Category: H&amp;N Case Review

2023-01-05

3:58 pm

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parotid, salivary

Head & Neck Case Review

January, 2023

History

A 61-year-old female presents with an enlarging mass along the left angle of the mandible and pre-auricular area. A contrast-enhanced CT scan of the neck shows a heterogeneous, irregular left preauricular mass involving the parotid gland and invading into facial skin.

Images

Quiz

1. Which of the following immunohistochemical stains is MOST likely to be positive in this carcinoma?

A. p40
B. Androgen receptor
C. S-100 protein
D. Estrogen receptor

2. Which of the following is TRUE?

A: This carcinoma is most likely to arise in the minor salivary glands.
B: This carcinoma only arises as carcinoma ex pleomorphic adenoma.
C: This carcinoma is most common in female patients.
D: This carcinoma can show ERBB2 gene amplification.

Diagnosis

Salivary duct carcinoma with squamous cell and sarcomatoid components

Salivary duct carcinoma is an epithelial malignancy that can occur de novo or as the malignant component in a carcinoma ex pleomorphic adenoma. This type of neoplasm accounts for approximately 10% of salivary gland neoplasms and most commonly arises in the parotid gland. Salivary duct carcinoma classically presents in elderly males in the sixth and seventh decades as a rapidly growing tumor usually with associated facial nerve paralysis. Several histological subtypes have been described including: micropapillary, sarcomatoid, mucinous, basal-like, and oncocytic. However, mixed cell types are very rare. The most frequent genetic alterations include mutations in TP53 (55%), HRAS (23%), PIK3CA (23%), amplification of ERBB2 (35%), PTEN deletion, and BRAF mutations.

Histologically, salivary duct carcinoma resembles high-grade ductal carcinoma of the breast. Architecturally, the tumor cells in salivary duct carcinoma form large ducts with comedonecrosis, cribriforming, and Roman-bridge-like features (Figures 2 and 3). Cytologically, tumor cells have apocrine and oncocytic features with abundant, eosinophilic cytoplasm and round nuclei with vesicular chromatin and prominent nucleoli. Nuclear pleomorphism and mitotic figures are common. When salivary duct carcinoma has a mixed cell type such as sarcomatoid (Figure 4), the components are usually distinct, but a transition zone may be present. Squamous cell carcinoma mixed with salivary duct carcinoma has been very rarely described (Figures 2 and 5).

Classically, the majority of salivary duct carcinomas stain positive for androgen receptor. As seen in our case of a mixed cell type carcinoma, immunohistochemistry shows distinct staining in the salivary duct carcinoma and squamous cell components (Figures 6 and 7). The salivary duct carcinoma component is strongly and diffusely positive for androgen receptor and almost totally negative for p40, while the squamous cell carcinoma component is strongly and diffusely positive for p40 and negative for androgen receptor. Salivary duct carcinoma is one of the most aggressive types of salivary gland carcinoma with a median overall survival of 69 months and a disease specific survival of 64% from a large SEER analysis. Subtypes, including the sarcomatoid subtype, aren’t clearly associated with worse outcomes, but the clinical significance of this extremely rare mixed squamous cell carcinoma component is unknown.

References

WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; forthcoming. (WHO classification of tumours series, 5th ed.; vol. 9). https://publications.iarc.fr.
Hardy N, Thompson J, Mehra R, Drachenberg CB, Hatten K, Papadimitriou JC. Parotid Salivary Duct Carcinoma With a Prominent Squamous Component: Immunohistochemical Profile, Diagnostic Pitfalls, and Therapeutic Implications. Int J Surg Pathol. 2021;29(7):726-730.
Kusafuka K, Kawasaki T, Onitsuka T, Hamaguchi N, Morita K, Mukaigawa T, Nishiya Y, Kamijo T, Iida Y, Nakajima T, Sugino T. Acantholytic Squamous Cell Carcinoma and Salivary Duct Carcinoma Ex-pleomorphic Adenoma of the Submandibular Gland: A Report of Two Extremely Rare Cases with an Immunohistochemical Analysis. Head Neck Pathol. 2020;14(1):230-238.
Nagao T, Gaffey TA, Serizawa H, Iwaya K, Watanabe A, Yoshida T, Yamazaki K, Sageshima M, Lewis JE. Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases with review of the literature. Am J Clin Pathol. 2004;122(2):222-31.
Williams L, Thompson LD, Seethala RR, Weinreb I, Assaad AM, Tuluc M, Ud Din N, Purgina B, Lai C, Griffith CC, Chiosea SI. Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression. Am J Surg Pathol. 2015; 39(5):705-13.
Jayaprakash V, Merzianu M, Warren GW, Arshad H, Hicks WL Jr, Rigual NR, Sullivan MA, Seshadri M, Marshall JR, Cohan DM, Zhao Y, Singh AK. Survival rates and prognostic factors for infiltrating salivary duct carcinoma: Analysis of 228 cases from the Surveillance, Epidemiology, and End Results database. Head Neck. 2014;36(5):694-701

Quiz Answers

Q1 = B. Androgen receptor

Q2 = D. This carcinoma can show ERBB2 gene amplification

Contributors

Stephanie Hart, MD
PGY-1, Department of Pathology, Microbiology and Immunology
Vanderbilt University Medical Center

James S. Lewis Jr. MD
Professor
Associate Director of Surgical Pathology
President, North American Society of Head and Neck Pathology
Vanderbilt University Medical Center

Head & Neck Case Review 2022-09

2022-09-01

2:39 pm

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neck

Head & Neck Case Review

September, 2022

History

A 72-year-old female presents with hoarseness of voice and dysphagia. A 3.2 x 1.9 x 2.7 cm heterogenous nodule in the left neck adjacent to the submandibular gland is noted on ultrasound. An ultrasound guided core needle biopsy is performed.

Images

Link to Virtual Slide HERE!

Quiz

1. Which of the following is TRUE?

A. These tumors are defined by PAX8::GLIS3 gene rearrangements.
B. These tumors are typically driven by mutations in the succinate dehydrogenase complex.
C. Sclerosis is a key feature to predict aggressive (i.e. metastatic) potential.
D. They often show low and high molecular weight cytokeratin expression.

2. TRUE or FALSE: 10% of these tumors are familial/inherited.

Diagnosis

Head and neck (parasympathetic) paraganglioma with sclerosis

Head and neck paragangliomas are neuroendocrine tumors that typically arise from parasympathetic ganglia in the head and neck region. They show a female predilection and appear to be driven by chronic hypoxia as evidenced by a higher prevalence in populations living at higher altitudes. The most common head and neck site is the carotid body (60%), followed by the middle ear (i.e. jugulotympanic, 30%), vagus nerve (10%), larynx (<1%), and thyroid (rare reports).

Head and neck paragangliomas are most often clinically non-functional and typically present as asymptomatic, often palpable masses, but vagal tumors may rarely (<1%) secrete catecholamines. Jugulotympanic tumors characteristically present with pulsatile tinnitus, while laryngeal paragangliomas may be accompanied by hoarseness. Carotid body tumors classically demonstrate horizontal mobility on palpation but vertical fixation (Fontaine sign), presumably due to their close association with the carotid artery.

Preoperative core needle and fine needle aspirate biopsies are typically not indicated for head and neck paragangliomas and should in fact be avoided when suspected clinically or radiologically, since these procedures pose rare but significant dangers given their vascularity and proximity to vital structures such as the carotid artery.

When resected, paragangliomas grossly show an ovoid or fusiform appearance and may be variably adherent to adjacent structures. Jugulotympanic tumors are notably ill-defined and may show bone and cavernous sinus invasion. Cut surfaces are highly vascular and may range from a homogeneous tan/brown to a more fibrous white. Prior infarction/embolization may impart a more variegated appearance.

Histologically, paragangliomas are well-demarcated but often uncircumscribed, and may infiltrate adjacent tissues. The classic growth pattern consists of organoid (Zellballen) cellular nests composed of chief cells with a granular amphophilic or eosinophilic cytoplasm surrounded by a thin layer of spindled sustentacular cells and embedded in a highly vascular stroma. The nuclei show a “salt-and-pepper” type chromatin as well as random nuclear size variation typical of many neuroendocrine tumors. Tumor cells are characteristically positive for neuroendocrine markers such as INSM1, synaptophysin, and chromogranin, but almost invariably negative for cytokeratins. Notably, GATA3 expression may be variably expressed in paragangliomas. Sustentacular cells are highlighted by S100 or SOX-10. Head and neck paragangliomas, especially those of the carotid body, are prone to considerable sclerosis which then imparts a corded “pseudoinfiltrative” appearance.

The morphologic differential diagnosis for head and neck paragangliomas can be broad if not suspected initially and encompasses primary clear cell or oncocytic lesions of thyroid, parathyroid, and salivary glands. Vascular metastases such as renal cell carcinoma or melanoma and even nested epithelioid sarcomas such as alveolar soft part sarcoma (historically miscategorized as ‘non-chromaffin paraganglioma’) could also be considered. The immunophenotype above also helps to resolve most of these considerations. Key immunohistochemical pitfalls include GATA3 reactivity in parathyroid lesions. However, parathyroid lesions are expected to express cytokeratins and tend to be more strongly positive for GATA3 than head and neck paragangliomas. Another key pitfall is the occasional presence of S100 positive sustentacular-like cells in neuroendocrine neoplasms/carcinomas. However, aside from the greater heterogeneity in growth patterns, neuroendocrine neoplasms/carcinomas are expected to express cytokeratins. Medullary thyroid carcinoma and hyalinizing trabecular tumor of thyroid can be delineated by TTF-1 and PAX-8 reactivity, in addition to expression of keratins and usually absent sustentacular cell populations. Hyalinizing trabecular tumor (historically known as paraganglioma-like adenoma of thyroid) is also known to harbor PAX8::GLIS3 or GLIS1 rearrangements.

The “rule of 10’s” as applied to head and neck paragangliomas essentially falls flat. Key deviations from this include malignant potential and hereditary disposition.

Head and neck paragangliomas have low metastatic potential (4-6%), though this varies by subsite. Vagal paragangliomas have the highest metastatic potential (~15%), and jugulotympanic paragangliomas having the lowest (2%). Histologic features such as increased mitotic activity, necrosis, spindling, loss of sustentacular staining, and lymphovascular invasion are not reliably predictive of metastatic potential.

In contrast, they have a strong hereditary disposition (40-85% in some series). Most have mutations involving the succinate dehydrogenase complex. In contrast to pheochromocytomas, the prevalence of VHL, RET, or NF1 mutations is low. As the majority of succinate dehydrogenase complex alterations affects the succinate dehydrogenase B subunit, loss of SDHB immunostaining can be used as a screening tool to inform subsequent genetic testing.

References

Hoang, V. T., et al. (2019). “Carotid body tumor: a case report and literature review.” J Radiol Case Rep 13(8): 19-30.
WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 9)
Williams, M. D. (2017). “Paragangliomas of the Head and Neck: An Overview from Diagnosis to Genetics.” Head Neck Pathol 11(3): 278-287.
Ordóñez NG, Ro JY, Mackay B. Alveolar soft part sarcoma. An ultrastructural and immunocytochemical investigation of its histogenesis. Cancer. 1989 May 1;63(9):1721-36. PMID: 2649226.

Quiz Answers

Q1 = B. These tumors are typically driven by mutations in the succinate dehydrogenase complex.

Q2 = False.

Contributors

Grayson Cole, DDS
PGY-3 Oral Pathology Resident
University of Pittsburgh School of Dental Medicine
University of Pittsburgh Medical Center

Raja R. Seethala, MD
Professor of Pathology and Otolaryngology
University of Pittsburgh Medical Center

Head & Neck Case Review 2022-08

2022-08-10

12:16 pm

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sinus

Head & Neck Case Review

August, 2022

History

A 36-year-old man presented with left eyelid drooping for one year along with progressively worsening headaches, blurry vision and diplopia for the prior month. A CT scan of the head showed a mass in the left maxillary sinus measuring 5.5 x 4.4 x 3.3 cm with bony destruction of the maxillary sinus walls and extension into the soft tissues of the posterior left orbit. The clinical and radiographic findings were highly suspicious for malignancy. A biopsy of the mass was subsequently performed. Representative CT scan radiographic images of the mass along with images of the surgical pathology are shown below.

Images

Quiz

1. To qualify as chronic invasive fungal rhinosinusitis (CIFR), symptoms must be present for at least:

A. 4 weeks
B. 8 weeks
C. 12 weeks
D. 26 weeks

2. Which of the following histopathologic features is seen in chronic granulomatous invasive fungal rhinosinusitis (CGIFR)?

A. Submucosal edema
B. Extensive fibrosis
C. Angioinvasive fungal hyphae
D. Well-formed granulomas with discrete rimming by mature lymphocytes
E. None of the above

Diagnosis

Chronic Granulomatous Invasive Fungal Rhinosinusitis

Chronic granulomatous invasive fungal rhinosinusitis (CGIFR) is an uncommon subtype of fungal rhinosinusitis (FR), which includes a wide range of pathologies from fungal infection of the paranasal sinuses. FR can first be broadly divided into either non-invasive or invasive subtypes based on the presence or absence of organism extension into the submucosa (and deeper tissues) by histopathology. Non-invasive FR includes fungus ball, saprophytic fungal infestation, and allergic FR. Invasive FR is less common than non-invasive FR and is divided into three major categories based on duration of symptoms and histopathologic features. These are 1) acute invasive FR (AIFR), 2) chronic invasive FR (CIFR), and 3) CGIFR. AIFR typically presents with a combination of congestion, rhinorrhea, headache, dizziness, fever and orbital swelling. Changes in vision and mentation, including diplopia, may also be present, as well as proptosis and tenderness to palpation of the facial sinuses. In the chronic forms of invasive FR, systemic symptoms tend to be absent, and patients typically present after an extended period of time with unilateral nasal obstruction or as a mass in the paranasal sinuses or nasal cavity. With longer delay in seeking medical care, visual and neurologic complications may develop.

AIFR consists of acute onset and aggressive progression of symptoms with a duration <30 days by definition. Symptoms are due to invasion of hyphae into the submucosal vasculature with resulting thrombosis, tissue infarction, and spread outside the sinuses into nearby bone and soft tissue. AIFR most commonly occurs in severely immunocompromised patients, in particular those with neutropenia resulting from hematologic malignancy, as well as patients with bone marrow or solid organ transplant, HIV, or those receiving systemic chemotherapy. Poorly controlled diabetes with diabetic ketoacidosis is also a well-known risk factor for AIFR. It is critical to diagnose AIFR swiftly as infection can progress rapidly, spread to the CNS and become fatal. The reported mortality rate is still approximately 50% but appears to be decreasing over time. Histopathologic findings include infarcted mucosa with minimal inflammatory reaction and vascular thrombosis with angioinvasive fungal hyphae. GMS and PAS special stains can help reveal vascular and soft-tissue invasion of fungus and better highlight the hyphal morphology. Cultures from AIFR most commonly grow Aspergillus sp. and Rhizopus sp. of the Zygomycetes order, with the former being more commonly isolated in the immunocompromised population and the latter being more commonly isolated in the diabetic population. Treatment consists of surgical debridement followed by intravenous antifungal therapy, as well as treating the individual’s underlying immunodeficiency, if possible.

The chronic forms of invasive FR, meanwhile, occur with slower, insidious symptom onset and progression with a duration of symptoms, by definition, of >12 weeks. They are more common in arid regions including India, Sudan, the Middle East, and northern Africa, and are rarely seen in the United States. Because they can present with a mass in the paranasal sinuses, it is not uncommon for these lesions to be mistaken for cancer on imaging. CIFR and CGIFR can both present in the setting of mild immunodeficiency, such as patients with diabetes or on steroid treatment, as well as in fully immunocompetent patients. Histopathologic findings from CIFR include extensive fibrosis and chronic inflammation without granulomas. Cultures from CIFR most commonly grow Aspergillus fumigatus. Histopathologic findings in CGIFR include submucosal fibrosis and non-caseating granulomatous inflammation. Fragmented fungal hyphae can be seen in the granulomatous areas by H&E, but the organisms can be much better seen on GMS or PAS special stains. Cultures in CGIFR most commonly grow Aspergillus flavus.Despite their prolonged duration of symptoms, both CIFRS and CGIFR also require prompt recognition and treatment with surgical debridement followed by systemic antifungal therapy.

In our case, the patient did not have any known underlying immunodeficiencies nor any risk factors that would contribute to immunosuppression, and clinical suspicion was highest for malignancy. H&E stains revealed sinonasal mucosa with extensive submucosal fibrosis and associated poorly formed granulomatous inflammation with multinucleated giant cells, mild chronic inflammation, scattered eosinophils, and foci of hyaline necrosis and dystrophic calcification. A GMS stain showed numerous scattered and fragmented fungal hyphae in the fibrous tissue. The hyphae were narrow and regular with obvious septation. Subsequent fungal cultures grew non-fumigatus Aspergillus species.

References

Akhondi, Hossein, et al. “Fungal Sinusitis.” StatPearls, 19 Jan. 2022, www-ncbi-nlm-nih-gov.proxy.library.vanderbilt.edu/books/NBK551496.
Alarifi, Ibrahim, et al. “Chronic Granulomatous Invasive Fungal Sinusitis: A Case Series and Literature Review.” Ear, Nose & Throat Journal, vol. 100, no. 5_suppl, 2020, pp. 720S-727S. Crossref, https://doi.org/10.1177/0145561320904620.
Craig, John R. “Updates in Management of Acute Invasive Fungal Rhinosinusitis.” Current Opinion in Otolaryngology & Head & Neck Surgery, vol. 27, no. 1, 2019, pp. 29–36. Crossref, https://doi.org/10.1097/moo.0000000000000507.
Deutsch, Peter George, et al. “Invasive and Non-Invasive Fungal Rhinosinusitis—A Review and Update of the Evidence.” Medicina, vol. 55, no. 7, 2019, p. 319. Crossref, https://doi.org/10.3390/medicina55070319.
Montone, Kathleen T., et al. “Fungal Rhinosinusitis: A Retrospective Microbiologic and Pathologic Review of 400 Patients at a Single University Medical Center.” International Journal of Otolaryngology, vol. 2012, 2012, pp. 1–9. Crossref, https://doi.org/10.1155/2012/684835.
Montone, Kathleen T. “Pathology of Fungal Rhinosinusitis: A Review.” Head and Neck Pathology, vol. 10, no. 1, 2016, pp. 40–46. Crossref, https://doi.org/10.1007/s12105-016-0690-0.
Montone, Kathleen T., and Virginia A. LiVolsi. “Inflammatory and Infectious Lesions of the Sinonasal Tract.” Surgical Pathology Clinics, vol. 10, no. 1, 2017, pp. 125–54. Crossref, https://doi.org/10.1016/j.path.2016.11.002.
Sharif, Muhammad Shahid, et al. “Frequency of Granulomatous Invasive Fungal Sinusitis in Patients with Clinical Suspicion of Chronic Fungal Rhinosinusitis.” Cureus, 2019. Crossref, https://doi.org/10.7759/cureus.4757.
Singh, Ajay Kumar. “Fungal Rhinosinusitis: Microbiological and Histopathological Perspective.” JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 2017. Crossref, https://doi.org/10.7860/jcdr/2017/25842.10167.

Quiz Answers

Q1 = C. The definition of chronic in chronic invasive (including granulomatous) fungal rhinosinusitis is symptom duration of > 12 weeks.

Q2 = B. Chronic invasive granulomatous fungal rhinosinusitis (CIGFR) shows extensive tissue fibrosis.

Contributors

George de Castro, BS, Medical Student
MD Program
Vanderbilt University School of Medicine

James Lewis Jr., MD
Department of Pathology, Microbiology, and Immunology
Vanderbilt University Medical Center

Head & Neck Case Review 2022-06

2022-06-10

12:29 pm

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oral cavity

Head & Neck Case Review

June, 2022

History

A 61-year-old female presented with a lesion on the right maxillary gingiva. Clinical examination revealed an ulcerated and endophytic lesion with associated leukoerythroplakia, involving the right maxillary gingiva and the adjacent soft tissue with noticeable bone loss. No lymphadenopathy was noted. An incisional biopsy was performed.

Images

Quiz

1. The histologic features are suggestive of:

A. Malignant melanoma
B. Squamous cell carcinoma
C. Traumatic ulcerative granuloma with stromal eosinophilia
D. Granulomatosis with polyangiitis
E. Langerhans cell histiocytosis

2. True or False: The prognostic role of eosinophilic infiltration in this disease is still unknown

True
False

Diagnosis

Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is always an important entity to consider in the differential diagnosis of any unexplained lesion in the oral cavity. SCC is the most common malignancy of the oral cavity. It typically exhibits a peak incidence in the elderly with an established relationship with tobacco and/or alcohol abuse. About 50,000 cases of oral and oropharyngeal SCC are diagnosed annually and approximately 11,000 people die of this disease each year in the US.

Oral SCC is usually slow-growing and has a varied clinical presentation, often appears as leukoplakic and/or erythroplakic lesions especially in the early course of the disease or as a fungating ulcerated mass. Greater than 50% of intraoral cancers occur on the tongue, with 2/3 of these presenting on the posterior lateral border and another 20% on the anterior lateral or ventral surfaces. The floor of the mouth is the next most common location accounting for about 1/3 of the cases. Other involved sites are soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate in descending order of frequency. Therefore, SCC arising from the gingiva or alveolar ridge is a bit unusual. These SCCs occur most frequently on the attached gingiva and keratinized edentulous tissues in the posterior regions of the mandible. Most importantly gingival SCC often clinically mimics gingivitis or periodontal disease. Loosening of the involved teeth which necessitate extraction, is a frequent clinical scenario. Eventually, the socket fails to heal, and hyperplastic tissues would be noted.

The most intriguing feature of this case is the histological findings of malignant neoplastic cells arranged in an almost theques-like pattern seen in melanoma. The neoplastic cells lack dyskeratosis. The invasive process elicits an inflammatory cell response, but marked eosinophilia is noted. Immunohistochemistry stains for melanoma were negative, however, AE1/3 and p40 were positive within lesional cells.

Lowe and Fletcher were the first to study the role of tissue eosinophilia in oral SCC in 1984. Falconieri (2008) suggested the eosinophilic-rich squamous cell carcinoma as a possible new microscopic entity of SCC. Several studies suggest an association between tissue eosinophilia and invasive SCC, which could be a reliable indicator of invasive tumors in small biopsies of superficial lesions. Another study showed that the presence of tissue eosinophilia particularly in close association with striated damaged muscle fibers is associated with advanced disease. Some studies suggested that tissue eosinophilia could be used as a predictive factor for lymph node metastases or locoregional recurrences. However, no significant association between tissue eosinophilia and survival outcomes was reported.

The biological role of tissue eosinophilia in SCC is still unclear and further studies are needed to clarify the prognostic role of eosinophilic infiltration in SCC.

Unfortunately, gingival SCCs are notorious for this endophytic growth pattern and are often discovered very late in the course of the disease when they explode onto the surface. The prognosis is very poor despite advances in treatment with the overall 5-year survival rate being about 50%. The mainstay of treatment is surgery with or without radiotherapy. However, there is significant morbidity from the surgery and radiation therapy as well. Early detection is critical to improve the outcome for these patients.

References

Mascitti M, Togni L, Rubini C, Troiano G, Lo Muzio L, Santarelli A. Tumour-associated tissue eosinophilia (TATE) in oral squamous cell carcinoma: a comprehensive review. Histol Histopathol. 2021;36(2):113-122. doi:10.14670/HH-18-250
Lowe D, Fletcher CD. Eosinophilia in squamous cell carcinoma of the oral cavity, external genitalia and anus–clinical correlations. Histopathology. 1984;8(4):627-632. doi:10.1111/j.1365-2559.1984.tb02375.x
Falconieri G, Luna MA, Pizzolitto S, DeMaglio G, Angione V, Rocco M. Eosinophil-rich squamous carcinoma of the oral cavity: a study of 13 cases and delineation of a possible new microscopic entity. Ann Diagn Pathol. 2008;12(5):322-327. doi:10.1016/j.anndiagpath.2008.02.008
Oliveira DT, Biassi TP, Faustino SE, Carvalho AL, Landman G, Kowalski LP. Eosinophils may predict occult lymph node metastasis in early oral cancer. Clin Oral Investig. 2012;16(6):1523-1528. doi:10.1007/s00784-011-0651-7
Rakesh N, Devi Y, Majumdar K, Reddy SS, Agarwal K. Tumour associated tissue eosinophilia as a predictor of locoregional recurrence in oral squamous cell carcinoma. J Clin Exp Dent. 2015;7(1):e1-e6. Published 2015 Feb 1. doi:10.4317/jced.51610

Quiz Answers

Q1 = B. Squamous Cell Carcinoma

Q2 = True

Contributor

Saja Alramadhan, BDS, OMFP
Fellow, Department of Oral and Maxillofacial Pathology
University of Florida College of Dentistry

Head & Neck Case Review 2021-12

2021-12-05

3:10 pm

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maxillary sinus

Head & Neck Case Review

December, 2021

History

An elderly man presented with a maxillary sinus mass. Physical exam showed softness of the right hard palate and a nasal endoscopy showed a mass extending into the right maxillary sinus. A CT and MRI showed a mass within the right maxillary sinus with bowing of the medial maxillary wall and cortical breakthrough of the posterior wall. The mass demonstrated extension into the fat of the right masticator space and involvement of the right maxilla. A biopsy of the mass was performed. Representative imaging of the mass along with H&E stained sections and immunohistochemical stains of the biopsy are shown.

Images

Quiz

Which of the following best characterizes the process shown?

A. Clusters of benign remnant epithelial cell rests
B. A reactive inflammatory process disrupting normal epithelial elements
C. A malignant epithelial process
D. A malignant process derived from embryologic remnants

2. What is the immunohistochemical stain shown in the last image?

A. p63
B. Brachyury
C. SOX-10
D. WT1

Diagnosis

Metastatic Chordoma

Chordoma is a rare, low to intermediate-grade malignant neoplasm of bone that is derived from and phenotypically resemble embryonic notochord remnants. During embryonic development, the notochord serves as a primitive axial skeleton from the third/fourth week of gestation until the seventh week of gestation. Incomplete regression of notochord tissue along this notochord tract is thought to give rise to chordomas of the axial skeleton with the most common sites being sacrococcygeal region, craniocervical/base of skull, and vertebral column. Benign notochord cell tumors share a similar midline pattern of distribution and similar morphologic features with chordomas, suggesting that they may represent a precursor to chordomas, however, this remains controversial. Clinically, chordomas are typically identified within the 4^th-8^th decades of life.

Histologically, chordomas are classified into three types; conventional chordomas, chondroid chordomas, and dedifferentiated chordomas. Conventional chordomas are generally characterized by cords and strands of intermediate to large epithelioid cells with abundant cytoplasm and large hyperchromatic nuclei. However, they can also be composed of smaller, more stellate cells with minimal cytoplasm. The identification of scattered so-called ‘physaliphorous’ cells, characterized by abundant mucin-filled vacuolated cytoplasm (giving them a “bubbly” appearance), are a useful diagnostic feature. Abundant myxoid stroma and a lobulated growth pattern separated by fibrous septae are frequently seen. Chondroid chordomas (~5% of chordomas) are characterized by areas of immature chondroid matrix while dedifferentiated chordomas (~5% of chordomas) are characterized by atypical spindle cells/high-grade sarcomatous elements. Chordomas are typically positive for pancytokeratin, EMA, S100, and brachyury (highly sensitive and specific). Additionally, mucicarmine and/or PAS can be used to highlight intracellular mucin.

The metastatic chordoma presented in this case was positive for pancytokeratin, EMA, S100, and brachyury. The tumor was composed of cords, nests, and single atypical epithelioid cells in a highly reactive background. Characteristic physaliphorous cells were not identified by either H&E or mucicarmine. Given the initial non-specific findings, the patient’s clinical history including the concerning radiologic features, was invaluable in working up this case. Review of the patient’s medical history revealed that he had a remote history of sacral chordoma with pelvic metastases approximately 20 years ago. Until his recent presentation, his disease process was notable for multiple pulmonary masses/nodules, relatively stable bony disease, and what was presumed to be a stable right maxillary sinus mucus retention cyst.

Chordomas are characterized by a high regional recurrence rate of over 50% following treatment with surgical resection ± radiotherapy. Additionally, late recurrences greater than 10 years are relatively common, necessitating long term follow-up. The rate of metastasis has been estimated at around 15-20%, with the most common sites being lung, liver, bone, skin, and lymph nodes. However, a number of rare secondary sites of metastasis have been reported in the literature; including heart, breast, tongue, mandible, genitalia, fingertips, and orbit. Without appropriate clinical history these lesions can present a diagnostic challenge.

References

Young VA, Curtis KM, Temple HT, Eismont FJ, DeLaney TF, Hornicek FJ. Characteristics and Patterns of Metastatic Disease from Chordoma. Sarcoma. 2015;2015:517657.

Rohatgi S, Ramaiya NH, Jagannathan JP, Howard SA, Shinagare AB, Krajewski KM. Metastatic Chordoma: Report of the Two Cases and Review of the Literature. Eurasian J Med. 2015;47(2):151-154.

McPherson CM, Suki D, McCutcheon IE, Gokaslan ZL, Rhines LD, Mendel E. Metastatic disease from spinal chordoma: a 10-year experience. J Neurosurg Spine. 2006 Oct;5(4):277-80.

Wasserman JK, Gravel D, Purgina B. Chordoma of the Head and Neck: A Review. Head and Neck Pathology. 2018 Jun;12(2):261-268.

Karpathiou G, Dumollard JM, Dridi M, Dal Col P, Barral FG, Boutonnat J, Peoc’h M. Chordomas: A review with emphasis on their pathophysiology, pathology, molecular biology, and genetics. Pathol Res Pract. 2020 Sep;216(9):153089. doi: 10.1016/j.prp.2020.153089. Epub 2020 Jun 29. PMID: 32825957.

Quiz Answers

Q1 = D. A malignant process derived from embryologic remnants

Q2 = B. Brachyury

Contributor

Troy Hutchens, MD, PhD
Head & Neck Surgical Pathology Fellow
Department of Pathology & Immunology
Washington University School of Medicine

Head & Neck Case Review 2021-10

2021-10-13

3:39 pm

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mucosal, oropharynx

Head & Neck Case Review

October, 2021

History

An adult woman with a significant smoking history presented to the emergency department with chronic unilateral otalgia and worsening odynophagia causing decreased appetite and weight loss. The patient denied fevers or B symptoms. Physical exam demonstrated a firm, exophytic, non-ulcerated mass in the palatine tonsil. CT scan showed a tonsillar mass with bilateral lymphadenopathy throughout the neck. The patient underwent bilateral tonsillectomy.

Images

Quiz

Q1. What is the diagnosis?

A. Extramedullary plasmacytoma
B. Systemic lupus erythematosus
C. T. pallidum infection
D. Granulomatosis with polyangiitis

Q2. What is the most specific confirmatory test?

A. c-ANCA
B. Flow cytometry, serum protein electrophoresis and bone marrow biopsy
C. Direct immunofluorescence
D. Serum RPR and VDRL
E. Serum RPR and FTA-ABS

Diagnosis

Oropharyngeal syphilis

Syphilis is a sexually transmitted infection caused by the bacteria Treponema pallidum. In general, the histologic features of syphilis are dense chronic inflammatory infiltrates composed mostly by lymphocytes and plasma cells with vague perivascular accentuation. Syphilitic oral ulcers with only acute inflammation devoid of lymphoplasmacytic infiltrate have been reported. Other findings may include effacement of the normal architecture of the involved organ, swollen endothelial cells, and occlusive endovasculitis (luetic vasculitis). Lymph nodes may show a marked follicular hyperplasia, thickened capsule, fibrosis, necrosis, and/or multinucleated giant cells. The morphologic differential diagnosis is broad and includes other infections (bacterial, fungal and viral), trauma, neoplasms, auto-immune disorders, and allergies. In lymph nodes, the morphologic differential diagnosis includes reactive hyperplasia, granulomatous diseases such as tuberculosis, sarcoidosis, cat scratch disease, and even follicular lymphoma because of marked reactive follicular hyperplasia.

Reports of involvement of oral cavity and oropharynx are rare in the pathology literature. A recent case series by Deng et al (1) described three cases of oral cavity involvement, one of which also showed oropharyngeal involvement. Most chancres occur in the anogenital region, but the oral cavity and lips are not uncommon extragenital sites. In the oral cavity, primary syphilis usually presents in the form of a painless non-healing ulcer. The classic presentation for secondary syphilis in the oral cavity consist of multiple white mucous patches, with condyloma lata and split papules also reported.

Hamlyn et al (5) reported 3 cases of secondary syphilis presenting as tonsillitis in Australia in 2006, one of which had a tonsillectomy showing reactive follicular hyperplasia with increased plasma cells. In the present case, there was complete effacement of tonsil architecture without recognizable crypts in both tonsils with pseudotumor in one tonsil. Vascular accentuation of the infiltrates and edematous endothelial cells were important morphologic clues to the diagnosis. Because the tonsils are specialized mucosa, morphologic features may include those described in lymph nodes.

The presence of the spirochete can be demonstrated by immunohistochemistry which will highlight corkscrew shaped organisms and may show perivascular aggregates of the organisms, as in this case. Most laboratories use an antibody that is highly specific for T. pallidum, but confirmation with serology is generally recommended (discussed below). Special staining with Warthin-Starry stain is a less specific alternative when immunohistochemistry is not available.

Transmission occurs person to person by direct contact with a chancre. Despite well-documented prevention methods and treatment, the incidence rates has been steadily increasing throughout the United States since the year 2000, with a steady increase involving many population groups. Untreated syphilis is potentially life-threatening with consequences that include neurological complications, hearing loss, and blindness.

Based on the duration of the infection, syphilis can be classified as primary, secondary, tertiary, and latent. Primary syphilis typically presents as a painless ulceration at the site of inoculation, usually solitary, and associated to localized lymphadenopathy that develops within 3 weeks of the exposure. Secondary syphilis usually occurs within 2 to 8 weeks from exposure and is characterized by skin rashes and mucous lesions, however the presentation can be even more nonspecific with symptoms such as, fever, pain and disseminated lymphadenopathy. The tertiary stage occurs within 10 to 30 years of the infection, and symptoms vary according the affected organs (any organ can be affected).

T. pallidum cannot be cultured in the clinical microbiology laboratory, therefore serologic tests are generally necessary for the diagnosis of the disease in any stage. A reactive treponemal test (FTA-ABS) in addition to a reactive nontreponemal test (RPR) is highly specific for infection. Treponemal tests may remain reactive indefinitely, and are not useful for monitoring therapy. Nontreponemal tests include RPR and VDRL. These tests detect IgM and IgG anti-cardiolipin antibody, produced in response to host cell damage and cardiolipins released from treponemes, which can lead to false positive tests in the presence of other anti-cardiolipin antibody producing conditions. In addition, RPR titers are negative or low early in primary syphilis, can become negative after several years, even without therapy and titers drop rapidly after treatment of primary or secondary syphilis. All positive nontreponemal tests must be confirmed by a treponemal test to detect antibodies against the T. pallidum, such as FTA-ABS, that remains reactive, irrespective of treatment, for increased specificity.

To date, the treatment of choice is still penicillin as no resistance of the Treponema pallidum has been observed against this antibiotic. The dosage varies according the stage of the disease. In the United States syphilis is listed in the National Notifiable Diseases Surveillance System (NNDSS) of the Centers for Disease Control, and all cases of probable and confirmed syphilis meeting the CDC case definitions should be reported.

The clinical diagnosis of syphilis can be challenging because of the many different presentations. Similarly, the histopathology of syphilis is characterized by nonspecific features that can mimic other disorders. As a consequence, a high index of suspicion is required for the diagnosis. Multi-institutional collaboration studies may be useful to describe specific histopathologic characteristics of primary or secondary syphilis occurring in specialized mucosae of the oropharynx.

References

Deng F, Thompson LDR, Lai J. Unexpected Reason for Non-healing Oral Ulcers: Syphilis. Head Neck Pathol. 2021 Aug 3. doi: 10.1007/s12105-021-01348-y. Epub ahead of print. PMID: 34342809.
Thompson LDR. Oral Syphilis. Ear Nose Throat J. 2021 Sep;100(5_suppl):538S-539S. doi: 10.1177/0145561319890154. Epub 2019 Nov 24. PMID: 31760793.
Schmidt R, Carson PJ, Jansen RJ. Resurgence of Syphilis in the United States: An Assessment of Contributing Factors. Infect Dis (Auckl). 2019;12:1178633719883282. Published 2019 Oct 16. doi:10.1177/1178633719883282
Komeno Y, Ota Y, Koibuchi T, Imai Y, Iihara K, Ryu T. Secondary Syphilis with Tonsillar and Cervical Lymphadenopathy and a Pulmonary Lesion Mimicking Malignant Lymphoma. Am J Case Rep. 2018 Mar 4;19:238-243. doi: 10.12659/ajcr.907127. PMID: 29502129; PMCID: PMC5846205.
Hamlyn E, Marriott D, Gallagher RM. Secondary syphilis presenting as tonsillitis in three patients. J Laryngol Otol. 2006 Jul;120(7):602-4. doi: 10.1017/S002221510600096X. Epub 2006 Mar 24. PMID: 16556350.
Yuan Y, Zhang X, Xu N, et al. Clinical and pathologic diagnosis and different diagnosis of syphilis cervical lymphadenitis. Int J Clin Exp Pathol. 2015;8(10):13635-13638. Published 2015 Oct 1.
ClinLab Navigator [http://www.clinlabnavigator.com/syphilis-serology.html]. Accessed September 2021

Quiz Answers

Q1 = C. T. pallidum infection

Q2 = E. Serum RPR and FTA-ABS

Contributors

Igor Damasceno Vidal, MD, PGY-2 resident
Pathology Residency Program
University of Alabama at Birmingham School of Medicine

Manuel Lora Gonzalez, MD, Assistant Professor
Department of Pathology
University of Alabama at Birmingham Hospital & School of Medicine

Head & Neck Case Review 2021-07

2021-07-20

1:31 pm

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mucosal

Head & Neck Case Review

July, 2021

History

A 50-year-old man presents with a 6-month history of a left tongue lesion which was biopsied. Characteristic H&E stained sections and one immunostain are shown.

Images

Quiz

Q1. Which of the following is true regarding this lesion?

A. It is the result of a proliferation of histiocytes.
B. The lesional cells are filled with PAS+, diastase resistant granules.
C. The overlying mucosal process is characteristic of basal cell carcinoma.
D. Leukoplakia and erythroplakia are precursors of this lesion.

Q2. Which immunohistochemical stain is used to help diagnose this lesion and is shown here?

A. CK5/6
B. SOX10
C. S100
D. Desmin

Diagnosis

Granular cell tumor with pseudoepitheliomatous hyperplasia

Granular cell tumor (GCT) is a relatively uncommon lesion of Schwann cell differentiation which can affect any anatomic location. The most frequently-affected region is the head and neck, with the highest prevalence in the tongue. It typically arises in the third to the sixth decades and has a slight female preponderance.

A properly oriented H&E–stained section is very important for diagnostic interpretation. Histologically, GCT is characterized by an ill-defined tumor, composed of plump polygonal cells with small nuclei and abundant eosinophilic granular cytoplasm. Pseudoepitheliomatous hyperplasia (PEH) occurs in up to 50% of granular cell tumors – typically in the overlying epithelium – and often mimics invasive squamous cell carcinoma (SCC), although there have been rare reports of the coexistence of PEH and invasive SCC. The exact explanation for the association between GCT and PEH is unknown but is postulated to be due to the proliferative activity of basal cells that interact with granular cells and neighboring epithelial cells.

PEH is a reactive epithelial proliferation found in association with several neoplastic and reactive processes. Histologically, it is seen as cords and strands of squamous epithelium that extends to the underlying dermis or submucosa and that displays a pseudo-infiltrative pattern of growth which can closely mimic invasive squamous cell carcinoma. PEH can rarely be found in association with basal cell carcinoma (BCC) but the epidermal hyperplasia has a follicular differentiation and is often eccentric relative to the BCC rather than directly overlying it. Differentiating PEH from invasive SCC especially on superficial and limited biopsies can be extremely challenging. SCC is favored by more pronounced cytologic atypia and other features of malignancy such as nuclear pleomorphism, increased mitotic activity (especially presence of atypical mitoses), and perineural/lymphovascular invasion. When classic cytologic signs of malignancy are lacking, PEH clinical findings and/or the presence of an underlying reason for the presence of PEH tilt the diagnostic probability in favor of PEH.

By immunohistochemistry, the tumor cells are positive for S100 (cytoplasmic and nuclear staining as shown in the image), SOX10 (nuclear), inhibin, and calretinin. The cytoplasmic eosinophilic granules (phagolysosomes) are PAS positive, diastase resistant, and are also often highlighted by CD68.

GCT is usually a benign tumor. Histologic criteria for malignant GCT is still a topic of debate. GCTs with nuclear pleomorphism, high N:C ratio, prominent nucleoli, spindle cell morphology, necrosis, and increased mitotic activity >2/10 are considered malignant. The optimal treatment for GCT is complete surgical excision as they are not sensitive to radiotherapy or chemotherapy.

References

Mobarki M, Dumollard JM, Dal Col P, Camy F, Peoc’h M, Karpathiou G. Granular cell tumor a study of 42 cases and systemic review of the literature. Pathol Res Pract. 2020 Apr;216(4):152865. doi: 10.1016/j.prp.2020.152865. Epub 2020 Feb 12. PMID: 32089415.
Caroppo, Danila, et al. “Coexistent Squamous Cell Carcinoma and Granular Cell Tumor of Head and Neck Region: Report of Two Very Rare Cases and Review of the Literature.” International Journal of Surgical Pathology, vol. 26, no. 1, 7 Aug. 2017, pp. 47–51.
Elena Zarovnaya and Candice Black. Distinguishing Pseudoepitheliomatous Hyperplasia from Squamous Cell Carcinoma in Mucosal Biopsy Specimens from the Head and Neck. Archives of Pathology & Laboratory Medicine: August 2005, Vol. 129, No. 8, pp. 1032-1036.
Nayak, Vaidhehi Narayan, et al. “Pseudoepitheliomatous Hyperplasia in Oral Lesions: A Review.” Journal of International Oral Health: JIOH, vol. 7, no. 9, 2015, pp. 148–52.

Quiz Answers

Q1 = B. The lesional cells are filled with PAS+, diastase resistant granules

Q2 = C. S100

Contributor

Qiuying Shi, MD, MS (Assistant Professor, Lead author)
Oluwaseun Ogunbona, MD, PhD (PGY3 resident)
Department of Pathology
Emory University Hospital Midtown
Emory University School of Medicine, Atlanta, GA

Head & Neck Case Review 2021-06

2021-06-10

9:08 am

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mandible, mesenchymal

Head & Neck Case Review

June, 2021

History

A 44-year-old woman presented with a 2-month history of right mandibular pain and mild swelling. Recent developments included paresthesia along the lip and right side of the chin. A cone beam CT study showed irregular resorption of bone including erosion of the buccal cortex. Representative axial and coronal slices of the mass along with the H&E stained sections and immunostains of the biopsied tissue are shown.

Images

Quiz

Q1. What is the characteristic genetic event in this tumor in children?

A. PAX 3/7-FOX01 gene fusion
B. FGFR4, RAS, AKT pathway mutations
C. PTEN hypermethylation
D. NCOR2 or VGLL2 gene fusion

Q2. Which one of the following is a morphologic variant of this tumor?

A. Sclerosing
B. Embryonal
C. Pleomorphic
D. Alveolar

Diagnosis

Spindle cell rhabdomyosarcoma of the mandible

Spindle cell/sclerosing rhabdomyosarcomas are a rare subtype of rhabdomyosarcomas accounting for 3–10% of rhabdomyosarcomas, affecting adults and children. In adults, the deep soft tissue of the head and neck region is most commonly involved, accounting for over 50% of the cases. In children, the paratesticular region is the most common site followed by the head and neck. Tumors in adults and children are more common in males with a male to female ratio of 6:1.

Spindle cell rhabdomyosarcomas show an infiltrative cellular proliferation of spindle-shaped tumor cells having elongated hyperchromatic nuclei and pale eosinophilic cytoplasm arranged in intersecting fascicular or herringbone patterns. A storiform pattern may also be seen, focally. Scattered rhabdomyoblasts with eccentrically placed nuclei may also be seen. Sclerosing rhabdomyosarcomas are characterized by prominent hyalinization or sclerosis with tumor cells arranged in cord, nests, trabecular, or microalveolar patterns. Tumors expressing a sclerosing morphology are more common in the limbs. Immunohistochemically, the tumor cells are positive for desmin, myogenin, and MyoD1. Some tumors show only very limited immunoreactivity for desmin and myogenin but are often strongly positive for MyoD1.

Infantile/childhood spindle cell/sclerosing rhabdomyosarcomas show a NCOR2– or VGLL2-related gene fusion. MYOD1 (L122R)-mutant subset is more common among adults and is associated with an aggressive clinical outcome. The MYOD1-mutant subset occasionally shows a PIK3CA mutation. A third subset of tumors lack recurrent genetic abnormalities. Rare intraosseous spindle cell rhabdomyosarcomas harbor a gene fusion of EWSR1/FUSTFCP2 and MEIS1-NCOA2.

Adult tumors are clinically aggressive. Recurrence and metastasis are reported in 50% of cases with metastasis to lymph nodes and lungs being common. Radiotherapy & function-preserving surgery are mainstay of treatment for resectable sarcomas. Intensive multi-agent therapy is used in patients with high-risk rhabdomyosarcomas. These include dose-compressed cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide and radiation. However, the prognosis is poor.

In contrast to the adult tumors, childhood tumors demonstrate a low stage at presentation. The prognosis is good in patients under 10 years of age with over 95% survival at 5 years.

References

Chiles MC, Parham DM, Qualman SJ, Teot LA, Bridge JA, Ullrich F, Barr FG, Meyer WH; Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Sclerosing rhabdomyosarcomas in children and adolescents: a clinicopathologic review of 13 cases from the Intergroup Rhabdomyosarcoma Study Group and Children’s Oncology Group. Pediatr Dev Pathol. 2004;7:583–94.
Nascimento AF, Fletcher CD. Spindle cell rhabdomyosarcoma in adults. Am J Surg Pathol. 2005;29:1106–13.
Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, Zin A, Agaram NP, LaQuaglia MP, Wexler LH, Antonescu CR. A Molecular Study of Pediatric Spindle and Sclerosing rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases. Am J Surg Pathol. 2016;40(2):224–35.
Rekhi B, Upadhyay P, Ramteke MP, Dutt A. MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol. 2016;29(12):1532–40.
Nascimento AF, Barr FG. Spindle cell/Sclerosing rhabdomyosarcoma. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. In: WHO classification of tumours of soft tissue and bone. Lyon, IARC Press, 2013:134–5.
Agaram NP, LaQuaglia MP, Alaggio R, Zhang L, Fujisawa Y, Ladanyi M, Wexler LH, Antonescu CR. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019;32:27–36.

Quiz Answers

Q1 = D. NCOR2 or VGLL2 gene fusion

Q2 = A. Sclerosing

Contributor

Yeshwant B. Rawal, BDS, MDS, MS
Professor, Department of Surgical Sciences
Marquette University School of Dentistry, Milwaukee, WI

Head & Neck Case Review 2021-04

2021-04-06

8:02 am

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mesenchymal, oral cavity

Head & Neck Case Review

April, 2021

History

A 68-year-old African American male presented with a nontender mass under his tongue for 2 weeks. He had dysarthria because of compromised tongue movement. He denied pain, bleeding, dysphagia, loss of appetite, weight changes, and shortness of breath. There was no history of prior swelling, trauma, or oral cavity surgeries. Clinical examination revealed a mobile, solid, non-tender, oval-shaped right sublingual mass (3.0 x 2.0 cm). No notable cervical adenopathy was found.

CT scan showed a well-circumscribed, oblong shaped hyperdense mass (4.1 x 2.5 x 4.0 cm) situated within the floor of mouth/right sublingual gland with mild mass effect upon the midline intrinsic tongue musculature. No calcification or sialolith were identified. There was no surrounding inflammation or cervical lymphadenopathy. Excision of the mass was performed.

Images

Quiz

Q1. Which genetic alteration is associated with this tumor?

A. SS18-SSX1/SSX2/SSX4 fusion
B. EWSR1-FLI1 fusion
C. NAB2-STAT6 fusion
D. PLAG1 rearrangement

Q2. Histologic features of the tumor always predict outcome in these patients.

A. True
B. False

Diagnosis

Solitary Fibrous Tumor (SFT)

Solitary fibrous tumor (SFT) is a rare soft tissue tumor of mesenchymal phenotype. Originally described in the pleura by Klemperer and Rabin in 1931, these tumors have represented a unique diagnostic and treatment challenge. SFT may be found in almost any site of the body with the intrathoracic location being the most common. Other locations include the trunk, extremities, head and neck, and intracranial. Those in the head and neck may arise in the sinonasal tract, oral cavity, larynx, or orbit. In the oral cavity, buccal mucosa is the most common location. Less than 10 cases have been reported in the floor of mouth.

Grossly, SFTs tend to be well circumscribed and have a smooth exterior with a lobulated cut surface. Histologically, they are composed of spindle cells and show variation of growth patterns, including fascicular, storiform, or herringbone. Nuclei can be wavy and neural-like or blunt and ovoid. Frequently, there are both hypercellular areas as well as hypocellular areas with stromal sclerosis. Rope-like, linear stromal sclerosis is highly characteristic of this tumor. Spindled cells are separated by endothelial-lined, dilated, angulated, branching vascular spaces, often referred to as “hemangiopericytoma or HPC-like”, after the vessels identified in intracranial hemangiopericytomas (most of which are now known to share similar morphology and identical genetics to SFTs of other sites). The vessels range in size from capillaries to large and patulous but usually do not have muscular walls. There is no cytologic atypia within the endothelial cells. Additionally, nuclear pleomorphism is absent or limited in the spindle cells. Chromatin is usually open with inconspicuous nucleoli. Mitotic activity is usually rare. A subset of SFTs may have atypical histological features such as areas of hypercellularity, infiltrative borders, moderate to marked nuclear pleomorphism, necrosis, or >4 mitoses per 10 HPF, and are more likely to behave in a malignant fashion. While the spindle cells are positive for CD34, Bcl-2, CD99, and vimentin, nuclear expression of STAT6 is most specific – as it reflects the underlying NAB2-STAT6 gene fusion. This fusion is present in SFTs of all anatomic sites.

In most cases, complete surgical removal is curative. However, prediction of behavior based on histological criteria alone may not be accurate as SFTs may recur or metastasize even in the absence of atypical histological features. Therefore, long-term follow-up is recommended for all SFTs.

References

Gold JS, Antonescu CR, Hajdu C, et al. Clinicopathologic correlates of solitary fibrous tumors. Cancer 2002;94:1057–68
Fan CY, Van Hemert RL, Thomas JR, et al. Atypical solitary fibrous tumor of the larynx. Otolaryngol Head Neck Surg 2006;134:880–2
Hasegawa T, Matsuno Y, Shimoda T, et al. Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior. Hum Pathol 1999;30:1464–73.
Rodrigues, Fernandes, et al. Solitary fibrous tumor of the floor of the mouth. J Clin Exp Dent. 2017 Sep; 9(9): e1153–e1157.

Quiz Answers

Q1 = C. NAB2-STAT6 fusion

Q2 = B. False

Contributors

Shajia Ansari, MD
Resident
Pathology and Immunology
Baylor College of Medicine
Houston, TX US

Syeling Lai, MD
Associate Professor
Pathology and Immunology
Baylor College of Medicine
Houston, TX US

Head & Neck Case Review 2021-02

2021-02-11

3:43 pm

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parathyroid

Head & Neck Case Review

February, 2021

History

A 65 year-old male with no significant past medical history presents with fatigue, difficulty swallowing, and voice changes for several months duration. CT scan showed an 8 cm left-sided neck mass. The patient underwent left hemithyroidectomy and parathyroidectomy. CT imaging, H&E sections, and immunostains of the mass are shown.

Images

Quiz

Q1. All of the following are characteristic features of this tumor, EXCEPT:

A. Invasive growth involving adjacent structures
B. Vascular and/or perineural invasion
C. Nodular growth pattern with broad bands of fibrous connective tissue
D. Rare recurrence after resection

Q2. CDC73 mutation is the molecular driver in the pathogenesis of this tumor.

A. True
B. False

Diagnosis