Category: H&amp;N Case Review

2024-04-04

3:39 pm

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salivary

Head & Neck Case Review

April, 2024

History

A 60-year-old man presents with a slowly growing painless lesion confined to the parotid gland. Superficial parotidectomy reveals a 2.0 cm cystic mass. Histologically, this mass is a well-delineated nodule without necrosis or increased mitotic activity. The stroma is fibrotic with mild chronic inflammation but lacks a prominent lymphoid component.

Images

Quiz

1. True or False: This benign salivary gland tumor occurs exclusively in the parotid gland.

2. True or False: This salivary gland tumor is associated with germline mutations in mismatch repair genes.

Contributors

Melad N. Dababneh, MBBS
Head and Neck Pathology Fellow
Cleveland Clinic

Christpher C. Griffith, MD, PhD
Associate Professor of Pathology
Cleveland Clinic Lerner College of Medicine

Head & Neck Case Review 2024-03

2024-03-06

3:32 pm

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mandible, mesenchymal

Head & Neck Case Review

March, 2024

History

A 12-year-old female presented with jaw pain and a firm mass involving the mandible. Imaging revealed an expansile lesion centered around the mandibular ramus with uniform and sclerotic density, root resorption, and prominence of involved periodontal ligament spaces. The patient underwent a hemi-mandibulectomy, which revealed a poorly demarcated tan mass surrounding and causing root resorption of the molar teeth. Histologic examination was performed.

Images

Quiz

1. Which of the following is a common molecular finding associated with this neoplasm?

A. SATB2 rearrangement
B. MDM2 amplification
C. GNAS mutation
D. USP6 rearrangement

2. True or False: The mandible is the most common site for this neoplasm.

Contributors

Melad N. Dababneh, MBBS
head and neck pathology fellow, Cleveland Clinic

Ivan J. Stojanov, DMD
staff pathologist, Cleveland Clinic

Head & Neck Case Review 2023-12

2023-12-04

3:00 pm

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oropharynx

Head & Neck Case Review

December, 2023

History

A 64-year-old male presents with a left sided neck mass that he had noticed one month ago. On ultrasonographic examination, the mass was 4.3 x 3.3 x 2.2 cm with heterogeneous appearance. An ultrasound guided needle biopsy was performed and displayed malignant cells compatible with metastatic squamous cell carcinoma. A p16 immunostain was strongly positive, high risk human papillomavirus (HPV) E6/E7 mRNA in-situ hybridization was equivocal. A follow up ¹⁸F-fluorodeoxyglucose (FDG) PET/CT showed uptake in the left cervical level II lymph node, and symmetric mild uptake in bilateral palatine tonsils. A transoral robotic tonsillectomy and base of tongue resection was performed to localize the site of primary. A firm fibrotic area was noted in the left tonsil on palpation and cut surface. A representative frozen section was taken:

Images

Quiz

1. Which of the following is most likely representative of the finding on frozen section?

A. Hamartoma
B. Teratoma
C. Choristoma
D. Pleomorphic adenoma

2. What is the most common cartilage producing parapharyngeal space tumor?

A. Pleomorphic adenoma
B. Teratoma
C. Chondroma
D. Chondrosarcoma

Diagnosis

Cartilaginous choristoma

Cartilaginous choristomas, described as early as 1890 by Berry in tongue, are uncommon deep-seated proliferations of normal appearing cartilage. These often have significant fibrosis as seen here, prompting the alternative classification as chondroid metaplasia. Etiologically, this is likely incorrect as the cartilage typically appears mature with a well-formed perichondrium and without dystrophic calcification. In tonsil, despite the proximity to lymphoid stroma, cartilaginous choristomas are not particularly inflamed. The prevalence of cartilaginous choristoma in the tonsil is likely underreported since non-neoplastic tonsils are only representatively submitted for histologic evaluation but one prospective study indicates a prevalence of ectopic cartilage in tonsil specimens being as high as 6%. The incidental occurrence on intraoperative examination represents a modern phenomenon that can attributed to the advent of transoral robotic surgery (TORS) for the diagnosis and treatment of oropharyngeal squamous cell carcinoma. This case may also very well be the only gross photo documentation of a cartilaginous choristoma, albeit on a frozen section block.

The terms choristoma and hamartoma are often grouped together as developmental anomalies, however strictly speaking, choristomas are benign growths consisting of normal tissue in locations where the tissue is not normally found (ectopic). In comparison, hamartomas are benign growths of mature cells in their normal location, but in a disorganized manner. Neoplasms may occasionally enter the differential diagnosis for cartilaginous choristoma but are usually much larger and are distinguished by the presence of other elements. The more common tumor type with cartilaginous elements in the parapharyngeal space (and most common overall) is pleomorphic adenoma. However, with adequate sampling the transition to the typical admixture of ducts and myoepithelial cells will be recognized. Primary cartilaginous neoplasms (chondrosarcoma, chondroma) are theoretical considerations as well. Teratomas may have normal cartilage but are germ cell neoplasms with other elements.

Incidental findings such as cartilaginous choristoma in the context of intraoperative assessment of tonsils to find an occult primary will most assuredly be more common as the use of transoral robotic surgery becomes more widespread. Frozen section evaluation of TORS specimens is commonly utilized for diagnosis and margin assessment. While current ASCO recommendations are to submit TORS specimens in their entirety for frozen section, realistically this is not always feasible nor is it desirable given the risk of damaging or cutting through tumor. Accuracy of frozen section for identifying primaries is variable (50-90%) and can be skewed by inclusion of grossly obvious tumors to inflate performance. Here, the entire specimen consisted of four blocks and would not have been challenging to freeze in toto, but the multidisciplinary decision was to examine a representative section with the intent to preserve the remainder for higher quality permanent sections. Ironically, the discontiguous foci of tumor spanning 5 mm in this case were identified in a non-fibrous area on permanent sections. Whether they would have been identified or cut through if the entire specimen were frozen is speculative.

References

Berry J., Fibrochondroma of the tongue, Trans Pathol Soc Lond. 1890; 41: 81
Kannar V, Prabhakar K, Shalini S. Cartilaginous choristoma of tonsil: A hidden clinical entity. J Oral Maxillofac Pathol. 2013;17:292–3.
Arora S, Agrawal M, Nazmi M, Kapoor NK. Histological study of routine tonsillectomy specimen. Indian J Otolaryngol Head Neck Surg. 2008 Dec;60(4):309-13.
Çiriş IM, Erkılınc G, Kursat Bozkurt K, Karahan N, Yasan H, Sivrice ME. Cartilaginous choristomas in tonsillectomy specimen: A prospective analysis. Int J Pediatr Otorhinolaryngol. 2019 Jul;122:191-195.
Maghami E, Ismaila N, Alvarez A, Chernock R, Duvvuri U, Geiger J, Gross N, Haughey B, Paul D, Rodriguez C, Sher D, Stambuk HE, Waldron J, Witek M, Caudell J. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline. J Clin Oncol. 2020 Aug 1;38(22):2570-2596. doi: 10.1200/JCO.20.00275. Epub 2020 Apr 23. PMID: 32324430.

Quiz Answers

Q1 = C. Choristoma

Q2 = A. Pleomorphic adenoma

Contributors

John Grove, DO
Resident Physician, Department of Anatomic & Clinical Pathology
University of Pittsburgh Medical Center

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

Head & Neck Case Review 2023-01

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