Category Archives: Larynx

Thompson LD, Wieneke JA, Miettinen M, Heffner DK.

Am J Surg Pathol. 2002 Feb;26(2):153-70.

Laryngeal spindle cell (sarcomatoid) carcinomas are uncommon tumors, frequently misdiagnosed as reactive lesions or mesenchymal malignancies. The records of 187 patients with tumors diagnosed as laryngeal spindle cell (sarcomatoid) carcinoma were retrieved from the files of the Otorhinolaryngic Tumor Registry of the Armed Forces Institute of Pathology. There were 174 men and 13 women, 35-92 years of age (average, 65.6 years). Nearly all patients experienced hoarseness (n = 165 [88%] patients) for a mean duration of 11.0 months. Patients admitted to smoking (n = 162 [87%] patients) and/or alcohol use (n = 90 [48%] patients). Most tumors were glottic (n = 132 [71%]), T1 (n = 111 [59%]), 1 and polypoid (n = 185 [99%]), with a mean tumor size of 1.8 cm. Histologically, squamous cell carcinoma (n = 157 [84%]) was noted, ulcerated, and blended with the spindle cell component, which was most frequently arranged in a storiform pattern (n = 92 [49%] tumors). Foci of benign or malignant cartilage and/or bone (n = 13 [7%]) were noted in the spindle cell component. All patients were treated with surgery (n = 90 [48%] patients) or surgery with radiation (n = 97 [52%] patients). Recurrences developed in 85 (45%) patients. Overall, T1 glottic tumors managed by complete surgical eradication had the best outcome (mean follow-up, 7.8 years).

PubMed ID: 11812937

Article Size: <1 MB

 

Thompson LD, Gannon FH.

Am J Surg Pathol. 2002 Jul;26(7):836-51.

Chondrosarcomas of the larynx are rare tumors accounting for about 0.5% of all laryngeal primary tumors. A total of 111 laryngeal chondrosarcoma cases, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology. There was a 3.6:1 male/female ratio of patients 25-91 years of age (mean, 64.4 years). Patients presented most frequently with hoarseness (n = 72 patients) present for a mean of 28.2 months. The majority of tumors involved the cricoid cartilage (n = 77) with a mean size of 3.5 cm. All tumors were invasive and malignant by radiology and/or histology (into bone within the ossified laryngeal cartilages in 52 tumors). Most tumors were low-grade lesions: grade 1 (n = 51), grade 2 (n = 54); there were six grade 3 tumors. An associated benign chondroma with (n = 41 tumors) or without ischemia (n = 24 tumors) was noted. All patients had surgery and five had radiation therapy. Wide excision or voice-sparing surgery was used in 73 patients, whereas 37 patients had a laryngectomy. Recurrences occurred in 20 (18%) patients, 10 of whom underwent salvage laryngectomy. At the last follow-up, 102 patients had no evidence of disease (alive or dead, mean 11.2 years) and five patients had evidence of disease (alive, one patient, 6.5 years; dead, four patients, mean 6.4 years). The six patients with high-grade chondrosarcoma were all without disease at the last follow-up (mean, 15.1 years). There was no difference in clinical outcome based on grade (p = 0.210), location (p = 0.078), or treatment (p = 0.607) but was worse for patients with a myxoid-type chondrosarcoma (p = 0.044). Primary laryngeal chondrosarcomas are typically low- to moderate-grade lesions involving the cricoid cartilage, frequently associated with a chondroma. They usually portend an excellent overall long-term prognosis with initial conservative voice-sparing surgery.

PubMed ID: 12131151

Article Size: 1 MB

 

Thompson LD, Wenig BM, Heffner DK, Gnepp DR.

Otolaryngol Head Neck Surg. 1999 May;120(5):718-24.

Exophytic and papillary squamous cell carcinomas (SCCs) are uncommon variants of SCC of the upper aerodigestive tract mucosa. The histomorphologic distinction between these variants has not been previously attempted or correlated with prognostic outcome. One hundred four cases of exophytic and papillary SCCs of the larynx were identified in the files of the Armed Forces Institute of Pathology from 1971 to 1991. The patients included 25 women and 79 men, aged 27 to 89 years (average 60.7 years). Patients had hoarseness at presentation, and many patients were using tobacco (n = 87) and/or alcohol (n = 49). Tumors measured up to 6 cm in greatest dimension. The larger tumors were associated with vocal cord impairment (n = 39). Histologically, the SCCs were divided into 2 growth patterns: papillary-frond (n = 12) or broad-based, exophytic (n = 92). Patients were treated with excisional biopsy, vocal cord stripping, and/or laryngectomy, in conjunction with radiation therapy (n = 70). Eighty-seven patients had no evidence of disease at last follow-up (average follow-up 8.6 years). Seventeen patients with an exophytic pattern died with disease (10 disseminated disease; 7 local disease). No patients with papillary patterns died of disease, although there had been 4 recurrences. In conclusion, patients with papillary and exophytic SCCs have a better prognosis than those with conventional SCCs, and the prognosis for those with papillary SCCs is even better.

PubMed ID: 10229599

Article Size: <1 MB

 

Whaley RD, Thompson LDR.

Head Neck Pathol. 2021 Dec;15(4):1162-1171.

Laryngeal mesenchymal neoplasms are rare, with smooth muscle tumors comprising a small subset. Specifically, Epstein-Barr virus (EBV)-associated smooth muscle tumors are exceptionally rare, lacking a comprehensive evaluation of their clinical and histologic features. Two patients (a 59 year old male and 51 year old female) had received renal transplants 156 and 240 months, respectively prior to onset of laryngeal symptoms. Supraglottic polypoid masses were identified and removed conservatively. Histologically, the tumors were hypercellular, showing alternating light and dark areas, the latter composed of primitive appearing round cells, while a more characteristic spindled tumor cell population was noted in the remaining areas. Cytoplasmic vacuoles were noted adjacent to the nucleus. There was no tumor necrosis or pleomorphism, but increased mitotic figures (11-12/2 mm2) were seen, without atypical forms. The tumor cells were strongly immunoreactive with smooth muscle actin and smooth muscle myosin heavy chain and with Epstein-Barr virus encoded RNA (EBER) by in situ hybridization. These patients were reviewed in the context of a thorough English literature review, which demonstrates a wide age range at presentation without a sex predilection, but with most patients from specific ethnic groups (Chinese, Thai, Pilipino). Three-quarters of patients are part of multifocal disease and the majority are post-renal transplantation patients. Conservative management seems to yield the best overall outcome for these indolent tumors. In conclusion, EBV-associated smooth muscle tumors should be considered in any immunocompromised patient with a head and neck smooth muscle tumor, especially when EBER is documented by in situ hybridization. Conservative management may be employed, even when multifocal tumors are documented.

PubMed ID: 33891274

Article Size: 3 MB

Thompson, LDR.

Surg Pathol Clin. 2017 Mar;10(1):15-33.

Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

PubMed ID: 28153131

Article Size: 13 MB

 

Rodrigo JP, García-Pedrero JM, Suárez C, Takes RP, Thompson LD, Slootweg PJ, Woolgar JA, Westra WH, Brakenhoff RH, Rinaldo A, Devaney KO, Williams MD, Gnepp DR, Ferlito A.

Eur Arch Otorhinolaryngol. 2012 Apr;269(4):1073-83

Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions. We conducted a thorough review of the published literature to identify those studies using biomarkers to predict malignant progression of laryngeal epithelial precursor lesions. Of the 336 studies identified in this systematic search, 15 met the inclusion criteria and form the basis of this review. Limited studies suggest that certain biomarkers are potentially reliable predictors of malignant progression including various regulators of cell adhesion and invasion (e.g. FAK, cortactin, osteopontin, and CD44v6) and proliferation-associated markers such as TGF-?RII and Kv3.4. The predictive value of these markers, however, has yet to be confirmed in large-scale prospective studies. Although the cell cycle-related proteins are the most frequently studied markers, none have been consistently reliable across multiple studies. The absence of standardization in methodologies, test interpretation, and other parameters may contribute to study inconsistencies. Various biomarkers have proved to have potential prognostic value and could be clinically relevant. The utility and prognostic power of these biomarkers should be confirmed in large, well-designed, standardized prospective studies.

PubMed ID: 22081098

Article Size: <1 MB

 

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

 

Coca-Pelaz A, Barnes L, Rinaldo A, Cardesa A, Shah JP, Rodrigo JP,, Suárez C,, Eloy JA, Bishop JA, Devaney KO, Thompson LD, Wenig BM, Strojan P, Hamoir M, Bradley PJ,, Gnepp DR,, Silver CE, Slootweg PJ, Triantafyllou A, Vander Poorten V,, Williams MD, Skálová A, Hellquist H, Teymoortash A, Medina JE, Robbins KT, Pitman KT, Kowalski LP, de Bree R, Mendenhall WM, Takes RP, Ferlito A.

Adv Ther. 2016 Apr;33(4):553-79.

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended.

PubMed ID: 27084720

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Chiesa-Estomba CM, Thompson L, Agaimy A, Zidar N, Simpson RHW, Franchi A, Rodrigo JP, Mäkitie AA, Almangush A, Leivo I, Ferlito A.

Virchows Arch. 2023 Oct;483(4):441-449.

Head and neck squamous cell carcinoma forms an anatomically and functionally complex group of malignancies. The signifcant local aggressiveness and frequent regional relapses motivate ongoing research to identify more reliable and sensitive prognostic and predictive biomarkers. One emerging area of cancer biology is the evaluation of tumor budding at the advancing invasive front of various types of epithelial cancers. Recent studies suggest that tumor budding is a relatively common phenomenon in cancer progression and that it may have important prognostic implications for patients due to its potential to provide valuable insights into the biology and clinical behavior of head and neck cancer. In this review, we aim to provide information about tumor budding in head and neck squamous cell carcinoma. Thus, we hope to shed light on the complex biology of these malignancies, as well as aiding diagnostic, classifcation, and better characterization and thereby, looking for new avenues for improving patient outcomes.

PubMed ID: 37642731

Article Size: <1 MB

Kerr DA, Thompson LDR, Tafe LJ, Jo VY, Neyaz A, Divakar P, Paydarfar JA, Pastel DA, Shirai K, John I, Seethala RR, Salgado CM, Deshpande V, Bridge JA, Kashofer K, Brčić I, Linos K.

Am J Surg Pathol. 2021 Dec 1;45(12):1707-1719.

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.

PubMed ID: 34001695

Article Size: <1 MB

Thompson LDR, Karamurzin Y, Wu ML, Kim JH.

Head Neck Pathol. 2008 Jun;2(2):67-74.

BACKGROUND: True mesenchymal, non-cartilaginous neoplasms of the larynx are rare. Extrapleural solitary fibrous tumor (SFT) is a localized neoplasm characterized by proliferation of thin-walled vessels and collagen-producing cells and is considered within the ‘hemangiopericytoma-solitary fibrous tumor’ spectrum. SFT primary in the larynx is exceptional.

DESIGN: Case report set in a comparison with other cases reported in the English literature (MEDLINE 1966 to 2007).

RESULTS: A 49-year old white male presented with difficulty breathing, progressive over the past 2 years. He denied dysphagia and weight loss. Past medical history was significant for asthma. He denied cigarette smoking or alcohol abuse. There were no cervical deformities on physical exam. Fiberoptic laryngoscopy was performed upon stabilization of respiratory function. A smooth, round, submucosal mass measuring 2.3 cm in greatest diameter arising from the inferior surface of left true vocal cord was causing near total obstruction of the endolaryngeal space. The mass was excised. The surface mucosa was intact and unremarkable. A cellular, spindle cell neoplasm was arranged in loose fascicles, associated with heavy collagen fiber deposition. The collagen was wiry and heavy. Cells were bland with cytoplasmic extensions. The nuclei were vesicular to hyperchromatic and elongated with inconspicuous nucleoli. Vessels were prominent and delicate, with patulous spaces. Mitotic figures were easily identified, but atypical forms were not present. The cells were strongly and diffusely immunoreactive with CD34 and bcl-2, while non-reactive with cytokeratin, EMA, actin, ALK-1, S100, desmin, and CD117. These findings confirmed a diagnosis of extraplural solitary fibrous tumor. Without further disease, the patient is alive without evidence of disease, 12 months after surgery. Conclusions The characteristic histologic pattern of solitary fibrous tumor can be noted in extrapulmonary locations. Development in the larynx is uncommon, but the tumor presents as a polypoid mass with characteristic histologic and immunophenotypic features. Conservative local excision is the treatment of choice to yield an excellent prognosis.

CONCLUSIONS: The characteristic histologic pattern of solitary fibrous tumor can be noted in extrapulmonary locations. Development in the larynx is uncommon, but the tumor presents as a polypoid mass with characteristic histologic and immunophenotypic features. Conservative local excision is the treatment of choice to yield an excellent prognosis.

PubMed ID: 20614325

Article Size: <1 MB

 

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

 

Thompson LD, Derringer GA, Wenig BM.

Mod Pathol. 2000 May;13(5):528-35.

Laryngeal amyloidosis (LA) is uncommon and poorly understood, with limited long-term clinicopathologic and immunophenotypic studies in the literature. Eleven cases of LA were retrieved from the files of the Otorhinolaryngic-Head & Neck Tumor Registry from 1953 to 1990. The histology, histochemistry, immunohistochemistry, and follow-up were reviewed. All patients (three women and eight men) presented with hoarseness at an average age of 37.8 years. The lesions, polypoid or granular, measured an average of 1.6 cm and involved the true vocal cords only (n = 4), false vocal cord only (n = 1), or were transglottic (n = 6). An acellular, amorphous, eosinophilic material was present in the stroma, often accentuated around vessels and seromucous glands, which reacted positively with Congo red. A sparse lymphoplasmacytic infiltrate was present in all cases that demonstrated light chain restriction by immunohistochemistry in three cases (kappa = 2, lambda = 1). Serum and urine electrophoreses were negative in all patients. Treatment was limited to surgical excision, including a single laryngectomy. Six patients manifested either recurrent and/or multifocal/systemic disease: two patients with light chain restriction were dead with recurrent disease (mean, 11.1 years); two patients were dead with no evidence of disease (mean, 31.7 years); and two patients were alive, one with light chain restriction and recurrent and multifocal disease (41.6 years) and one with no evidence of disease after a single recurrence (43.4 years). The remaining five patients were either alive or had died with no evidence of disease an average of 32.4 years after diagnosis. No patient developed multiple myeloma or an overt B-cell lymphoma. LA is an uncommon indolent lesion that may be associated with multifocal disease (local or systemic). The presence of an associated monoclonal lymphoplasmacytic infiltrate and recurrent/multifocal disease in the respiratory or gastrointestinal tract of a few cases and the lack of development of a systemic plasma cell dyscrasia or overt systemic B-cell malignancy suggest that some LA may be the result of an immunocyte dyscrasia or tumor of mucosa-associated lymphoid tissue.

PubMed ID: 10824924

Article Size: 1.5 MB

 

Loos BM, Wieneke JA, Thompson LD.

Laryngoscope. 2001 Jul;111(7):1197-202.

OBJECTIVE: Primary laryngeal angiosarcoma (LA) is rare without a reported series evaluating these tumors.

STUDY DESIGN/METHODS: Five patients with LA were retrospectively retrieved from the Otorhinolaryngic Registry of the Armed Forces Institute of Pathology.

RESULTS: Three men and 2 women, aged 29 to 71 years, presented with hoarseness (n = 4) and hemoptysis (n = 1). Two patients had previous neck radiation. The tumors involved the supraglottis (n = 4) with a mean size of 3.1 cm. Histologically, all tumors had anastomosing vascular channels lined by remarkably atypical endothelial cells protruding into the lumen, frequent atypical mitotic figures, and hemorrhage. All cases tested (n = 4) demonstrated immunoreactivity with antibodies to Factor VIII-RA and CD34. All patients had surgery followed by postoperative radiation (n = 3 patients). Three patients died with disease (mean, 17 mo), whereas one patient is alive with no evidence of disease at 18 years.

CONCLUSIONS: LA is a rare tumor, frequently associated with previous radiation, usually involving the supraglottis with characteristic histomorphologic and immunophenotypic features. LA has a poor prognosis, making appropriate separation from other conditions important.

PubMed ID: 11568541

Article Size: <1 MB

 

Wieneke JA, Gannon FH, Heffner DK, Thompson LD.

Mod Pathol. 2001 Dec;14(12):1209-15.

True giant cell tumors of the larynx (GCTL) are quite rare, and only individual case reports are documented in the literature. Eight cases of GCTL were identified in the Otorhinolaryngic Pathology Tumor Registry between 1966 and 2000. There were 2 women and 6 men, ages 26 to 62 years (mean, 44.5 yrs). Patients presented with a palpable neck mass (n = 5), airway obstruction (n = 3), hoarseness (n = 3), and dysphagia (n = 2). All tumors involved the thyroid cartilage, a few with local extension. The mean tumor size was 4.1 cm. Histologically, the tumors showed no connection to the surface epithelium and arose in sites of ossification. The tumors had an expansile, infiltrative growth and consisted of numerous multinucleated osteoclast-like giant cells within a cellular stroma composed of plump, oval mononuclear cells. Of interest was that the nuclei of the giant cells were similar to the nuclei of the stromal cells. Treatment included biopsy only with adjuvant therapy (n = 2), local resection (n = 3), and total laryngectomy (n = 3). Follow-up showed 5 patients were alive without evidence of disease (mean follow-up, 6.9 yrs); 2 died of unrelated causes (mean survival, 22.2 yrs). No patients developed recurrences. GCTL are rare tumors that can cause significant airway obstruction. Complete surgical resection yields an excellent outcome without adjuvant therapy.

PubMed ID: 11743042

Article Size: 2 MB

 

Fung EK, Neuhauser TS, Thompson LD.

Ann Diagn Pathol. 2002 Feb;6(1):61-6.

Primary larynx lymphomas, specifically of the mucosa-associated lymphoid tissue, are a rare but documented phenomenon. Transformation of any type of lymphoma that has the presence of Reed-Sternberg cells is unusual in lymph nodes and exceptional in extranodal sites. Herein, we report the first case (to the best of our knowledge in a review of the English literature [MEDLINE 1966-2001]) in which both of these unusual findings are present; that is, an extranodal marginal zone B-cell lymphoma of laryngeal mucosa-associated lymphoid tissue with Hodgkin-like transformation. The patient is a 78-year-old man who presented with intermittent shortness of breath, progressive dysphagia, and intermittent hoarseness. On examination, a large mass of the left supraglottic larynx was identified with a ‘ball-valve’ effect into the laryngeal inlet with inspiration. Examination of the neck showed no palpable masses. Histologic examination of the incisional biopsy showed replacement of the submucosa by sheets of atypical monocytoid B cells (CD20+, CD79a+, lambda+, CD3-) characterized by nuclear atypia, mitotic activity, plasmacytoid differentiation, and restricted for lambda light chains. Dutcher bodies were easily identified. Interspersed throughout the neoplastic lymphoid population were numerous Reed-Sternberg cells and variants immunoreactive for CD30 and CD15 and nonreactive for CD45RB. The patient was treated with 44 cGy to the neck and larynx and was alive and free of disease at last contact, 2.6 years after the original presentation.

PubMed ID: 11842381

Article Size: <1 MB

 

Garcia RE, Gannon FH, Thompson LD.

Laryngoscope. 2002 Jun;112(6):1015-8.

OBJECTIVES: To analyze the long-term clinical outcome of dedifferentiated chondrosarcoma or chondrosarcoma with additional malignant mesenchymal component (CAMMC) of the larynx and compare the results with those of axial chondrosarcomas.

STUDY DESIGN/METHODS: Two patients with CAMMC of the larynx (0.03%) were retrospectively identified within the archives of the Armed Forces Institute of Pathology between 1970 and 2001. We compared the clinical and histologic features of these two cases with those reported in the English literature (Medline 1966-2001) (Table I).

RESULTS: Patient no. 1 was a 67-year-old man who presented with a 12-month history of hoarseness and was found to have a 4-cm mass involving the cricoid cartilage. Enucleation was performed and histologically demonstrated a dedifferentiated chondrosarcoma. Without additional intervention, the patient died after 136 months without evidence of disease. Patient no. 2 was a 41-year-old man who also presented with a 12-month history of hoarseness and dysphagia and was found to have a 5-cm mass involving the cricoid cartilage. A total laryngectomy was performed for the dedifferentiated chondrosarcoma. He is alive without evidence of disease at last contact (91 mo).

CONCLUSION: CAMMC of the larynx are rare tumors but have a better prognosis than their axial counterparts (mean, 6 mo). Initial voice-sparing surgery can be followed with more aggressive surgery if recurrences develop.

PubMed ID: 12160266

Article Size: <1 MB

 

Hellquist H, Ferlito A, Mäkitie AA, Thompson LDR, Bishop JA, Agaimy A, Hernandez-Prera JC, Gnepp DR, Willems SM, Slootweg PJ, Rinaldo A.

Adv Ther. 2020 Jun;37(6):2667-2677. doi: 10.1007/s12325-020-01348-4. Epub 2020 Apr 23.

During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.

PubMed ID: 32329013

Article Size: <1 MB

Thompson LD.

Eur Arch Otorhinolaryngol. 1997;254(8):357-66.

There are a variety of diagnostically challenging lesions in the head and neck region. Contact ulcer usually occurs within specific clinical parameters (vocal abuse, post-intubation and gastro-esophageal reflux), which should be documented in correlation with the granulation tissue-like response affecting the posterior vocal cords. Spindle squamous cell carcinoma (carcinosarcoma) presents a variably cellular spindle cell proliferation, often with surface epithelial ulceration. The clinical presentation of a firm, polypoid mass in the larynx, combined with the histomorphologic features of a spindle cell tumor, can be confirmed to be of epithelial origin when a portion of the overlying epithelium is seen to blend with the spindle cell component, or when ancillary studies authenticate the epithelial origin of the tumor. The diagnosis of a verrucous squamous cell carcinoma can only be made accurately with an accurate clinical history. The very well differentiated histologic appearance, a broad pushing border of infiltration, a bland epithelial proliferation with scant mitotic activity and ‘church-spire’-type keratosis coupled with the clinical presentation of a large, locally destructive lesion, can confirm the diagnosis of verrucous carcinoma. A wide variety of disorders can result in midline destructive disease clinically, but a specific etiology must be sought to provide appropriate clinical management. Angiocentric T/NK-cell lymphoma of the sinonasal tract is one such disease. The atypical lymphoid cells are usually angiocentric and angiodestructive in their growth pattern. Identification of the atypical cells in the early stages of disease may be difficult, often requiring multiple biopsies over time with the application of immunohistochemical stains or molecular studies to accurately identify the nature of the infiltrate. Cystic squamous cell carcinoma in the neck is almost always a manifestation of metastatic tumor and not a brachiogenic carcinoma. When specific histomorphologic features are noted (a large, unfilled cyst lined by a ribbon-like or endophytic growth of a ‘transitional’-appearing squamous epithelium with a limited degree of anaplasia), most of these tumors demonstrate primaries in Waldeyer’s ring, often of a very small size. Adequate clinical work-up (pan-endoscopy, extensive radiographic imaging and random biopsies or prophylactic tonsillectomy) is mandatory in order to limit the radiation-therapy ports and to document the location of the primary, yielding an excellent long-term prognosis.

PubMed ID: 9332890

Article Size: <1 MB

 

Ferlito A, Haigentz M Jr, Bradley PJ, Suárez C, Strojan P, Wolf GT, Olsen KD, Mendenhall WM, Mondin V, Rodrigo JP, Boedeker CC, Hamoir M, Hartl DM, Hunt JL, Devaney KO, Thompson LD, Rinaldo A, Takes RP.

Eur Arch Otorhinolaryngol. 2014 Mar;271(3):425-34.

Despite remarkable advances in the care of patients with laryngeal cancer over the past several decades, including a growing awareness of therapeutic complications and attention to quality of life, little is known about the causes of mortality in this population. In addition to the laryngeal malignancy itself, acute and late or chronic treatment-associated causes, second primary cancers, intercurrent disease and psychosocial factors are all responsible for patient morbidity and mortality. We examine the current literature related to the causes of death in patients with laryngeal cancer, in the hope of guiding future interventions to improve the longevity and quality of life of individuals with this cancer.

PubMed ID: 23591796

Article Size: <1 MB

 

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):520S-521S. doi: 10.1177/0145561319890165.

FIRST PARAGRAPH: Inflammatory myofibroblastic tumor (IMT) is a distinctive, rarely metastasizing, (myo)fibroblastic neoplasm composed of spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and/or eosinophils. Genetically, most IMTs harbor tyrosine kinase fusions, usually the ALK gene with an ever-expanding list of partner genes (TIMP3-ALK is most common), although these rearrangements are rare in adults. More common in abdominal soft tissue and lung sites, head and neck tumors comprise about 20% of all IMTs. Children and young adults are usually affected, with a slight female predominance. Symptoms are nonspecific and generally related to obstructive symptoms due to mass effect. Patients are generally managed surgically, although molecular-targeted therapy (eg, crizotinib) shows good response. While metastatic disease is exceptional, local recurrences are seen in about 25% of patients.

PubMed ID: 31760795

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2004 Sep;83(9):609.

FIRST PARAGRAPH: Chondrosarcoma of the larynx accounts for approximately 0.2% of all head and neck malignancies and approximately 1% of all laryngeal malignant tumors, although it is the most common nonepithelial neoplasm of the larynx. Men are affected more frequently than women (3:1 ratio), usually during the middle to later decades of life. Patients present with a variety of symptoms as a result of tumor growth, including dyspnea, dysphagia, hoarseness, airway obstruction, and/or pain.

PubMed ID: 15529643

Article Size: <1 MB

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

Thompson L.

Ear Nose Throat J. 2006 May;85(5):304.

FIRST PARAGRAPH: Both infectious and inflammatory conditions can result in laryngitis, which is divided into acute and chronic forms. Some conditions are more frequent in adults, while others are more common in children. Laryngitis (‘croup,’ epiglottitis, and laryngotracheobronchitis) has many causes, including viral, bacterial, mycotic, or mycobacterial infections, trauma, neoplasms, vascular compromise during surgery, iatrogenic injury from feeding tubes or tracheostomy tubes, foreign-body impaction, and radiation therapy. A number of etiologies may be present synchronously, such that an infection may develop in association with radiation therapy, for example. Therefore, multiple etiologies may need to be addressed.

PubMed ID: 16771019

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2009 Mar;88(3):824-5.

FIRST PARAGRAPH: Granular cell tumors, also called Abrikossoff tumors, are benign, slowly growing neoplasms, presumably of Schwann cell origin. They may occur anywhere in the body, although 50% occur in the head and neck. The most common site is the tongue; the larynx is involved in approximately 10% of all cases. Granular cell tumors typically develop in the fourth and fifth decades of life; they are quite rare in children. Blacks are affected more commonly than other races. A slight female preponderance has been reported. As many as 10% of patients experience multifocal synchronous or metachronous tumors.

PubMed ID: 19291628

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2011 May;90(5):214-6.

FIRST PARAGRAPH: Spindle cell squamous cell carcinoma (SCSCC) is a squamous cell carcinoma (SCC) with a biphasic appearance, yielding a spindle cell transformation. Many names have been used in the past, but the terminology used here highlights the spindled and squamous cell appearance. As with all cases of upper aerodigestive tract SCC, there is a strong association with smoking and alcohol abuse. Furthermore, radiation exposure is occasionally reported in patients with SCSCC. This SCC variant accounts for approximately 2 to 3% of all laryngeal tumors. Men are affected much more frequently than women (12:1 ratio), and the incidence peaks in the seventh decade of life.

PubMed ID: 21563088

Article Size: <1 MB

Thompson L.

Ear Nose Throat J. 2007 Jul;86(7):379

FIRST PARAGRAPH: Squamous papilloma (SP) is the most common benign laryngeal tumor. It is caused by the human papillomavirus. Clinically, SP rarely occurs as a solitary lesion; most arise as multiple, recurrent tumors, usually in children. SPs generally originate in the true and false vocal folds; they may spread to other sites in the oral cavity and aerodigestive tract. They form at the juxtaposition of the squamous and respiratory epithelia. If an area of juxtaposition is artificially induced (such as by squamous metaplasia), spread of the disease may result. There is a characteristic bimodal age distribution, with a juvenile peak at 5 years and an adult peak between 20 and 40 years. The disease course tends to be more aggressive in children, who frequently develop recurrent and progressive disease. The relatively small diameter of the airways in children may account for some of the severe respiratory embarrassment they experience. There is a slight male predominance in adults. Patients usually present with dysphonia and hoarseness.

PubMed ID: 17702311

Article Size: <1 MB

Akst LM, Thompson LD.

Ear Nose Throat J. 2003 Nov;82(11):844-5.

FIRST PARAGRAPH: Amyloidosis is a benign accumulation of extracellular, insoluble, fibrillar protein. In general, the deposition of amyloid may be either localized or systemic and either primary or secondary. Laryngeal amyloidosis is rare, accounting for less than 1% of all benign laryngeal tumors. When it does occur, it is commonly localized and primary. Multifocal disease is present in up to 15% of patients. The disease typically manifests as hoarseness or vocal changes in the fifth to sixth decades, and it affects men and women equally.

PubMed ID: 14661432

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2005 Jun;84(6):340.

FIRST PARAGRAPH: A larynx contact ulcer, also known as a pyogenic granuloma, is a benign lesion that is most common among adult men. Patients present with hoarseness and/or throat pain, and they often experience chronic throat-clearing or habitual coughing. Contact ulcer is associated with vocal abuse, intubation, and acid regurgitation. Intubation-induced contact ulcer is more common among females, especially in an emergent setting when an inappropriately sized endotracheal tube has been placed. Gastrolaryngeal reflux or gastroesophageal reflux disease (GERD) is frequently missed because physicians do not correlate the nonspecific gastric symptoms with the laryngeal symptoms. A hiatal hernia, peptic esophagitis, or gastritis can cause acid reflux, usually during sleep, thereby leading to the development of a contact ulcer without the cause being obvious to the patient.

PubMed ID: 16075851

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2013 Sep;92(9):426-8.

FIRST PARAGRAPHS: Nodules usually affect the anterior to middle thirds of the true vocal folds, and they are nearly always bilateral. About 1.5% of the overall population suffers from hoarseness; among the most common causes of hoarseness are vocal fold nodules and polyps. Vocal fold nodules and polyps represent reactive changes of the laryngeal mucosa and adjacent stroma that result in benign nodular or polypoid growths. Their etiology is multifactorial, but vocal misuse is one of the most common causes, followed by infection, smoking, and hypothyroidism. Extroverts are more likely to develop nodules and polyps.

PubMed ID: 24057901

Article Size: <1 MB

 

Thompson LD.

Ear Nose Throat J. 2016 Jul;95(7):262-6.

FIRST PARAGRAPH: Neuroendocrine neoplasms of the larynx encompass five separate tumors: paraganglioma, typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. Many synonyms are employed, with well-, moderately, and poorly differentiated neuroendocrine carcinoma commonly applied to the middle three tumors (World Health Organization preferred terminology). Paraganglioma is an exceedingly uncommon neuroendocrine tumor in the larynx, as is large cell neuroendocrine carcinoma, and therefore these will not be further discussed.

PubMed ID: 27434472

Article Size: <1 MB

Penner CR, Thompson LD.

Ear Nose Throat J. 2003 Jun;82(6):427.

FIRST PARAGRAPH: Tracheopathia osteoplastica (tracheobronchopathia osteochondroplastica) is a segmental degenerative disorder of the tracheobronchial tree. It is characterized by multiple submucosal cartilaginous and osseous nodules of various sizes that cause a narrowing of the upper respiratory tract. This disorder is most common in elderly men, and it is occasionally associated with chronic inflammation or with trauma. Tracheopathia osteoplastica can manifest clinically as nonspecific signs and symptoms, although stridor and dyspnea are common. Radiologic studies may suggest the diagnosis if scalloped nodular calcified opacities are seen in the submucosa. The diagnosis is confirmed after endoscopic and pathologic examination.

PubMed ID: 12861866

Article Size: <1 MB

College of American Pathologists (CAP)

Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis. Mucosal malignant melanoma is included. Lymphomas and sarcomas are not included.

Based on AJCC/UICC TNM, 7th edition
Protocol web posting date: October 2009
Protocol effective date: January 2010

Article Size: 1 MB

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