Sinonasal carcinomas.

Head & Neck, Sinonasal Tract
Thompson LDR.
Curr Diag Pathol 2006 12, 40–53.
Malignant neoplasms of the sinonasal tract encompass a wide variety of epithelial, lymphoid and mesenchymal tumours. The separation and classification of epithelial or neuroepithelial tumours is sometimes challenging, especially when treatment and prognosis are different. Squamous cell carcinoma, keratinizing or non-keratinizing and, usually, the poorly differentiated type need to be separated from sinonasal undifferentiated carcinoma, lymphoepithelial carcinoma, neuroendocrine carcinoma and olfactory neuroblastoma. Whereas melanoma and lymphoma are also included in the broad differential, along with primitive neuroectodermal tumours and rhabdomyosarcomas, the focus of this commentary will be to present the major clinical, radiographical, histological, immunohistochemical, ultrastructural and molecular features which allow for separation of the principle mucosal epithelial neoplasms of the sinonasal tract.
PubMed ID: n/a
Article Size: 2 MB

Polymorphous low grade adenocarcinoma.

Head & Neck, Salivary Gland
Thompson LDR.
Pathol Case Rev 2004;9:259-263.
Polymorphous low-grade adenocarcinomas are minor salivary gland neoplasms with a predilection for intraoral sites. Women are affected twice as frequently as men, and generally present in the fifth to sixth decade of life with a painless ihaoral mass. The palatal mass is, on average, about 2 cm in greatest dimension. The tumors are submucosal, identified below an intact mucosa as a well-circumscribed although unencapsulated mass. The tumor is characterized by a polymorphous growth pattern, with individual tumors demonstrating multiple patterns, including solid, ductal-tubular, cribriform, trabecular, and single-file growth. Neurotropism is common, frequently forming a central nidus around which a “targetoid” pattern is formed. The neoplastic cells are isomorphic, containing round to oval vesicular nuclei with small nucleoli. Mitotic activity and necrosis are inconspicuous. There is frequently a slate gray-blue stroma separating the tumor cells. Immunohistochemical analysis demonstrates reactivity with cytokeratin, vimentin, S-100 protein, CD117, glial fibrillary acidic protein, and actin. Bcl-2 is overexpressed and there is generally a low proliferation index as determined by Ki-67 reactions. The tumor must be separated from pleomorphic adenoma (benign mixed tumor) and adenoid cystic carcinoma. Complete surgical excision will yield a more than 95% 10-year survival, although persistence or recurrence can emerge often in about 10% of patients more than 10 years later.
PubMed ID: n/a
Article Size: 4.9 MB

Pheochromocytoma.

Adrenal, Endocrine
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

Parotid Gland Nodular Fasciitis: A Clinicopathologic Series of 12 Cases with a Review of 18 Cases from the Literature.

Head & Neck, Salivary Gland
Gibson TC, Bishop JA, Thompson LD.
Head Neck Pathol. 2015 Sep;9(3):334-44.
Nodular fasciitis (NF), very uncommon in the parotid gland, is a benign myofibroblastic proliferation that may be mistaken for other neoplastic proliferations. The mass-like clinical presentation and histologic features result in frequent misclassification, resulting in inappropriate clinical management. There are only a few reported cases in the English literature. Cases within the files of the authors’ institutions (retrospective) confined to the parotid gland were compared to cases reported in the English literature (Medline 1966–2014). The patients included five females and seven males, aged 11–70 years (mean 45.2 years). All patients presented with a mass lesion, present on average 1.9 months, without a documented history of trauma. The lesions were 0.7–5.2 cm (mean 2.2 cm). Seven patients had fine needle aspiration. The majority of the lesions were circumscribed (n = 9), composed of spindle-shaped to stellate myofibroblasts (MF) arranged in a storiform growth pattern, juxtaposed to hypocellular myxoid tissue-culture-like areas with extravasation of erythrocytes. Dense, keloid-like collagen (n = 7) and occasional giant cells were seen (n = 6). Mitotic figures (without atypical forms) were readily identifiable (mean 4/10 HPFs). By immunohistochemical staining, the MF were reactive with vimentin, actins, and calponin, while the histiocytes were reactive with CD68. All patients had surgical excision. One patient developed local recurrence (12 months later). All were alive and disease free at last follow-up, with a mean 133 months of follow-up. The principle differential diagnoses include fibrosarcoma, fibromatosis, pleomorphic adenoma, myoepithelioma, neurofibroma, schwannoma, solitary fibrous tumor, leiomyoma, fibrous histiocytoma and myxoma. NF of the parotid gland occurs in middle-aged patients who present with a mass (mean 2.2 cm) in the parotid gland of short duration (1.9 months). FNA misinterpretation frequently leads to excision. Separation from myoepithelial and mesenchymal lesions affecting the parotid gland results in appropriate management.
PubMed ID: 25472697
Article Size: 3.7 MB
 
 
 
 

Parathyroid carcinoma occurring in multiple endocrine neoplasia type 1.

Endocrine, Parathyroid
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
 

Incisional or core biopsies of salivary gland tumours: how far should we go?

Head & Neck, Salivary Gland
Nelson BL, Thompson LDR.
Diagnostic Pathology Volume 18:9 September 2012 pages 358-365.
Trends in the evaluation of salivary gland masses have changed as imaging studies have improved and sampling techniques have evolved over the past several decades. Whether clinically palpable or detected by imaging studies, salivary gland masses have been readily evaluated by fine needle aspiration. More recently, imaging guided core-needle biopsy has been employed with mixed results. The literature on these techniques is reviewed and analyzed with particular attention to tissue adequacy and diagnostic accuracy. Comparison is made using selected case presentations to highlight the advantages and disadvantages of establishing a diagnosis when core-needle biopsy is utilized. Core-needle biopsy of salivary gland tumours may be a useful first diagnostic approach as long as the limitations of the procedure are well understood and managed.
PubMed ID: n/a
Article Size: <1 MB

Exophytic and papillary squamous cell carcinoma of the larynx.

Head & Neck, Larynx
Kardon DE, Thompson LDR.
Pathol Case Rev 2000;5(4):196-199.
Conventional squamous cell carcinoma (SCC) of the larynx presents as a largely flat or ulcerated lesion and is usually categorized histologically as in situ, superficially invasive, or deeply invasive. Papillary and exophytic squamous cell carcinomas of the larynx represent uncommon but distinct subtypes of SCC. As implied by their designations, these tumor types show predominant papillary or exophytic growth in the form of finger-like or filiform and broad-based bulbous fronds, respectively. Both tumor types are composed of cytologically malignant squamous epithelium. The following case illustrates the clinical and pathologic features of papillary squamous cell carcinoma and emphasizes the importance of distinguishing this entity from conventional squamous cell carcinoma of the larynx.
PubMed ID: n/a
Article Size: 2.5 MB

Endoscopic Management of Recurrent Anterior Skull Base Schwannoma

Head & Neck, Sinonasal Tract
Lee J, Thompson L, Garg R, Keschner D, Shibuya T.
International Journal of Otolaryngology and Head & Neck Surgery, Vol. 2 No. 2, 2013, pp. 52-56.
Objectives: Sinonasal schwannomas account for less than 4% of head and neck schwannomas, with the primary treatment modality being surgical excision via external approaches. The aim of this report is to present a rare case of recurrent schwannoma of the ethmoid cavity involving the anterior skull base which was successfully managed with endoscopic resection. Study Design: Case report and review of the literature. Methods: The clinical presentation, radiographic features, histopathologic characteristics, surgical approach, and patient outcome were examined in the context of a literature review. Results: A 43-year-old woman presented with a 9-month history of left facial pain and pressure. She had a prior history of sinonasal schwannoma excision with cerebrospinal fluid (CSF) leak repair via bifrontal craniotomy in 2007. Magnetic resonance imaging (MRI) and nasal endoscopy revealed a left ethmoid mass measuring 2.2 cm × 2.7 cm × 2.4 cm abutting the anterior skull base. The tumor was completely removed using a transnasal endoscopic approach, and the anterior skull base reconstructed with tensor fascia lata graft. Histology of the specimen showed schwannoma, and there has been no evidence of tumor recurrence nor CSF leak after 24 months of follow-up. Conclusion: With continual advances in surgical technique and instrumentation, sinonasal schwannomas have become increasingly more amenable to endoscopic resection even in the case of recurrence and skull base involvement.
PubMed ID: n/a
Article Size: >1 MB

BOOK REVIEW: ‘Biopsy Interpretation of the Upper Aerodigestive Tract and Ear’ by Edward B. Stelow, Stacey E. Mills.

Articles, Medical Techniques
Thompson LD.
Am J Surg Pathol. 2013 Oct;37(10):1632.
FIRST PARAGRAPH OF REVIEW: A fan of the Biopsy Interpretation series, I was pleased to review a new title, although without reviewing the first edition. As advertised, ‘recent advances in our understanding of aerodigestive tract pathology,’ are presented in a userfriendly manner, incorporating selected and targeted use of ancillary techniques to help reach a diagnosis, although the reader is reminded to focus on the standard hematoxylin and eosin-stained material first and foremost. In fact, the entire chapter on hematopathology only has a single immunohistochemistry image, which is normally a field run amok by mmunohistochemistry stains. Always forward thinking, and utilizing all resources available to reach a diagnosis, the book itself will be as helpful as any of the supporting ancillary studies.
PubMed ID: n/a
Article Size: <1 MB

Clinicopathologic and Immunophenotypic Characterization of 25 Cases of Acinic Cell Carcinoma with High-Grade Transformation

Head & Neck, Salivary Gland
Thompson LD, Aslam MN, Stall JN, Udager AM, Chiosea S, McHugh JB
Head Neck Pathol. 2016 Jun;10(2):152-60.
Acinic cell carcinoma (AiCC) with high-grade transformation is a rare variant of AiCC composed of both a conventional low-grade (LG) AiCC and a separate highgrade (HG) component. We describe here, the clinicopathologic and immunohistochemical features of 25 cases diagnosed between 1990 and 2015. Available tissue was analyzed and compared with a cohort of pure LG AiCC for the morphologic and immunophenotypic profile. Incidence was higher in females (1.8:1) than males with an overall mean age at presentation of 63.2 years. All tumors occurred in the parotid gland including 76 % with facial nerve trunk and branches involvement. Most patients were treated with extensive resection and adjuvant therapy. Local recurrence or distant metastasis occurred in most patients, with 72.7 % dead with disease (mean 2.9 years) and 3 patients alive with disease (mean 2.4 years). The majority of the tumors were composed of a LG microcystic AiCC and a HG component consisting of invasive lobules of undifferentiated cells with predominantly solid, cribriform, and glandular patterns. Acinic differentiation was still present in HG areas but aggressive features such as perineural invasion (76 %), lymphovascular invasion (62 %), positive margins (72 %), high mitotic rate, atypical mitoses and/or comedonecrosis (86 %) were easily identified. Compared to the pure LG AiCC, the cases with HG transformation showed significantly increased expression of cyclin-D1, p53 and Ki-67. Most HG areas of AiCC expressed membranous b-catenin (92 %) and were negative for p63 (three cases were focally positive), S100, SMA, androgen, and estrogen receptors. DOG1 expression was present in all LG AiCC tested with retained expression in 91 % of cases with HG transformation, supporting acinic differentiation in the HG foci. Recognition of AiCC with high-grade transformation is imperative as more aggressive clinical management is warranted.
PubMed ID: 26245749
Article Size: 6 MB
 
 
 
 

Evaluation of PAX2 and PAX8 Expression in Salivary Gland Neoplasms.

Head & Neck, Salivary Gland
Butler RT, Alderman MA, Thompson LD, McHugh JB.
Head Neck Pathol. 2015 Mar;9(1):47-50.
PAX2 and PAX8 are transcription factors involved in embryogenesis that have been utilized as immunohistochemical indicators of tumor origin. Specifically, PAX2 is a marker of neoplasms of renal and müllerian origin, while PAX8 is expressed by renal, müllerian, and thyroid tumors. While studies examining these transcription factors in a variety of tumors have been published, data regarding their expression in salivary gland neoplasms are limited. The goal of this study was to assess expression of PAX2 and PAX8 in a large cohort of salivary gland tumors. Utilizing tissue microarrays, samples of normal salivary glands (n = 68) and benign and malignant salivary gland neoplasms (n = 442) were evaluated for nuclear immunoreactivity with PAX2 and PAX8. No expression was observed with either marker in the normal salivary glands, and PAX8 was negative in all neoplasms. Focal expression of PAX2 was observed in one example each of oncocytoma and acinic cell carcinoma. These results indicate that evaluation of PAX2 and/or PAX8 expression would be valuable in differentiating primary salivary gland tumors from metastases known to express PAX2 and/or PAX8.
PubMed ID: 24771139
Article Size: <1 MB
 

Salivary Duct Carcinoma: The Predominance of Apocrine Morphology, Prevalence of Histologic Variants, and Androgen Receptor Expression

Head & Neck, Salivary Gland
Williams L, Thompson LD, Seethala RR, Weinreb I, Assaad AM, Tuluc M, Ud Din N, Purgina B, Lai C, Griffith CC, Chiosea SI.
Am J Surg Pathol. 2015 May;39(5):705-13.
Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC.
PubMed ID: 25871467
Article Size: 1 MB
 
 
 
 

Adenoid cystic carcinoma of the head and neck — An update

Head & Neck, Salivary Gland
Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, Strojan P, Rinaldo A, Haigentz M Jr, Takes RP, Mondin V, Teymoortash A, Thompson LDR, Ferlito A.
Oral Oncol. 2015 Jul;51(7):652-661.
This article provides an update on the current understanding of adenoid cystic carcinoma of the head and neck, including a review of its epidemiology, clinical behavior, pathology, molecular biology, diagnostic workup, treatment and prognosis. Adenoid cystic carcinoma is an uncommon salivary gland tumor that may arise in a wide variety of anatomical sites in the head and neck, often with an advanced stage at diagnosis. The clinical course is characterized by very late recurrences; consequently, clinical follow-up should extend at least >15 years. The optimal treatment is generally considered to be surgery with postoperative radiotherapy to optimize local disease control. Much effort has been invested into understanding the tumor’s molecular biological processes, aiming to identify patients at high risk of recurrence, in hopes that they could benefit from other, still unproven treatment modalities such as chemotherapy or biological therapy.
PubMed ID: 25943783
Article Size: 2.6 MB
 

Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma.

Head & Neck, Sinonasal Tract
Bishop JA, Thompson LD, Cardesa A, Barnes L, Lewis JS Jr, Triantafyllou A, Hellquist H, Stenman G, Hunt JL, Williams MD, Slootweg PJ, Devaney KO, Gnepp DR, Wenig BM, Rinaldo A, Ferlito A.
Head Neck Pathol. 2015 Dec;9(4):507-18.
Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed.
PubMed ID: 25757816
Article Size: 3.8 MB
 
 
 
 

Cherubism.

Head & Neck, Oral Cavity/Gnathic (Jaw)
Thompson LD.
Ear Nose Throat J. 2015 Jan;94(1):22-4.
FIRST PARAGRAPH: Cherubism is an autosomal-dominant inherited disease with variable expression. It is characterized by a progressive, painless, and symmetric expansion of the jaws. The disease is caused by a point mutation in the SH3BP2 gene (chromosome 4p16.3), which leads to dysregulation of the Msx-1 gene; this gene is involved in regulating mesenchymal interaction in craniofacial morphogenesis.
PubMed ID: 25606831
Article Size: <1 MB

Sox10 — A Marker for Not Only Schwannian and Melanocytic Neoplasms But Also Myoepithelial Cell Tumors of Soft Tissue: A Systematic Analysis of 5134 Tumors

Articles, Medical Techniques
Miettinen M, McCue PA, Sarlomo-Rikala M, Biernat W, Czapiewski P, Kopczynski J, Thompson LD, Lasota J, Wang Z, Fetsch JF.
Am J Surg Pathol. 2015 Jun;39(6):826-35.
Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
PubMed ID: 25724000
Article Size: 1.5 MB

Molecular Characterization of Apocrine Salivary Duct Carcinoma

Head & Neck, Salivary Gland
Chiosea SI, Williams L, Griffith CC, Thompson LD, Weinreb I, Bauman JE, Luvison A, Roy S, Seethala RR, Nikiforova MN.
Am J Surg Pathol. 2015 Jun;39(6):744-52.
Contemporary classification and treatment of salivary duct carcinoma (SDC) require its thorough molecular characterization. Thirty apocrine SDCs were analyzed by the Ion Ampliseq Cancer HotSpot panel v2 for mutations in 50 cancer-related genes. Mutational findings were corroborated by immunohistochemistry (eg, TP53, BRAF, ?-catenin, estrogen, and androgen receptors) or Sanger sequencing/SNaPshot polymerase chain reaction. ERBB2 (HER2), PTEN, FGFR1, CDKN2A/P16, CMET, EGFR, MDM2, and PIK3CA copy number changes were studied by fluorescence in situ hybridization. TP53 mutations (15/27, 56%), PTEN loss (11/29, 38%, including 2 cases with PTEN mutation), PIK3CA hotspot mutations (10/30, 33%), HRAS hotspot mutations (10/29; 34%), and ERBB2 amplification (9/29, 31%, including 1 case with mutation) represented the 5 most common abnormalities. There was no correlation between genetic changes and clinicopathologic parameters. There was substantial overlap between genetic changes: 8 of 9 cases with ERBB2 amplification also harbored a PIK3CA, HRAS, and TP53 mutation and/or PTEN loss. Six of 10 cases with PIK3CA mutation also had an HRAS mutation. These findings provide a molecular rationale for dual targeting of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways in SDC. FGFR1 amplification (3/29, 10%) represents a new potential target. On the basis of studies of breast carcinomas, the efficacy of anti-ERBB2 therapy will likely be decreased in SDC with ERBB2 amplification co-occurring with PIK3CA mutation or PTEN loss. Therefore, isolated ERBB2 testing is insufficient for theranostic stratification of apocrine SDC. On the basis of the prevalence and type of genetic changes, apocrine SDC appears to resemble one subtype of breast carcinoma-‘luminal androgen receptor positive/molecular apocrine.’
PubMed ID: 25723113
Article Size: <1 MB
 
 
 
 

Salivary duct carcinoma and the concept of early carcinoma ex pleomorphic adenoma

Head & Neck, Salivary Gland
Griffith CC, Thompson LD, Assaad A, Purgina BM, Lai C, Bauman JE, Weinreb I, Seethala RR, Chiosea SI.
Histopathology. 2014 Dec;65(6):854-60.
AIMS: The data on the histological type of carcinomatous component and the extent of extracapsular invasion for salivary carcinomas ex pleomorphic adenoma (PA) are conflicting. We aimed to determine the prognostic value of extracapsular invasion in salivary duct carcinomas (SDC) ex PA.
METHODS AND RESULTS: A total of 117 patients with SDC were identified retrospectively; 44 cases involving major salivary glands had pre-existing PA (44 of 117, 37%). The morphological spectrum of SDC ex PA was characterized. The primary endpoint was overall survival (OS). Most SDC ex PA were widely invasive at presentation (27 of 44; 61%). Five patients with intracapsular SDC ex PA experienced no disease progression. The assessment of extracapsular invasion was precluded in eight cases (e.g. positive margins of resection). The rate of lymph node involvement was similar in cases with extracapsular invasion of ?2 mm (two of three) and >7 mm (22 of 26). Only pT correlated with OS [116 months, 95% confidence interval (CI) 22-210 months for pT1 versus 20 months (95% CI 6-34) for pT4; P = 0.013].
CONCLUSIONS: Intracapsular SDC ex PA are potentially indolent. SDC ex PA with extracapsular invasion of ?2 mm are rare, and appear to be clinically aggressive. Several histological parameters preclude assessment of extracapsular invasion.
PubMed ID: 24804831
Article Size: <1 MB
 
 
 
 

Papillary Cystadenoma of Minor Salivary Glands: Report of 11 Cases and Review of the English Literature.Cases and Review of the English Literature.

Head & Neck, Salivary Gland
Tjioe KC, de Lima HG, Thompson LD, Lara VS, Damante JH, de Oliveira-Santos C.
Head Neck Pathol. 2015 Sep;9(3):354-9.
Papillary cystadenoma is a rare, benign salivary gland tumor which is well-circumscribed, containing cystic cavities with intraluminal papillary projections. Only 19 cases arising within minor salivary glands (MnSG) from the oral cavity sites have been reported in the English literature (PubMed 1958-2014). We report 11 new cases of MnSG papillary cystadenomas in conjunction with a review of the literature. Demographic information, clinical and histologic features, treatment and prognosis are compiled and discussed for all 30 cases reported in the English literature.
PubMed ID: 25547059
Article Size: 1.2 MB
 

Thyroid gland follicular carcinoma.

Endocrine, Thyroid
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: 25738712
Article Size: <1 MB

Sinonasal Tract Neurofibroma: A Clinicopathologic Series of 12 Cases with a Review of the Literature

Head & Neck, Sinonasal Tract
Azani AB, Bishop JA, Thompson LD.
Head Neck Pathol. 2015 Sep;9(3):323-33.
Neurofibroma (NF), a benign peripheral nerve sheath tumor, is very uncommon in the sinonasal tract, with only a few reported cases in the English literature. Cases within the files of the authors’ institutions confined to the sinonasal tract were compared to cases reported in the English literature (Medline 1966-2014). The 12 patients included 6 females and 6 males, aged 26-75 years (mean 46.2 years). The patients usually presented clinically with a mass lesion (n = 11), obstruction (n = 4) or pain (n = 3), with an average symptom duration of 42.9 months. Two patients had neurofibromatosis (NF1). Tumors involved the nasal cavity alone (n = 8), maxillary sinus alone (n = 2), or mixed sites (n = 2), with a range of 0.4-4.1 cm (mean 2.2 cm). The tumors were circumscribed, composed of spindled to wavy cells with curvilinear nuclei set in a background of collagenized stroma and mast cells. Nuclear palisading and perivascular hyalinization were not seen. Mitoses were scant. Pleomorphism, necrosis and increased cellularity were absent. By immunohistochemistry, the lesional cells were S100 protein, SOX10 and NFP positive, while CD34 highlighted the perineurium. INI1 was intact, with strong nuclear expression in all cases. All patients had surgical excision without recurrence (mean follow-up 8.6 years). The principle differential diagnoses include schwannoma, perineurioma, fibromatosis, and solitary fibrous tumor. NF of the sinonasal tract occurs in middleaged patients without a gender predilection, usually with non-specific symptoms present for a long duration. Tumors are relatively large (mean 2.2), and usually affect one site only. Surgery is curative, with only 16.7 % NF1 associated. S100 protein, SOX10 and NFP highlight the Schwann cells, with CD34 highlighting the perineural fibroblasts.
PubMed ID: 25503638
Article Size: 3.7 MB
 

Sinonasal tract mucosal melanoma.

Head & Neck, Sinonasal Tract
Thompson LD.
Ear Nose Throat J. 2014 Oct-Nov;93(10-11):E49-50.
FIRST PARAGRAPH: Mucosal melanoma is a neural-crest–derived neoplasm that originates in melanocytes and demonstrates melanocytic differentiation. Exposure to formalin and ultraviolet light are known etiologic factors; another possible factor is exposure to radiation. Approximately 15 to 20% of all skin melanomas develop on the head and neck, but less than 1% of all melanomas develop in ocular or mucosal sites, including the sinonasal tract.
PubMed ID: 25397394
Article Size: <1 MB

Functional Histology of Salivary Gland Pleomorphic Adenoma: An Appraisal.

Head & Neck, Salivary Gland
Triantafyllou A, Thompson LD, Devaney KO, Bell D, Hunt JL, Rinaldo A, Vander Poorten V, Ferlito A.
Head Neck Pathol. 2015 Sep;9(3):387-404.
The complex microstructure of salivary gland pleomorphic adenoma is examined in relation to function. Events related to secretion of macromolecules and absorption, responses to the altered microenvironment and controversies concerning epithelial-mesenchymal transition versus modified myoepithelial differentiation are explored. Their effects on tumor cell phenotypes and arrangements are emphasized. Heterotopic differentiation and attempts at organogenesis are also considered. The approach allows interpreting microstructure independently of histogenetic perceptions, envisaging the tumor cells as a continuum, endorsing luminal structures as the principal components, and defining pleomorphic adenoma as a benign epithelial tumour characterized by variable epithelial-mesenchymal transition, secretion/differentiation and metaplasia.
PubMed ID: 25380577
Article Size: 10.5 MB
 

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker.

Head & Neck, Sinonasal Tract
Lasota J, Felisiak-Golabek A, Aly FZ, Wang ZF, Thompson LD, Miettinen M.
Mod Pathol. 2015 May;28(5):715-20.
Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm with myoid phenotype (smooth muscle actin-positive), which distinguishes this tumor from soft tissue hemangiopericytoma/solitary fibrous tumor. Molecular genetic changes underlying the pathogenesis of glomangiopericytoma are not known. In this study, 13 well-characterized glomangiopericytomas were immunohistochemically evaluated for β-catenin expression. All analyzed tumors showed strong expression and nuclear accumulation of β-catenin. Following this observation, β-catenin glycogen serine kinase-3 beta phosphorylation region, encoded by exon 3, was PCR amplified in all cases and evaluated for mutations using Sanger sequencing. Heterozygous mutations were identified in 12 of 13 tumors. All mutations consisted of single-nucleotide substitutions: three in codon 32 (c.94G>C (n=2) and c.95A>T), four in codon 33 (two each c.98C>G and c.98C>T), two in codon 37 (c.109T>G), one in codon 41 (c.121A>G), and two in codon 45 (c.133T>C). At the protein level, these substitutions would lead to p.D32H, p.D32V, p.S33C, p.S33F, p.S37A, p.T41A, and p.S45L mutations, respectively. Previously, similar mutations have been reported in different types of cancers and shown to trigger activation of β-catenin signaling. All analyzed glomangiopericytomas showed prominent nuclear expression of cyclin D1, as previously shown for tumors with nuclear expression of β-catenin as a sign of oncogenic activation. These results demonstrate that mutational activation of β-catenin and associated cyclin D1 overexpression may be central events in the pathogenesis of glomangiopericytoma. In additon, nuclear accumulation of β-catenin is a diagnostic marker for glomangiopericytoma.
PubMed ID: 25431235
Article Size: <1 MB
 
 
 
 

Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: Clinical manifestations and prognostic significance.

Head & Neck, Larynx
Ferlito A, Rinaldo A, Bishop JA, Hunt JL, Poorten VV, Williams MD, Triantafyllou A, Devaney KO, Gnepp DR, Kusafuka K, Halmos GB, Westra WH, Takes RP, Thompson LDR
Eur Arch Otorhinolaryngol. 2016 Mar;273(3):533-6.
Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and nonmetastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.
PubMed ID: 25351497
Article Size: <1 MB
 

Novel PRKD Gene Rearrangements and Variant Fusions in Cribriform Adenocarcinoma of Salivary Gland Origin

Head & Neck, Salivary Gland
Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, Clarke BA, Skalova A, Chiosea SI, Seethala RR, Waggott D, Boutros PC, How C, Liu FF, Irish JC, Goldstein DP, Gilbert R, Ud Din N, Assaad A, Hornick JL, Thompson LD, Antonescu CR.
Genes Chromosomes Cancer. 2014 Oct;53(10):845-56.
Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with ‘mixed/indeterminate’ features. The RNAseq of 2 CAMSGs showed ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from ‘classic’ PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types.
PubMed ID: 24942367
Article Size: <1 MB
 
 
 
 

Spindle Cell Lipoma of the Tongue: A Clinicopathologic Study of 8 Cases and Review of the Literature.

Head & Neck, Oral Cavity/Gnathic (Jaw)
Lau SK, Bishop JA, Thompson LD.
Head Neck Pathol. 2015 Jun;9(2):253-9.
Spindle cell lipoma is a histologically distinct variant of lipoma characteristically arising in the subcutis of the posterior neck, upper back, or shoulder. Spindle cell lipomas infrequently occur within the oral cavity and, in particular, rarely involve the tongue. The clinical and pathologic features of eight cases of spindle cell lipoma affecting the tongue were analyzed. The study group included five men and three women ranging in age from 35 to 80 years (mean 57.4 years). Most lesions presented as either a painless or slowly growing lingual mass. The tumors were well circumscribed and characterized microscopically by a mixture of mature adipocytes, cytologically bland spindle cells, and interspersed bundles of thick collagen fibers in variable proportions. Myxoid stroma was a prominent feature in three lesions. The spindle cells were positive with CD34, while negative with S-100 protein, desmin, and smooth muscle actin. Treatment consisted of local excision in all cases. There have been no recurrences to date, with clinical follow up information available for all patients (range 11-118 months; mean 50.8 months). Lingual examples of spindle cell lipoma should be distinguished from other fat containing spindle cell neoplasms that can arise at this anatomic site.
PubMed ID: 25319950
Article Size: 2 MB
 

Keratocystic odontogenic tumor.

Head & Neck, Oral Cavity/Gnathic (Jaw)
Thompson LD.
Ear Nose Throat J. 2014 Sep;93(9):386-8.
FIRST PARAGRAPH: Keratocystic odontogenic tumor (KCOT; formerly known as odontogenic keratocyst) is a distinct developmental odontogenic cyst that may be locally aggressive and may be part of the nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome). Inherited as an autosomal dominant trait, there is high penetrance, although with variable expression, associated with loss of function of the PTCH gene (chromosome 9q22.3-q31), a tumor suppressor gene.
PubMed ID: 25255344
Article Size: <1 MB

Parathyroid adenoma.

Endocrine, Parathyroid
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

Chronic lymphocytic thyroiditis (Hashimoto thyroiditis).

Endocrine, Thyroid
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

Merkel cell carcinoma.

Other Anatomic Sites, Skin
Shiffer JD, Thompson LD.
Ear Nose Throat J. 2014 Mar;93(3):100-2.
FIRST PARAGRAPH: Merkel cell carcinoma is a rare and highly aggressive cutaneous neuroendocrine carcinoma that, in most cases, is caused by Merkel cell polyomavirus (approximately 80% of cases). The tumor usually arises on sun-exposed skin of elderly patients, particularly on the head and neck and extremities. There is a slight female preponderance and an increased risk in individuals who are immunosuppressed. Clinically, the tumors are often indistinguishable from other skin cancers and typically present as a firm, painless, rapidly growing nodule. They may be flesh-colored, red, or blue tumors that typically vary in size from 0.5 cm to more than 5 cm (average, 2 cm). When they have a reddish nodular appearance, they may be mistaken for angiosarcoma or granulation tissue.
PubMed ID: 24652557
Article Size: <1 MB

Canalicular Adenoma: A Clinicopathologic and Immunohistochemical Analysis of 67 Cases with a Review of the Literature

Head & Neck, Salivary Gland
Thompson LD, Bauer JL, Chiosea S, McHugh JB, Seethala RR, Miettinen M, Müller S.
Head Neck Pathol. 2015 Jun;9(2):181-95.
There is a lack of a comprehensive immunohistochemical (IHC) analysis of canalicular adenoma (CanAd), especially when combined with a description of the unique histologic features. Given the usual small biopsies, IHC may be useful in distinguishing CanAd from other tumors in the differential diagnosis. Retrospective. The patients included 54 females and 13 males (4.2:1), aged 43-90 years, with a mean age at presentation of 69.9 years. Clinical presentation was generally a mass (n = 61) slowly increasing in size (mean 38.5 months), affecting the upper lip (n = 46), buccal mucosa (n = 17) or palate (n = 4), involving the right (n = 29), left (n = 24) or midline (n = 9), without any major salivary gland tumors. The tumors ranged in size from 0.2 to 3 cm (mean 1.2 cm). Most tumors were multilobular or bosselated (76 %), often surrounded by a capsule. Histologically, the tumors were characterized by cystic spaces, tumor cords with beading, tubule formation, and by the presence of luminal squamous balls (n = 41). The cells were cuboidal to columnar with stippled chromatin. Mitoses were inconspicuous. A myxoid stroma (n = 64), sclerosis (n = 42), luminal hemorrhage (n = 51), and luminal microliths (calcifications) (n = 33) were characteristic. Nine (13.4 %) were multifocal. CanAd showed the following characteristic immunohistochemistry findings: CK-pan and S100 protein (strong, diffuse reaction); peripheral or luminal GFAP reaction; CK5/6 and p16 luminal squamous ball reaction; SOX10 nuclear reaction; cytoplasmic p63 reaction. CanAd are unique minor salivary gland tumors showing a distinct architecture and phenotype. They predilect to older women, with the majority multilobulated and affecting the upper lip, multifocal in 13 %; no major salivary gland tumors were identified. S100 protein, CK-pan, GFAP and SOX10 are positive, with luminal squamous balls highlighted by CK5/6 or p16.
PubMed ID: 25141970
Article Size: 4.5 MB
 
 
 
 

Oncocytic Lipoadenoma of the Salivary Gland: A Clinicopathologic Analysis of 7 Cases and Review of the Literature

Head & Neck, Salivary Gland
Lau SK, Thompson LD.
Head Neck Pathol. 2015 Mar;9(1):39-46.
Oncocytic lipoadenoma is an exceedingly uncommon neoplasm of the salivary gland composed of oncocytic epithelium and adipose tissue. Retrospective. Seven cases of oncocytic lipoadenoma were analyzed in order to further characterize the clinical and pathologic features of this rare tumor. The patients included six males and one female who ranged from 40 to 83 years of age (mean 62 years) at presentation. All tumors arose in the parotid gland. Grossly, the tumors were solitary, well circumscribed and had light brown to yellow cut surfaces. Histologically, the tumors were composed of an admixed population of oncocytes and adipocytes in varying proportions, with the lipomatous component ranging from 5 to 70 %. Other common features included the presence of serous acini, ductal elements, sebaceous glands, and a patchy chronic inflammation. Clinical follow up information, available in all cases, with a duration of 3-148 months (mean 57 months), showed no evidence of tumor recurrence. Due to its rarity, oncocytic lipoadenoma can pose problems in diagnosis, although the distinctive morphologic features of this neoplasm allow for separation from more commonly recognized oncocytic neoplasms of the salivary glands.
PubMed ID: 24737102
Article Size: 2.2 MB
 

Molecular diagnostic alterations in squamous cell carcinoma of the head and neck and potential diagnostic applications.

Head & Neck, Larynx
Hunt JL, Barnes L, Lewis JS Jr, Mahfouz ME, Slootweg PJ, Thompson LD, Cardesa A, Devaney KO, Gnepp DR, Westra WH, Rodrigo JP, Woolgar JA, Rinaldo A, Triantafyllou A, Takes RP, Ferlito A.
Eur Arch Otorhinolaryngol. 2014 Feb;271(2):211-23
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that continues to be difficult to treat and cure. In many organ systems and tumor types, there have been significant advances in the understanding of the molecular basis for tumorigenesis, disease progression and genetic implications for therapeutics. Although tumorigenesis pathways and the molecular etiologies of HNSCC have been extensively studied, there are still very few diagnostic clinical applications used in practice today. This review discusses current clinically applicable molecular markers, including viral detection of Epstein-Barr virus and human papillomavirus, and molecular targets that are used in diagnosis and management of HNSCC. The common oncogenes EGFR, RAS, CCND1, BRAF, and PIK3CA and tumor suppressor genes p53, CDKN2A and NOTCH are discussed for their associations with HNSCC. Discussion of markers with potential future applications is also included, with a focus on molecular alterations associated with targeted therapy resistance.
PubMed ID: 23467835
Article Size: <1 MB
 

The importance of histological types for treatment and prognosis in laryngeal cancer.

Head & Neck, Larynx
Ferlito A, Thompson LDR, Cardesa A, Gnepp DR, Devaney KO, Rodrigo JP, Hunt JL, Rinaldo A, Takes RP.
Eur Arch Otorhinolaryngol. 2013 Feb;270(2):401-3
FIRST PARAGRAPH: The classification of neoplasms is an important matter, with correlation of a tumor’s type with its biological behavior. To provide internationally acceptable criteria for the histological diagnosis of tumors, the World Health Organization (WHO) published an updated Pathology and Genetics of Head and Neck Tumours Classification of Tumours in 2005, which included tumors of the hypopharynx, larynx and trachea.
PubMed ID: 23315201
Article Size: <1 MB
 

Epstein-Barr virus and human herpes virus-8 are not associated with juvenile nasopharyngeal angiofibroma.

Head & Neck, Sinonasal Tract
Carlos R, Thompson LD, Netto AC, Pimenta LG, Correia-Silva Jde F, Gomes CC, Gomez RS.
Head Neck Pathol. 2008 Sep;2(3):145-9.
BACKGROUND: Nasopharyngeal angiofibroma (also known as juvenile nasopharyngeal angiofibroma) is a rare fibroblastic tumor with a vascular component that occurs in the nasopharynx and posterolateral nasal wall of adolescent boys. The etiology of nasopharyngeal angiofibroma remains elusive. This investigation was undertaken to determine if human herpes simplex virus-8 and Epstein-Barr virus are possible etiologic viruses and to determine if they have any association with the age of the patient and/or the proliferative state of the lesion.
MATERIALS AND METHODS: Formalin fixed, routinely processed, and paraffin embedded surgical specimens of 15 angiofibromas were submitted to PCR for EBV and HHV-8, while in situ hybridization was also employed for EBV. Immunohistochemical analysis for ki-67 was performed using MIB immunostaining.
RESULTS: None of the tumors were positive for HHV-8. The PCR technique produced a false positive reaction in five cases, with all cases non-reactive with EBV-ISH. The age of the patients did not show correlation with the Ki-67 labeling index.
CONCLUSION: Angiofibroma does not appear to be associated with either HHV-8 or EBV, thereby excluding these viruses as potential etiologic agents. The lack of a correlation between the proliferative index and the age of the patient suggests the proposed puberty induced, testosterone-dependent tumor growth may not play a significant role in tumor development.
PubMed ID: 20614308
Article Size: <1 MB
 

Intradural, extramedullary spinal cord granular cell tumor: a case report and clinicopathologic review of the literature.

Neuro (brain), Other Anatomic Sites
Weinstein BJ, Arora T, Thompson LD.
Neuropathology. 2010 Dec;30(6):621-6.
Granular cell tumor (GCT) of the spine is uncommon, with intradural extramedullary location being exceptionally rare. The non-specific clinical presentation and variable histologic patterns can make recognition of this tumor challenging. Two previous reports of GCT of the spine were reviewed (Medline 1960-2009) and analyzed with respect to this case report. The patients included two women and one man (mean age, 28.7 years). Patients presented with 3 to 4 months of lower back pain and/or lower extremity radiculopathy. The lesions appeared radiographically to be intradural and extramedullary or intramedullary. The tumors were found at T10 or L1-L2 space. Radiographically, all tumors enhanced homogenously on T1 post-gadolinium imaging with a mean tumor size of approximately 1.6 cm. Histologically, the tumors were composed of large, polygonal granular cells. The abundant cytoplasm was fine or coarsely granular, surrounding small, pale-staining nuclei, which were eccentrically located in the cell. The tumor cells were periodic acid Schiff positive, diastase resistant, and were positive with S-100 protein, CD68, inhibin, and neuron-specific enolase immunohistochemistry. The clinical and histologic differential diagnosis includes schwannoma, neurofibroma, meningioma, astrocytoma, melanocytoma, and metastatic tumors. Patients were managed with excision. One patient had symptomatic and radiographic local recurrence that was subsequently treated with radiation, resulting in stabilization of disease and symptoms. Intradural GCTs of the spine are rare and radiographically indistinguishable from tumors that more commonly arise in this location. Histologic recognition of this rare tumor is important because the subsequent clinical course of the disease differs from other similar lesions.
PubMed ID: 20113407
Article Size: 1 MB
 

Middle ear adenomas stain for two cell populations and lack myoepithelial cell differentiation.

Ear & Temporal Bone, Head & Neck
Lott Limbach AA, Hoschar AP, Thompson LD, Stelow EB, Chute DJ.
Head Neck Pathol. 2012 Sep;6(3):345-53.
Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.
PubMed ID: 22623086
Article Size: 1 MB
 

Oral Alveolar Soft Part Sarcoma in Childhood and Adolescence: Report of Two Cases and Review of Literature.

Head & Neck, Oral Cavity/Gnathic (Jaw)
Argyris PP, Reed RC, Manivel JC, Lopez-Terrada D, Jakacky J, Cayci Z, Tosios KI, Pambuccian SE, Thompson LD, Koutlas IG.
Head Neck Pathol. 2013 Mar;7(1):40-9.
Alveolar soft part sarcoma (ASPS) constitutes a rare soft tissue malignant neoplasm comprising less than 1 % of all soft tissue sarcomas. ASPS demonstrates a strong predilection for adolescents and young adults, with a female predominance reported. The head and neck region is the most commonly affected region in pediatric patients with the tongue and orbit affected most commonly. Herein we present the clinical, radiographic, histopathologic, immunohistochemical and molecular features of two examples of ASPS affecting the oral cavity of 4 and 13 year-old boys, along with a focused review of the literature on intraoral ASPS in pediatric patients.
PubMed ID: 22961078
Article Size: <1 MB
 

Prognostic biological features in neck dissection specimens.

Head & Neck, Oropharynx
Woolgar JA, Triantafyllou A, Lewis JS Jr, Hunt J, Williams MD, Takes RP, Thompson LD, Slootweg PJ, Devaney KO, Ferlito A.
Eur Arch Otorhinolaryngol. 2013 May;270(5):1581-92.
The superior prognostic value offered by routine histopathological staging of neck dissections, as compared to clinical staging using palpation and modern imaging techniques, is well established in the literature concerning the management of squamous cell carcinoma of the head and neck. In this review, we discuss the definitions and criteria used in standardised routine histopathological reporting and explore additional potential nodal prognostic features. In addition, we critically appraise the value of immunohistochemistry, histochemistry, molecular and other non-morphological techniques and suggest tumour and host features that merit further investigations.
PubMed ID: 22983222
Article Size: 1 MB
 

Oral lichen planus.

Head & Neck, Sinonasal Tract
Thompson LD.
Ear Nose Throat J. 2012 Mar;91(3):102-4.
FIRST PARAGRAPHS: The cause of lichen planus is not known. Its treatment depends on the specific type–reticular, erosive, or bullous–and usually includes topical or systemic corticosteroids and topical antifungal agents. Patients require lifelong monitoring and/or therapy. Lichen planus (LP) is a chronic, self-limited, inflammatory disorder of unknown etiology that involves mucous membranes, skin, nails, and hair. It is postulated that there is an abnormal T-cell-mediated immune response that results in disruption of the basement membrane. Several drugs are known to be associated with the onset of LP, but the exact mechanism is unknown.
PubMed ID: 22430334
Article Size: MB

Paranasal sinus mucocele.

Head & Neck, Sinonasal Tract
Thompson LD.
Ear Nose Throat J. 2012 Jul;91(7):276-8.
FIRST PARAGRAPHS: Radiographic findings are essential to the diagnosis of paranasal sinus mucocele. Usually opacification of the sinus with thinning, erosion, or destruction of the sinus wall are seen. Mucocele of the paranasal sinuses is a distinct clinicopathologic entity in which there is obstruction of the sinus cavity outflow tract, resulting in expansion of the sinus walls. The histologic features are quite nonspecific, requiring clinical, radiologic, and pathologic correlation. Most of these lesions result from increased pressure in the sinus due to sinus outlet obstruction, usually as a consequence of inflammatory or allergic processes. However, tumor, trauma, and previous surgery may play a role.
PubMed ID: 22829031
Article Size: <1 MB

Salivary duct carcinoma.

Head & Neck, Salivary Gland
Thompson LD.
Ear Nose Throat J. 2012 Sep;91(9):356-9.
FIRST PARAGRAPH: Salivary duct carcinoma is a high-grade adenocarcinoma that resembles breast ductal carcinoma. It is believed to be derived from intra- and interlobular excretory ducts. Salivary duct carcinoma may arise de novo or as a relatively common malignant component of a carcinoma ex pleomorphic adenoma. It accounts for about 9% of all malignant salivary gland tumors. Although there is a wide age range at presentation, most patients present in the seventh decade of life; men are affected much more frequently than women (4:1).
PubMed ID: 22996706
Article Size: <1 MB

Sinonasal Tract Adenoid Cystic Carcinoma Ex-Pleomorphic Adenoma: A Clinicopathologic and Immunophenotypic Study of 9 Cases Combined with a Comprehensive Review of the Literature.

Head & Neck, Sinonasal Tract
Toluie S, Thompson LD.
Head Neck Pathol. 2012 Dec;6(4):409-21.
Primary sinonasal tract carcinoma ex-pleomorphic adenoma (CEPA) is very uncommon, with adenoid cystic carcinoma (ACC) CEPA exceptional. These tumors are often misclassified. This is a retrospective study. Nine cases of ACC CEPA included 7 females and 2 males, aged 39-64 years (mean, 51.1 years). Patients presented most frequently with obstructive symptoms (n = 5), epistaxis (n = 3), nerve changes or pain (n = 3), present for a mean of 25 months (men: 9.5 versus women: 29.4 months; p = 0.264). The tumors involved the nasal cavity alone (n = 5), nasopharynx (n = 2), or a combination of locations (n = 2) with a mean size of 2.9 cm (females: 3.3; males: 1.7; p = 0.064). Most patients presented at a low clinical stage (n = 7, stage I), with one patient each in stage II and IV, respectively. Histologically, the tumors showed foci of PA associated with areas of ACC. Tumors showed invasion (lymph-vascular: n = 4; perineural: n = 6; bone: n = 6). The neoplastic cells were arranged in tubules, cribriform and solid patterns, with peg-shaped cells arranged around reduplicated basement membrane and glycosaminoglycan material. Mitoses ranged from 0 to 33, with a mean of 8.7 mitoses/10 HPFs. Necrosis (n = 2) and atypical mitotic figures (n = 1) were seen infrequently. Immunohistochemical studies showed positive reactions for cytokeratin, CK5/6, p63, CK7, EMA, SMA, calponin, S100 protein and CD117, several highlighting luminal versus basal cells components. GFAP, CK20 and MSA were non-reactive. p53 and Ki-67 were reactive to a variable degree. Surgery (n = 8), accompanied by radiation therapy (n = 5) was generally employed. Five patients developed a recurrence, all of whom died with disease (mean, 8.4 years), while 4 patients are either alive (n = 2) or had died (n = 2) without evidence of disease (mean, 15.9 years). In summary, ACC CEPA probably arises from the minor mucoserous glands of the upper aerodigestive tract, usually presenting in patients in middle age with obstructive symptoms in a nasal cavity based tumor. Most patients present with low stage disease (stage I and II), although invasive growth is common. Recurrences develop in about a 55 % of patients, who experience a shorter survival (mean, 8.4 years) than patients without recurrences (mean, 15.9 years). The following parameters, when present, suggest an increased incidence of recurrence or dying with disease: bone invasion, lymph-vascular invasion, and perineural invasion.
PubMed ID: 22941242
Article Size: 2.5 MB
 

Orbital infantile myofibroma: a case report and clinicopathologic review of 24 cases from the literature.

Other Anatomic Sites, Soft Tissue
Mynatt CJ, Feldman KA, Thompson LD.
Head Neck Pathol. 2011 Sep;5(3):205-15.
Isolated orbital infantile myofibroma are rare tumors in the head and neck. The mass-like clinical presentation and variable histologic features result in frequent misdiagnosis and potentially inappropriate clinical management. There are only a few reported cases in the English literature. Twenty-four patients with orbital infantile myofibroma or myofibromatosis were compiled from the English literature (Medline 1960–2011) and integrated with this case report. The patients included 14 males and 10 females, aged newborn to 10 years (mean, 34.8 months), who presented with a painless mass in the infra- or supraorbital regions, usually increasing in size andassociated with exophthalmos (n = 5). Females were on average older than their male counterparts (38.9 vs. 31.9 months, respectively; P = 0.71). The tumors were twice as frequent on the left (n = 16) than right (n = 8). Patients experienced symptoms for an average of 2.7 months before clinical presentation. The tumors involved the bone (n = 17) or the soft tissues (n = 7) of the orbit, with extension into the nasal or oral cavity (n = 3). The mean size was 3.0 cm, with a statistically significant difference between males and females (mean: 3.9 vs. 1.82; P = 0.0047), but without any differences based on age at presentation (P = 0.25), duration of symptoms (P = 0.66), or bone or soft tissue involvement (P = 0.51). Grossly, all tumors were wellcircumscribed, firm to rubbery, homogenous, and white– grey. Histologically, the tumors were biphasic, showing whorled and nodular areas of fusiform cells with extracellular collagen, mixed with a population of small, primitiveappearing, darkly staining cells. Necrosis was not present, but mitoses could be seen. Tumors with immunohistochemistry performed showed strong and diffuse smooth muscle actin and vimentin immunoreactivity, but were negative with muscle specific actin, desmin, MYOD1, myogenin, S100 protein, GFAP, keratin, CD31, 34, Factor VIIIR-Ag, and CD45RB. The principle histologic differential diagnosis includes juvenile hyaline fibromatosis, fibrous hamartoma of infancy, fibromatosis coli, leiomyoma, infantile hemangiopericytoma, infantile fibrosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, and lymphoma. All patients were managed with surgery. Recurrences developed in two patients at 4 and 6 months, respectively. Follow-up data was available on all but two patients (n = 22). These patients were either alive without evidence of disease (n = 18), alive but with disease (n = 3), or had died unrelated to this disease (i.e., neuroblastoma, n = 1). Orbital infantile myofibroma is a rare tumor, presenting in infancy as an enlarging mass of the orbit, with characteristic histomorphologic and immunophenotypic features. Orbital disease is usually isolated rather than part of systemic disease, and shows an excellent long-term prognosis, making appropriate separation from other conditions important.
PubMed ID: 21512784
Article Size: 2.5 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.

Endocrine, Pituitary
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