gland.

Thompson LD.
Ear Nose Throat J. 2011 Sep;90(9):416-7.
FIRST PARAGRAPH: Hyalinizing trabecular ade-noma (HTA) is a very rare tumor (<1% of all primary thyroid gland tumors) of thyroid follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. For all intents and purposes, this is a benign tumor, although there is a case report of pulmonary metastasis with invasion, suggesting the term tumor be used instead of adenoma. A few cases have occurred following radiation exposure, and there may be a relationship to thyroid papillary carcinoma, as there have been reports of RET/PTC rearrangements.
PubMed ID: 21938699
Article Size: <1 MB

Intratracheal ectopic thyroid tissue: a case report and literature review.

Byrd MC, Thompson LD, Wieneke JA.
Ear Nose Throat J. 2003 Jul;82(7):514-8.
We discuss a case of intratracheal ectopic thyroid tissue (ETT) that was retrieved from the files of the Otorhinolaryngic–Head and Neck Pathology Registry at the Armed Forces Institute of Pathology. The patient was a 54-year-old man who had a history of papillary thyroid carcinoma, which had been treated with a subtotal thyroidectomy. During routine follow-up 4 years later, the patient’s primary care physician detected an elevated thyroglobulin level. Further referrals and evaluations revealed that the patient had intratracheal ETT. The patient refused to undergo surgical excision and remains without evidence of recurrent carcinoma. In a MEDLINE literature review, we found only 13 other well-documented cases of intratracheal ETT since 1966; in all but two cases, patients had benign disease. Once the possibility of thyroid carcinoma has been eliminated by histologic examination, intratracheal ETT can be managed by complete surgical excision with the prospect of an excellent long-term clinical outcome.
PubMed ID: 12955837
Article Size: <1 MB

Langerhans cell histiocytosis of the thyroid: a series of seven cases and a review of the literature.

Thompson LD, Wenig BM, Adair CF, Smith BC, Heffess CS.
Mod Pathol. 1996 Feb;9(2):145-9.
Langerhans cell histiocytosis is a rare disorder, with a few reports describing isolated thyroid gland involvement. We report seven cases, which included four females and three males ranging in age from 2 months to 55 years, with a median age of 37 years. Histologically, the cases demonstrated either diffuse or focal involvement of the thyroid gland by Langerhans cell histiocytes, characterized by bean-shaped, lobated, folded nuclei. In association with the histiocytic infiltrate, there was a prominent eosinophilic cellular component, as well as destruction of the thyroid follicles. All cases occurred in a background of lymphocytic thyroiditis. One case demonstrated adenomatoid nodules, whereas another had a microscopic papillary carcinoma. Immunohistochemical staining demonstrated positive reactivity with S-100 protein, lysozyme, and KP-1. Four patients with isolated thyroid disease, treated by surgical resection alone, are alive without systemic disease from 3 to 19 years after initial presentation. The three patients with systemic disease died within 1 year of the initial diagnosis with disease-related complications. Localized disease portends a favorable prognosis as compared to the thyroid involvement as part of systemic disease.
PubMed ID: 8657721
Article Size: 3 MB

Malignant lymphoma of the thyroid gland: a clinicopathologic study of 108 cases.

Derringer GA, Thompson LD, Frommelt RA, Bijwaard KE, Heffess CS, Abbondanzo SL.
Am J Surg Pathol. 2000 May;24(5):623-39.
We report a retrospective clinicopathologic study of 108 primary thyroid gland lymphomas (PTLs), classified using the REAL and proposed WHO classification schemes. The patients included 79 women and 29 men, with an average age of 64.3 years. All patients presented with a thyroid mass. The PTLs were classified as marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) or MZBL (n = 30), diffuse large B-cell lymphoma (DLBCL) with MZBL (n = 36), DLBCL without MZBL (n = 41), and follicle center lymphoma (FCL; n = 1). Excluding the FCL, features of lymphomas of MALT-type were identified in all groups, despite a follicular architecture in 23% of cases. Lymphocytic thyroiditis (LT) was identified in 94%. Ninety-one percent of patients presented with stage IE or IIE disease, whereas 69% had perithyroidal soft tissue infiltration. All patients were treated with surgical excision followed by adjuvant therapy (76%): chemotherapy (15%), radiation (19%), or a combination of radiation and chemotherapy (42%). Disease-specific survival was 82% at last follow up (mean, 82.8 mos) and 79% at 5 years. Statistically, stages greater than IE, presence of DLBCL, rapid clinical growth, abundant apoptosis, presence of vascular invasion, high mitotic rate, and infiltration of the perithyroidal soft tissue were significantly associated with death with disease. No patients with MZBL or stage IE disease died with disease. In summary, PTLs typically occur in middle- to older-aged individuals as a thyroid mass, with a predilection for females. Despite their histologic heterogeneity and frequent simulation of other lymphoma subtypes, virtually all PTLs are lymphomas of MALT-type arising in the setting of LT. Mixed DLBCL and MZBL are common. Overall, PTLs have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and histology. MZBL and stage IE tumors have an excellent prognosis, whereas tumors with a large cell component or DLBCL or stage greater than IE have the greatest potential for a poor outcome.
PubMed ID: 10800981
Article Size: 4 MB

Medullary thyroid carcinoma.

Thompson LD.
Ear Nose Throat J. 2010 Jul;89(7):301-2.
FIRST PARAGRAPH: Medullary thyroid carcinoma (MTC) is a malignant epithelial tumor of the thyroid gland that exhibits C-cell differentiation. C cells arise from the ultimobranchial body, which is derived from the fourth pharyngeal pouch, and they are found in the upper and middle areas of the thyroid lobes. These cells produce calcitonin, a hormone involved in calcium homeostasis. While a number (20%) of MTCs are associated with the autosomal-dominant inherited multiple endocrine neoplasia (MEN) syndromes (specifically MEN2A and MEN2B), most (80%) cases are sporadic. Germline or somatic mutations of the RET gene are characteristic of this tumor. They usually involve an activating point mutation of 10q11.2. Specifically, codon 634 in exon 11 is most common in MEN2A, while codon 918 in exon 16 is most common in MEN2B.
PubMed ID: 20628986
Article Size: <1 MB

Metastatic renal cell carcinoma to the thyroid gland: a clinicopathologic study of 36 cases.

Heffess CS, Wenig BM, Thompson LD.
Cancer. 2002 Nov 1;95(9):1869-78.
BACKGROUND: Clear cell tumors of the thyroid gland in general are uncommon. Metastatic renal cell carcinoma (RCC) to the thyroid gland is a rare occurrence but must be considered in the differential diagnosis of a thyroid gland clear cell neoplasm to prevent misclassification, potentially resulting in inappropriate clinical management.
METHODS: Thirty-six cases of metastatic RCC to the thyroid were retrospectively retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology.
RESULTS: The tumors occurred in 22 women and 14 men, ages 53-80 years (mean, 64.9 years). Symptoms were present for a mean of 13.0 months. The tumors generally affected a single lobe of the thyroid gland as a solitary mass (n = 30; 83%), measuring 1.0-15.0 cm in diameter (mean, 3.8 cm). Histologically, the tumors were composed of polygonal cells with clear cytoplasm, distinct cell membranes, and small compact eccentric nuclei within a rich vascular network. Diastase-sensitive, periodic acid-Schiff-positive material (n = 22; 61%) and/or Oil Red O-positive material (n = 5; 14%) were noted. Thyroglobulin immunohistochemistry was negative in the foci of metastatic RCC. Although the majority of the patients had documented previous evidence of an RCC (n = 23; 64%) as remotely as 21.8 years before the thyroid metastases (mean, 9.4 years), the metastatic tumor to the thyroid gland was the initial manifestation of RCC in 13 patients. The majority of patients (n = 23; 64%) died with disseminated disease (mean, 4.9 years), but 13 patients (36%) were alive or had died without evidence of disease (mean, 9.1 years).
CONCLUSIONS: In the presence of a clear cell tumor of the thyroid gland, the diagnostic considerations must include metastatic RCC. The light microscopic features may suggest this possibility and the diagnosis can be established by supplemental histochemical and immunohistochemical studies. Surgical treatment of the metastatic disease is suggested, as this may result in prolonged patient survival. Published 2002 by the American Cancer Society.
PubMed ID: 12404280
Article Size: 2 MB

Minimally invasive follicular thyroid carcinoma.

Heffess CS, Thompson LD.
Endocr Pathol. 2001 Winter;12(4):417-22.
Infiltration of the capsule, vascular invasion, and/or neoplastic extension into the adjacent parenchyma are regarded as prerequisites for the diagnosis of follicular carcinoma. In modern practice, most of these tumors fall into the category of follicular carcinoma, minimally invasive (FCMI) characterized by evidence of limited capsular or vascular invasion with an excellent long-term prognosis and a good patient outcome. Notwithstanding the wide acceptance of the diagnostic criteria established by the World Health Organization for the classification of follicular carcinomas in particular, they have been difficult to apply and have led to a great deal of confusion. This confusion is compounded when applied to ‘low-grade’ or ‘minimally invasive’ follicular carcinoma because of the poor reproducibility of the classification and the variable results reported in the literature. Our surgical colleagues face a similar lack of a standardized treatment for low-grade follicular carcinomas, which leads to unnecessary surgical treatment. Standardization of histologic criteria is necessary to promote confidence and uniformity in the therapeutic approach of these tumors. We believe that a FCMI is defined as an encapsulated follicular tumor (not papillary), with only small to medium vessel invasion within or immediately adjacent to the tumor capsule and/or up to full-thickness capsular transgression without accompanying extension into the thyroid parenchyma with intervening fibrosis. By using these criteria, patients can be managed with conservative surgical excision to yield an excellent long-term patient outcome.
PubMed ID: 11914475
Article Size: 1 MB

Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis.

Thompson L, Chang B, Barsky SH.
Am J Surg Pathol. 1996 Mar;20(3):277-85.
Malignant mixed tumors (carcinosarcomas) are examples of unusual neoplasms whose occurrences have been observed in increasingly diverse sites but whose pathogenesis remains a complete mystery. Two antithetical hypotheses that have been advanced to explain the histogenesis of these tumors include the convergence hypothesis, which proposes an origin from two or more stem cells (multiclonal hypothesis), and the divergence hypothesis, which proposes an origin from a single totipotential stem cell that differentiates into separate epithelial and mesenchymal directions (monoclonal hypothesis). To test these hypotheses, a novel strategy for the determination of clonality from as few as 100 tumor cells obtained by enzymatic digestion of either fresh or formalin-fixed, paraffin-embedded tissues and cell sorting was used that exhibited the polymerase chain reaction (PCR) in amplifying a 511-bp region located within the first intron of the human hypoxanthine phosphoribosyl transferase gene, a site that contains inactive X chromosomal obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5% females. Carcinoma cells gated on the basis of fluorescein isothiocyanate (FITC)-anti-cytokeratin and sarcoma cells gated on the basis of FITC-antivimentin or FITC-anti-desmin were sorted to homogeneity on FACSTAR and then subjected to genomic DNA extraction and Hpa II digestion before PCR amplification and subsequent analysis of the product on denaturing gradient gel electrophoresis. The comigrations of the single homoduplexes generated from both the carcinoma cells and sarcoma cells in six different malignant mixed tumors obtained from four different organs indicated clonal identity and monoclonality in all cases. These findings of monoclonality were confirmed independently by two other methods of clonality determination. The findings of a monoclonal origin of carcinosarcomas support the single totipotential stem-cell-divergence hypothesis.
PubMed ID: 8772780
Article Size: 2.5 MB

Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: a clinicopathologic study of 130 cases.

Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS.
Am J Surg Pathol. 1999 Jan;23(1):1-16.
Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon tumors. The classification and biologic potential of these neoplasms remain the subject of controversy. Attempts to classify these tumors in a similar manner to ovarian MCNs remains controversial, as even histologically benign-appearing pancreatic MCNs metastasize and are lethal. One hundred thirty cases of MCNs were identified in the files of the Endocrine Pathology Tumor Registry of the Armed Forces Institute of Pathology from the years 1979 to 1993. The pathologic features, including hematoxylin and eosin staining, histochemistry, immunohistochemistry (IHC), cell cycle analysis, and K-ras oncogene determination were reviewed. These findings were correlated with the clinical follow-up obtained in all cases. There were 130 women, aged 20-95 years (mean age at the outset, 44.6 years). The patients had vague abdominal pain, fullness, or abdominal masses. More than 95% of the tumors were in the pancreatic tail or body and were predominantly multilocular. The tumors ranged in size from 1.5 to 36 cm in greatest dimension, with the average tumor measuring >10 cm. A spectrum of histomorphologic changes were present within the same case and from case to case. A single layer of bland-appearing, sialomucin-producing columnar epithelium lining the cyst wall would abruptly change to a complex papillary architecture, with and without cytologic atypia, and with and without stromal invasion. Ovarian-type stroma was a characteristic and requisite feature. Focal sclerotic hyalinization of the stroma was noted. This ovarian-type stroma reacted with vimentin, smooth muscle actin, progesterone, or estrogen receptors by IHC analysis. There was no specific or unique epithelial IHC. K-ras mutations by sequence analysis were wild type in all 52 cases tested. Ninety percent of patients were alive or had died without evidence of disease (average follow-up 9.5 years), irrespective of histologic appearance; 3.8% were alive with recurrent disease (average 10 years after diagnosis); and 6.2% died of disseminated disease (average 2.5 years from diagnosis). Irrespective of the histologic appearance of the epithelial component, with or without stromal invasion, pancreatic MCNs should all be considered as mucinous cystadenocarcinomas of low-grade malignant potential. Pancreatic MCNs cannot be reliably or reproducibly separated into benign, borderline, or malignant categories.
PubMed ID: 9888699
Article Size: 4 MB

Mucinous cystic neoplasms of the pancreas: radiologic-pathologic correlation.

Buetow PC, Rao P, Thompson LD.
Radiographics. 1998 Mar-Apr;18(2):433-49.
Mucinous cystic neoplasms of the pancreas are rare primary tumors. They have pathologic and clinical similarities to biliary cystadenomas of the liver and mucinous cystic tumors of the ovary. Mucinous cystic neoplasms of the pancreas typically affect middle-aged women and arise in the tail of the pancreas. Gross pathologic and imaging features usually are those of a large, multilocular cystic mass. There is, however, a spectrum of radiologic findings that overlaps with those of other entities including pancreatic pseudocyst, other primary epithelial and nonepithelial tumors of the pancreas, and metastases. In most cases, ultrasound and computed tomography are the mainstays for radiologic evaluation, with magnetic resonance imaging having a complementary role. All mucinous cystic neoplasms should be considered as mucinous cystadenocarcinomas of low-grade malignant potential. Complete surgical excision alone results in an excellent clinical outcome and disease-free survival, irrespective of histologic or radiologic parameters in over 90% of cases studied.
PubMed ID: 9536488
Article Size: 1.5 MB

Neoplasms metastatic to the thyroid gland.

Thompson L.
Ear Nose Throat J. 2006 Aug;85(8):480, 483.
FIRST PARAGRAPH: Tumors that occur in the thyroid gland as a result of lymph or vascular spread from distant sites are considered to represent metastatic disease rather than a direct extension of a primary from an adjacent organ. Metastatic deposits are identified at a higher frequency in abnormal glands—that is, those with adenomatoid nodules, thyroiditis, and follicular neoplasms. Further, metastatic deposits may be found within primary thyroid tumors, such as a renal cell carcinoma metastatic to a thyroid papillary carcinoma. Although a thyroid gland mass may be the presenting clinical sign, it is more often the underlying thyroid gland disease (e.g., thyroiditis, adenomatoid nodules) that prompts clinical evaluation. The thyroid gland metastatic deposit is the initial presentation of an occult primary tumor in as many as 40% of patients. Carcinomas are the most common metastatic tumors from (in order of frequency) the kidney (figure 1), lung, breast (figure 2), and stomach; melanoma is less common.
PubMed ID: 16999049
Article Size: <1 MB

Papillary thyroid carcinoma.

Nelson BL, Thompson LD.
Ear Nose Throat J. 2004 Oct;83(10):675-6.
FIRST PARAGRAPH: Papillary thyroid carcinoma is the most common type of thyroid malignancy. The tumor occurs largely in adults, usually those between the ages of 20 and 50 years; the female-to-male ratio is 4:1. Papillary thyroid carcinoma is also the most common pediatric thyroid malignancy.
PubMed ID: 15586863
Article Size: <1 MB

Parathyroid adenoma.

Thompson LD.
Ear Nose Throat J. 2014 Jul;93(7):246-68.
FIRST PARAGRAPH: A parathyroid adenoma is a benign neoplasm of parathyroid parenchymal cells. There is an association with the HRPT2 gene (1q25-q31), which is associated with hyperparathyroidism-jaw tumor syndrome (an autosomal dominant disorder). Parathyroid adenoma is the single most common cause of hyperparathyroidism. It is usually seen in patients in the fourth and fifth decades of life, and women are affected more often than men by a margin of 3 or 4 to 1.
PubMed ID: 25025408
Article Size: <1 MB

Parathyroid carcinoma occurring in multiple endocrine neoplasia type 1.

Kodroff KS, Lieber C, Thompson LDR.
Endocr Pract. 1999 Nov-Dec;5(6):347-349.
OBJECTIVE: To describe a patient with multiple endocrine neoplasia type I (MEN-I) in whom parathyroid carcinoma developed.
METHODS: A case report is presented, including detailed history, laboratory findings, and pathologic features.
RESULTS: A 49-year-old man with a known history of MEN-I syndrome had hypercalcemia and profoundly increased parathyroid hormone levels. Seven years earlier, he had been diagnosed with a gastrinoma, prolactinoma, and primary hyperparathyroidism. A neck exploration at that time consisted of resection of a right inferior parathyroid gland and parathyroid tissue in the thyroid gland as well as biopsies of two left-sided glands, after which microscopic examination revealed parathyroid hyperplasia and his serum calcium levels normalized. On reexploration of the neck, resection revealed pathologic findings consistent with parathyroid carcinoma.
CONCLUSION: Parathyroid carcinoma has rarely been reported in the setting of MEN-I. This case illustrates the need for near-complete resection of parathyroid tissue in the patient with MEN-I. Subtotal or total parathyroidectomy in conjunction with forearm autotransplantation should be performed, not simply to prevent recurrence of benign disease but also to prevent the potential development of carcinoma over time.
PubMed ID: n/a
Article Size: 1.5 MB

Parathyroid carcinoma.

Thompson LD.
Ear Nose Throat J. 2008 Sep; 87(9):502-504.
FIRST PARAGRAPH: Parathyroid carcinoma is rare, comprising less than 1% of all cases of primary hyperparathyroidism. Parathyroid carcinoma occurs in patients of all ages, and there is no predilection for either sex. Its clinical features are primarily attributable to the effects of hypercalcemia and excessive secretion of parathyroid hormone (PTH). Most of its symptoms–weakness, fatigue, anorexia, weight loss, and nausea–are nonspecific, but an excessively high serum calcium level (>16 mg/dl) can be associated with nephrolithiasis, renal insufficiency, and bone ‘brown tumors.’ A palpable neck mass suggests a parathyroid carcinoma. Parathyroid carcinoma is a suggested component of hyperparathyroidism-jaw tumor syndrome.
PubMed ID: 18800320
Article Size: <1 MB

Parathyroiditis.

Thompson LD.
Ear Nose Throat J. 2005 Oct;84(10):636.
FIRST PARAGRAPH: Parathyroiditis is a rare and poorly understood condition. Chronic parathyroiditis may occur in patients with hypoparathyroidism, as well as in those with primary chief-cell hyperplasia. Most patients are asymptomatic. Antibodies to parathyroid tissue are seen in only a few cases of parathyroiditis. It is thought that parathyroiditis represents an autoimmune process similar to thyroid gland Hashimoto’s disease. The presence of seronegative cases of parathyroiditis does not rule against an autoimmune etiology, because a similar phenomenon is observed in Hashimoto’s thyroiditis. Based on this assumption, it is believed that the lymphocytic infiltration is an ongoing destructive process.
PubMed ID: 16382744
Article Size: <1 MB

Peripheral Nerve Sheath Tumors of the Thyroid Gland: A Series of Four Cases and a Review of the Literature.

Thompson LD, Wenig BM, Adair CF, Heffess CS.
Endocr Pathol. 1996 Winter;7(4):309-318.
Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are exceptionally rare. Two schwannomas and two malignant PNSTs (MPNSTs), arising primarily within the thyroid gland, were identified in the files of the Endocrine Tumor Registry at the Armed Forces Institute of Pathology. The patients included two females, age 69 and 80 yr, and two males, age 18 and 33 yr. The patients presented with a mass in the thyroid gland confined to a single lobe of the thyroid without involvement of the cervical neck region. None of the patients had a history of neurofibromatosis. The benign tumors were encapsulated, one of them cystic, with the characteristic cellular and nuclear features of schwannomas. The MPNSTs were invasive tumors, effacing the thyroid parenchyma, with a fascicular pattern of growth composed of neural appearing cells with increased cellularity, increased mitotic activity, and with focal necrosis. Immunoreactivity for 5100 protein and vimentin was seen in all tumors. The patients with schwannomas, treated only by surgical resection, were alive without evidence of disease, over a period of 5-33 yr. Both patients with MPNSTs died of the disease 8 mo and 42 mo, respectively, with widely disseminated disease. Primary thyroid PNSTs are exceptionally rare tumors. MPNSTs, in this limited experience, have a fatal outcome irrespective of aggressive adjuvant therapy.
PubMed ID: 12114802
Article Size: 5 MB

Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases.

Thompson LD.
Am J Surg Pathol. 2002 May;26(5):551-66.
No comprehensive series has evaluated the histologic features of pheochromocytoma to separate benign from malignant pheochromocytoma by histomorphologic parameters only. Fifty histologically malignant and 50 histologically benign pheochromocytomas of the adrenal gland were retrieved from the files of the Armed Forces Institute of Pathology. The patients included 43 females and 57 males, with an age range of 3-81 years (mean 46.7 years). Patients usually experienced hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222 g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland more frequently demonstrated invasion (vascular [score = 1], capsular [score = 1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2), tumor cell spindling (score = 2), cellular monotony (score = 2), increased mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score (PASS) weighted for these specific histologic features can be used to separate tumors with a potential for a biologically aggressive behavior (PASS > or =4) from tumors that behave in a benign fashion (PASS <4). The pathologic features that are incorporated into the PASS correctly identified tumors with a more aggressive biologic behavior. Application of these criteria to a large cohort of cases will help to elucidate the accuracy of this grading system in clinical practice.
PubMed ID: 11979086
Article Size: 3 MB

Pheochromocytoma.

Thompson LDR.
Pathol Case Rev 2005;10 (5): 243-25.
Pheochromocytomas are tumors arising from the chromaffin cells of the adrenal medulla. They are equivalent to paragangliomas in other anatomic sites. They are uncommon neoplasms and most are sporadic, although 10% are described in syndromes, another 10% are bilateral (usually syndrome associated), and about 10% are malignant. They develop in both genders and peak in the fourth to fifth decades, although familial tumors occur at a younger age. Patients present clinically with the pharmacologic effects of excess catecholamines, manifested by episodic, postural, paroxysmal and/or labile hypertension, headaches, diaphoresis, palpitations, chest pain, and anxiety. Radiographic studies with nucleotide scans are often diagnostic. Malignant pheochromocytomas have historically required the presence of metastatic tumor to confirm the diagnosis of a malignant neoplasm. However, a series of histologic features, when used in conjunction with laboratory findings, radiographic findings, macroscopic features, and immunohistochemical results, can help to prospectively diagnose malignant heochromocytoma. These features include invasion, large nests or diffuse growth (loss of Zellballen architecture), focal or confluent necrosis, high cellularity, tumor cell spindling, cellular monotony, increased mitotic figures, atypical mitotic figures, profound nuclear pleomorphism, and hyperchromasia. Overall, the patient prognosis for benign pheochromocytoma is excellent, although that for malignant pheochromocytoma is intermediate, with surgery achieving the best clinical result of about 75% 5-year survival. Separation from benign pheochromocytoma and adrenal cortical neoplasms is important as the management is different.
PubMed ID: n/a
Article Size: 4 MB

Pituitary adenoma.

Thompson LD.
Ear Nose Throat J. 2006 Mar;85(3):152-3.
FIRST PARAGRAPH: Pituitary tumors account for approximately 15% of all intracranial neoplasms. They can be either benign or malignant, primary or secondary, and epithelial or nonepithelial. Pituitary carcinoma can only be diagnosed when there is confirmed metastatic disease. The vast majority are primary epithelial pituitary adenomas, which generally arise from hormone-producing cells, regardless of whether a particular tumor is active or inactive (i.e., non-hormone-producing). Pituitary adenomas are further classified on the basis of size, function, cell type, hormone production, location, and biologic behavior. Most pituitary adenomas are benign neoplasms, either null-cell or prolactin-producing microadenomas (<1 cm in their greatest dimension -- usually seen radiographically) that are seen within the pituitary gland. Most pituitary adenomas occur in women; they can arise at any age, but they are more common in the third through sixth decades of life. Patients with a pituitary adenoma present with either an endocrinopathy or a mass effect. Nonfunctioning adenomas exhibit no biochemical or clinical evidence of excessive hormone production. Patients with functional tumors present with specific syndromes, such as Cushing’s syndrome (adrenocorticotropic hormone-producing).
PubMed ID: 16615592
Article Size: <1 MB

Primary Paraganglioma of the Parathyroid: A Case Report and Clinicopathologic Review.

Levy MT, Braun JT, Pennant M, Thompson LDR.
Head Neck Pathol. 2010 Mar;4(1):37-43.
Paragangliomas are relatively uncommon neoplasms that arise in adrenal and extra-adrenal paraganglia of the autonomic nervous system. Parasympathetic paraganglioma develop predominantly in the head and neck. It is exceedingly uncommon to develop a primary intraparathyroid paraganglioma. There is only a single case report in the English literature. The information from the single previous case report (Medline 1960–2009) was combined with this case report. Our patient was a 69 year old woman who presented with a thyroid gland mass, with extension into the substernal space. The patient had a history of renal cell carcinoma removed 18 months before. At surgery, a thyroid lobectomy and a parathyroidectomy were performed. The parathyroid tissue showed a very well defined zellballen arrangement of paraganglion cells within the parenchyma of the parathyroid gland. The cells had ample basophilic, granular cytoplasm. The nuclei were generally round to oval with ‘salt-and-pepper’ nuclear chromatin distribution. There was a richly vascularized stroma. Mitotic figures, necrosis, invasive growth, and profound nuclear pleomorphism were absent. The neoplastic cells were strongly and diffusely immunoreactive with chromogranin, synaptophysin, CD56, and focally with cyclin-D1. The paraganglioma showed a delicate S-100 protein positive supporting sustentacular framework. Keratin, CD10, PTH, calcitonin and RCC markers were negative. The patient showed no stigmata of Multiple Endocrine Neoplasia (MEN) and has no paraganglioma in any other anatomic site. She is alive without any additional findings 12 months after surgery. Isolated paraganglioma within the parathyroid is rare, and should be separated from parathyroid adenoma, hyperplasia or metastatic disease to assure appropriate management.
PubMed ID: 20237987
Article Size: <1 MB

Primary parathyroid hyperplasia.

Penner CR, Thompson LD.
Ear Nose Throat J. 2003 May;82(5):363.
FIRST PARAGRAPH: Parathyroid hyperplasia is classified as either primary, secondary, or tertiary. Primary parathyroid hyperplasia occurs in approximately 15% of patients with hyperparathyroidism. Most cases are sporadic, and they usually occur in patients who are middle-aged and older. Approximately 20% of all cases of primary chief-cell hyperplasia are associated with one of the multiple endocrine neoplasia syndromes. Symptoms are referable to the level and duration of serum calcium elevation, although routine biochemical testing has led to an increase in the identification of asymptomatic patients. Biochemically, ionized serum calcium levels are elevated, and serum phosphorus concentrations are lowered. Technetium-99m sestamibi imaging successfully localizes as many as 60% of hyperplastic glands, although this technique is significantly more effective in localizing adenomas and carcinomas. Therefore, at least two glands should be examined histologically to confirm the diagnosis.
PubMed ID: 12789760
Article Size: <1 MB

Primary smooth muscle tumors of the thyroid gland.

Thompson LD, Wenig BM, Adair CF, Shmookler BM, Heffess CS.
Cancer. 1997 Feb 1;79(3):579-87.
BACKGROUND: Primary smooth muscle tumors of the thyroid gland are rare. To date, there are few cases reported of primary thyroid leiomyomas and leiomyosarcomas.
METHODS: One leiomyoma and four leiomyosarcomas arising within the thyroid gland were identified in the files of the Endocrine Tumor Registry of the Armed Forces Institute of Pathology. Histologic and immunohistochemical features were reviewed and follow-up obtained.
RESULTS: The patients included 2 females, ages 56 and 64 years, and 3 males, ages 45, 68, and 83 years. The patients presented with a mass in the thyroid gland that had increased in size over a number of months. All the tumors originated within a single lobe of the thyroid gland and measured from 1.1 to 9 cm in greatest dimension. Histologically, there was a fascicular pattern of growth comprised of spindle-shaped cells with blunt-ended nuclei. The leiomyoma was encapsulated, cytologically bland, and amitotic; the leiomyosarcomas were invasive with increased cellularity, pleomorphism, a high mitotic rate, necrosis, and hemorrhage. Immunohistochemical staining showed reactivity with vimentin, smooth muscle actin, muscle specific actin, and desmin. The patient with the leiomyoma was alive without evidence of disease 11 years after the initial presentation, with surgical resection as the only treatment. Three of the patients with leiomyosarcomas were dead within 2 years of diagnosis, in spite of aggressive therapeutic intervention. The remaining patient was still alive 10 months after initial presentation with multiple lung metastases.
CONCLUSIONS: Smooth muscle tumors of the thyroid gland are distinctive tumors. Leiomyosarcomas can be distinguished from anaplastic carcinoma, although patient outcome is uniformly unfavorable.
PubMed ID: 9028371
Article Size: 1 MB

Primary thyroid teratomas: a clinicopathologic study of 30 cases.

Thompson LD, Rosai J, Heffess CS.
Cancer. 2000 Mar 1;88(5):1149-58.
BACKGROUND: Primary thyroid teratomas are rare thyroid gland neoplasms of germ cell derivation that display features of trilineage differentiation.
METHODS: The histologic and immunophenotypic features of 30 cases of thyroid teratomas were reviewed, patient follow-up was obtained, and the results were analyzed statistically.
RESULTS: The patients included 15 females and 15 males ages newborn-56 years (mean, 12.4 years). All patients presented clinically with a mass in the thyroid, ranging in size from 2.0-13 cm in greatest dimension (mean, 6.0 cm). Histologically, the tumors usually were well circumscribed, although occasionally infiltrative into the thyroid parenchyma. Derivatives of all three germ layers (ectoderm, mesoderm, and endoderm) were present in varying degrees of maturity. The tumors were divided into benign (n = 7 tumors), immature (n = 14 tumors), and malignant (n = 9 tumors) as determined by an increasing percentage of tumor volume comprised of primitive mesenchymal or neural-type tissue. All the microscopically malignant tumors occurred in the adult population. Surgical excision was performed in 28 patients, followed by adjuvant therapy in 5 patients. Follow-up was obtained in 26 patients; 8 patients had died from or with tumor (5 neonates with immature histology and 3 adults with malignant histology; mean, 0.6 years) and 18 patients were alive with no evidence of disease at a mean of 16.9 years of follow-up.
CONCLUSIONS: Thyroid teratomas are rare neoplasms that can be divided into three types depending on the presence and proportion of the immature component. The outcome is dependent largely on the age of the patient, the size of the tumor at the time of initial presentation, and the presence and proportion of immaturity. Surgical excision is the treatment of choice, with adjuvant therapy reserved for the malignant cases. Copyright 2000 American Cancer Society.
PubMed ID: 10699906
Article Size: <1 MB

Renal cell carcinoma to the pancreas in surgical pathology material.

Thompson LD, Heffess CS.
Cancer. 2000 Sep 1;89(5):1076-88.
BACKGROUND: Clear cell carcinomas of the pancreas are rare and more likely represent metastatic renal cell carcinoma (RCC).
METHODS: Twenty-one cases of metastatic RCC to the pancreas were retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology. Histologic features were reviewed, special stains and immunohistochemical studies were performed, and patient follow-up data were obtained.
RESULTS: The patients included 9 women and 12 men ages 47-76 years (mean, 64.4 years). Patients experienced weight loss, abdominal pain, or a mass lesion. The tumors occurred anywhere within the pancreas. The mean size of the tumors was 4.0 cm. Histologically, the tumors were comprised of clear cells with a rich vascular network. The RCC was diagnosed before (n = 17 patients; ages up to 32.7 years) or after (n = 4 patients; ages up to 13.2 years) the pancreatic metastases were discovered. Surgery was used in all patients. Adjuvant chemotherapy was used in 4 patients. From the date of the diagnosis of pancreatic metastasis, 13 patients were dead with disseminated disease (DD) (mean, 4.5 years), and 8 patients were without disease (mean, 9.0 years). From the date of the diagnosis of primary RCC, 13 patients were DD (mean, 12.7 years), and 8 patients were without disease (mean, 24.7 years).
CONCLUSIONS: Although histochemical and immunohistochemical studies may help in the distinction between patients with primary versus metastatic clear cell tumors of the pancreas, clinical confirmation should be obtained. Surgical resection of the pancreatic metastatic disease is suggested, because the patient may still have a prolonged survival.
PubMed ID: 10964338
Article Size: 1 MB

Subacute (de Quervain’s) thyroiditis.

Thompson LD, Heffess CS.
Ear Nose Throat J. 2002 Sep;81(9):623.
FIRST PARAGRAPH: Subacute (de Quervain’s) thyroiditis is a seasonal disorder that generally affects middle-aged women. It is characterized by neck pain and generalized malaise, fatigue, fever, and chills following an upper respiratory infection, usually of viral etiology. Thyroid gland palpation elicits exquisite tenderness of the firm gland, which can be involved either focally or diffusely. The stage the disease determines whether there is hyper- or hypothyroidism.
PubMed ID: 12353438
Article Size: <1 MB

Thyroid gland follicular carcinoma.

Thompson LD.
Ear Nose Throat J. 2015 Mar;94(3):100-102.
FIRST PARAGRAPH: Thyroid gland follicular carcinoma is a malignant epithelial neoplasm of follicular cell differentiation that exhibits capsular and/or lymphovascular invasion while lacking the nuclear features of thyroid papillary carcinoma. While rarely inherited, follicular carcinoma will develop in about 20% of patients with Cowden syndrome, related specifically to PTEN germline mutations. Previous radiation exposure and iodine deficiency are known environmental etiologic factors.
PubMed ID: tbd
Article Size: <1 MB

Thyroid papillary carcinoma of columnar cell type: a clinicopathologic study of 16 cases.

Wenig BM, Thompson LD, Adair CF, Shmookler B, Heffess CS.
Cancer. 1998 Feb 15;82(4):740-53. — Comment in: Cancer. 1998 Dec 1;83(11):2421-3.
BACKGROUND: Thyroid papillary carcinoma of columnar cell type is considered an uncommon histologic subtype of papillary carcinoma characterized by its morphologic features and purportedly aggressive biologic course.
METHODS: Sixteen cases of thyroid papillary carcinoma of columnar cell type were identified from the Endocrine Tumor Registry at the Armed Forces Institute of Pathology and the Washington Hospital Center. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in 15 of the 16 cases.
RESULTS: Of the 16 cases reported, 13 patients were female and 3 were male. The ages ranged from 16-76 years (average, 47 years; median, 40 years). An asymptomatic neck mass was the most common clinical presenting symptom. Macroscopically, the tumors varied from circumscribed or encapsulated to infiltrative, ranging in size from 1.5-6.5 cm. Histologically, the tumors had diverse growth patterns, including papillary, solid, microfollicular, and cribriform. A common pattern was the presence of markedly elongated follicles arranged in parallel cords. Colloid-filled follicles could be found, at least focally, in all cases. The characteristic histologic appearance included the presence of elongated cells showing nuclear stratification. Other features included the presence of vacuolated-appearing cells, spindle-shaped cells, and squamoid nests. Limited areas in the tumors showed morphologic features typical of thyroid papillary carcinoma. In 14 of the cases, the tumor was encapsulated, showed limited invasive growth, or was a microscopic tumor. In two of the cases, there was extrathyroidal invasion. Immunohistochemical studies showed consistent reactivity with cytokeratin and vimentin; varied reactivity with thyroglobulin, epithelial membrane antigen, carcinoembryonic antigen, and LeuM1; and no reactivity with calcitonin or chromogranin. Treatment was by surgical resection; supplemental radioactive iodine therapy was administered in eight patients. Follow-up was available for all patients, 13 of whom (81%) were alive and free of disease or had died of unrelated causes over periods ranging from 2-11 years (average, 5.8 years). All 13 of these patients had tumor confined completely to the thyroid gland. One patient died 4 months after diagnosis secondary to sepsis. Two patients (17%) had aggressive biologic courses. In both patients there was extrathyroidal invasion. One of these patients died of metastatic disease to the lungs 3 years after diagnosis; the other was alive with bilateral pulmonary metastases 9 years after the diagnosis.
CONCLUSIONS: The findings of the current study indicate that thyroid papillary carcinoma of columnar cell type is a distinct morphologic type but not a distinct clinical type of thyroid papillary carcinoma. The biologic behavior of this tumor is predicated on clinical stage, with the presence or absence of extrathyroidal invasion being the single most important parameter. Treatment of patients with these tumors should be based on the clinical stage and not on the morphologic appearance.
PubMed ID: 9477108
Article Size: 3 MB

Undifferentiated thyroid carcinoma.

Thompson LD.
Ear Nose Throat J. 2013 Oct-Nov;92(10-11):500-4.
FIRST PARAGRAPH: Histologically, undifferentiated thyroid carcinomas show a variety of patterns, from sheet-like, storiform, fascicular, angiomatoid, and meningothelial to solid, exhibiting extensive lymph-vascular invasion.
PubMed ID: 24170460
Article Size: <1 MB

Ectopic sphenoid sinus pituitary adenoma (ESSPA) with normal anterior pituitary gland: A clinicopathologic and immunophenotypic study of 32 cases with a comprehensive review of the English literature.

Thompson LD, Seethala RR, Müller S.
Head Neck Pathol. 2012 Mar;6(1):75-100.
Ectopic sphenoid sinus pituitary adenoma (ESSPA) may arise from a remnant of Rathke’s pouch. These tumors are frequently misdiagnosed as other neuroendocrine or epithelial neoplasms which may develop in this site (olfactory neuroblastoma, neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, paraganglioma, melanoma). Thirty-two patients with ESSPA identified in patients with normal pituitary glands (intact sella turcica) were retrospectively retrieved from the consultation files of the authors’ institutions. Clinical records were reviewed with follow-up obtained. An immunohistochemical panel was performed on available material. Sixteen males and 16 females, aged 2-84 years (mean, 57.1 years), presented with chronic sinusitis, headache, obstructive symptoms, and visual field defects, although several were asymptomatic (n = 6). By definition, the tumors were centered within the sphenoid sinus and demonstrated, by imaging studies or intraoperative examination, a normal sella turcica without a concurrent pituitary adenoma. A subset of tumors showed extension into the nasal cavity (n = 5) or nasopharynx (n = 9). Mean tumor size was 3.4 cm. The majority of tumors were beneath an intact respiratory epithelium (n = 22), arranged in many different patterns (solid, packets, organoid, pseudorosette-rosette, pseudopapillary, single file, glandular, trabecular, insular). Bone involvement was frequently seen (n = 21). Secretions were present (n = 16). Necrosis was noted in 8 tumors. The tumors showed a variable cellularity, with polygonal, plasmacytoid, granular, and oncocytic tumor cells. Severe pleomorphism was uncommon (n = 5). A delicate, salt-and-pepper chromatin distribution was seen. In addition, there were intranuclear cytoplasmic inclusions (n = 25) and multinucleated tumor cells (n = 18). Mitotic figures were infrequent, with a mean of 1 per 10 HPFs and a <1% proliferation index (Ki-67). There was a vascularized to sclerotic or calcified stroma. Immunohistochemistry highlighted the endocrine nature of the tumors, with synaptophysin (97%), CD56 (91%), NSE (76%) and chromogranin (71%); while pan-cytokeratin was positive in 79%, frequently with a dot-like Golgi accentuation (50%). Reactivity with pituitary hormones included 48% reactive for 2 or more hormones (plurihormonal), and 33% reactive for a single hormone, with prolactin seen most frequently (59%); 19% of cases were non-reactive. The principle differential diagnosis includes olfactory neuroblastoma, neuroendocrine carcinoma, melanoma, and meningioma. All patients were treated with surgery. No patients died from disease, although one patient died with persistent disease (0.8 months). Surgery is curative in the majority of cases, although recurrence/persistence was seen in 4 patients (13.8%). In conclusion, ESSPAs are rare, affecting middle aged patients with non-specific symptoms, showing characteristic light microscopy and immunohistochemical features of their intrasellar counterparts. When encountering a tumor within the sphenoid sinus, ectopic pituitary adenoma must be considered, and pertinent imaging, clinical, and immunohistochemical evaluation undertaken to exclude tumors within the differential diagnosis. This will result in accurate classification, helping to prevent the potentially untoward side effects or complications of incorrect therapy.
PubMed ID: 22430769
Article Size: 4 MB

Diffuse hyperplasia of thyroid gland (Graves’ disease)

Thompson LDR.
Ear Nose Throat J. 2007 Nov;86(11):666-7.
FIRST PARAGRAPH: Widely known by its eponym Graves’ disease, diffuse hyperplasia of the thyroid gland is an autoimmune condition in which excess thyroid hormone production is unchecked by the normal feedback loop between the thyroid and the pituitary gland. The immune-system abnormality is mediated by antibodies to the thyrotropin receptor found on follicular epithelial cells. When the most specific antibody, known as thyroid-stimulating immunoglobulin (TSI), is bound to the thyrotropin receptor, the TSI mimics the action of pituitary thyrotropin and stimulates the follicular epithelium to produce hormone. The clinical effect of this autoimmune process is (1) thyrotoxicosis accompanied by diffuse thyroid enlargement and an infiltrative ophthalmopathy and (2) a spectrum of the systemic effects of excessive thyroid hormone production.
PubMed ID: 18225623
Article Size: <1 MB

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma.

Su HK, Wenig BM, Haser GC, Rowe ME, Asa SL, Baloch Z, Du E, Faquin WC, Fellegara G, Giordano T, Ghossein R, LiVolsi VA, Lloyd R, Mete O, Ozbek U, Rosai J, Suster S, Thompson LD, Turk AT, Urken ML.
Thyroid. 2016 Apr;26(4):512-7.
BACKGROUND: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases.
METHODS: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE.
RESULTS: The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE.
CONCLUSIONS: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists’ interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.
PubMed ID: 26953223
Article Size: <1 MB

Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.

Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA.
JAMA Oncol. 2016 Aug 1;2(8):1023-9.
IMPORTANCE: Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.
OBJECTIVE: To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
DESIGN, SETTING, AND PARTICIPANTS: International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
MAIN OUTCOMES AND MEASURES: Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
RESULTS: Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.
CONCLUSIONS AND RELEVANCE: Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
PubMed ID: 27078145

Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment

Thompson, LD.
Mod Pathol. 2016 Jul;29(7):698-707.
Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or 43 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).
PubMed ID: 27102347
Article Size: <1 MB

A Clinicopathologic Series of 685 Thyroglossal Duct Remnant Cysts

Thompson LD, Herrera HB, Lau SK.
Head Neck Pathol. 2016 May 9. [Epub ahead of print]
The clinical features of thyroglossal duct remnant cysts (TGDC) have been well described, however the histopathologic aspects of these lesions have not been addressed in a detailed manner. In particular, there has been no large community practice based series evaluating TGDC histologically compared with management outcomes. A retrospective review of all TGDC diagnosed between 2005 and 2015 was performed. Six hundred eighty-five patients were identified (344 males; 341 females). Age at presentation was bimodal (first and fifth decades) and ranged from 0.8 to 87 years (mean 31.3 years). Males predominate in children (150:111); females in adults (230:194). Patients presented most frequently with a mobile midline neck mass in an infrahyoid location. An associated skin fistula (n = 67) was twice as common in pediatric as adult patients. The average cyst size was 2.4 cm (range 0.4-9.9 cm) by imaging studies and 2.6 cm (range 0.2-8.5 cm) by pathologic examination; pediatric patients had smaller cysts (mean 2.1 cm) than adults (mean 2.8 cm). Histologically, 257 (38 %) TGDC were lined by respiratory epithelium alone, 68 (10 %) squamous epithelium alone, 347 (51 %) exhibited both respiratory and squamous epithelium, and 13 (1 %) had no identifiable epithelial lining. Four hundred eighty-four (71 %) TGDC had associated thyroid gland tissue present within the cyst wall (n = 282), skeletal muscle (n = 71), adipose tissue (n = 34), or a combination of these sites (n = 97). The hyoid bone was identified in 647 (grossly and/or histologically), and absent in 38. Surgical management consisted of Sistrunk procedure (n = 647), cystectomy (n = 31), or thyroidectomy/thyroid lobectomy (n = 7). Treatment related complications were observed in 6 patients, which included vocal cord damage, seroma, and hematoma. Recurrences developed in 20 (3 %) patients, 14 of whom were managed initially by cystectomy. Papillary thyroid carcinoma was identified in 22 (3.2 %) TGDC. In summary, TGDC show a bimodal peak in the 1st and 5th decades, commonly presenting as a midline cervical lesion below the hyoid bone, associated with a skin fistula in 10 %. Histologically TGDC are most commonly lined by a combination of respiratory and squamous epithelium. Thyroid gland tissue is identified in 71 % of cases (0.45 cm mean size), although not limited to the cyst wall, but present in the surrounding soft tissues. Rare TGDC may harbor malignancy (3.2 %). TGDC are most effectively managed by Sistrunk procedure rather than excision, which carries low rates of complications (1 %) and recurrence (3 %).
PubMed ID: 27161104
Article Size: 2.7 MB