Application of the Milan system for reporting salivary gland cytopathology to core needle biopsies of the parotid gland.

AIMS: The Milan system for reporting salivary gland cytopathology was developed by an international group of experts and first published in 2018 with the goal to standardise reporting of salivary gland aspirates. Seven categories with distinct risks of malignancy were proposed. Core needle biopsies (CNB) of salivary glands are also common, but reporting lacks standardisation. Here we explore the feasibility of a Milan-like reporting system on CNB of the parotid gland. METHODS AND RESULTS: Our laboratory information system was searched for parotid gland CNBs from 2010 to 2021. Reports were translated into a Milan-like reporting system. When available, CNB findings were correlated with cytology and resection specimens. In order to compare the performance of CNB with fine-needle aspirations (FNA), we established a second cohort of cases consisting of parotid FNA with surgical follow-up. The risk of neoplasia (RON) and risk of malignancy (ROM) was calculated for FNA and CNB Milan categories using cases with follow-up resection. We analysed 100 cases of parotid gland CNB. Of these cases, 32 underwent subsequent resection, while 52 had concurrent FNA. A total of 20 cases had concurrent FNA and underwent follow-up resection. In 63 (63%) cases, a specific diagnosis was provided on CNB, with 18 cases undergoing follow-up resection having an accuracy rate of 94%. CONCLUSIONS: This study confirms the feasible of using a Milan-like system in the setting of parotid gland CNB with differentiation in RON and ROM. CNB allows assessment of architectural features that may allow more specific diagnoses in some cases.

The Increasing Problem of Syphilis Manifesting as Head and Neck Cancer: A Case Series.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum. Rates have been rising in the US and globally. Known as the "Great Imitator," syphilis can involve head and neck subsites, and often can masquerade as possible carcinoma of the head and neck. Here, we present three distinct cases of syphilis presenting as suspected head and neck malignancy involving the oropharynx, larynx and oral cavity. All cases were diagnosed on surgical pathologic examination of diseased tissues and treated. It is important for practicing otolaryngologists to understand head and neck manifestations of syphilis to facilitate proper diagnosis and treatment. Laryngoscope, 134:236-239, 2024.

Challenging differential diagnoses in small biopsies from the sinonasal tract.

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

Fine needle aspiration biopsy of epithelioid-mesenchymal neoplasm with PTCH1-GLI1 fusion: A case report.

Mesenchymal tumors harboring GLI1 gene fusions are a rare new entity that typically occur in the head and neck region of young to middle aged adults, with a particular predilection for the tongue. We report herein a case of epithelioid mesenchymal tumor with PTCH1-GLI1 gene fusion of the right submental region in an 82-year-old male never smoker. Ultrasound-guided fine needle aspiration (FNA) with concomitant core needle biopsy was performed. Cytology smears revealed a hypercellular, monotonous aspirate comprised of epithelioid to plasmacytoid cells with round regular nuclei and moderate amounts of cytoplasm. There were admixed granulomata. The patient underwent surgical resection with limited neck dissection and subsequent pathologic examination with performed next generation sequencing confirmed the presence of epithelioid mesenchymal tumor with PTCH1-GLI1 gene fusion. To our knowledge, this is the first reported example of a mesenchymal tumor harboring GLI1 gene fusion initially evaluated by FNA.

ROC analysis of p16 expression in cell blocks of metastatic head and neck squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma is associated with human papillomavirus (HPV) and often presents with early metastasis to cervical neck lymph nodes that are amenable to fine-needle aspiration (FNA). The most common method of HPV status determination is p16 immunohistochemistry (IHC). The literature suggests that a lower threshold is needed for p16 positivity on cell block. We examined and quantified p16 IHC staining on cell block and used receiver operating characteristics (ROC) curve analysis to determine an optimal cutoff value with high sensitivity and specificity. METHODS: Thirty-six FNAs of metastatic squamous cell carcinoma from cervical lymph nodes with p16 IHC were evaluated. The p16 stain was quantified in 5% increments and high-risk HPV mRNA in situ hybridization was performed as a gold standard test. Statistical analysis was performed. RESULTS: Interobserver variability was evaluated and was shown to be low with an intraclass correlation coefficient of 0.857. ROC analysis was performed and showed that a cell block p16 IHC cutoff of 15% yielded the highest sensitivity (80%) and specificity (81.8%). CONCLUSION: Our data show that a threshold of 15% p16 staining in cell block maximizes sensitivity and specificity.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia in conjunction with parotid basal cell adenoma: Cytologic, histologic, and molecular features.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare malignancy in the thyroid: only 56 cases with histologic descriptions are reported in the literature and fewer reports describe the cytomorphology. Given the rarity of SMECE, data on the cytomorphologic and molecular features are limited. We report a case of a 53-year-old woman with a 5 cm left thyroid mass. Fine-needle aspiration (FNA) revealed atypia of undetermined significance and pathology of left thyroid lobectomy specimen showed SMECE. Additionally, a left pre-auricular lump was noted and FNA followed by left superficial parotidectomy showed basal cell adenoma. Next-generation sequencing showed point mutations in NTRK3 and NF1. Unlike salivary gland mucoepidermoid carcinoma, MAML2 translocations are not present in SMECE. Even though it is a rare entity, awareness of SMECE of the thyroid is important. In this case report we review the cytomorphologic, histologic, and molecular features.

The utility of high-risk human papillomavirus E6/E7 mRNA in situ hybridization in assessing HPV status on cell block.

INTRODUCTION: Assessment of human papillomavirus (HPV) status is critical to the treatment and prognosis of patients with oropharyngeal squamous cell carcinoma. Patients often present with enlarged cervical lymph nodes which are amenable to fine needle aspiration (FNA) and cell block creation. The most widely used method for assessing HPV status is the surrogate marker p16. Other HPV specific methods such as high-risk HPV E6/E7 mRNA in situ hybridization (ISH) have been shown to perform as well as p16 and are easier to interpret. Our study evaluates the utility of high-risk HPV mRNA ISH in cell block specimens. METHODS: Thirty-six cases of metastatic squamous cell carcinoma in cervical neck lymph node FNAs were identified over a 3-year period. All cases had p16 immunohistochemistry (IHC) performed on cell block. HR HPV mRNA ISH was performed on the cell block and compared to the p16 results. Additionally, p16 and HR HPV mRNA ISH status was assessed in those cases with corresponding surgical resections. RESULTS: HR HPV mRNA ISH confirmed the p16 IHC (either positive or negative) in 24 of the 36 cases (66.7%). Six false negative cases were p16 negative/HR HPV mRNA ISH positive. HR HPV mRNA ISH was positive in 75% of the four p16 equivocal cases. Two cases were p16 positive/HR HPV mRNA ISH negative. CONCLUSIONS: HR HPV mRNA ISH is no more difficult to perform in the IHC lab and is easier to interpret than p16 IHC. HR HPV mRNA ISH is a useful alternative to p16 in cell block specimens.

Long-Term Maintenance of Acinar Cells in Human Submandibular Glands After Radiation Therapy.

PURPOSE: In a combined retrospective and prospective study, human salivary glands were investigated after radiation treatment for head and neck cancers. The aim was to assess acinar cell loss and morphologic changes after radiation therapy and to determine whether irradiated salivary glands have regenerative potential. METHODS AND MATERIALS: Irradiated human submandibular and parotid salivary glands were collected from 16 patients at a range of time intervals after completion of radiation therapy (RT). Control samples were collected from 14 patients who had not received radiation treatments. Tissue sections were analyzed using immunohistochemistry to stain for molecular markers. RESULTS: Human submandibular and parotid glands isolated less than 1 year after RT showed a near complete loss of acinar cells. However, acinar units expressing functional secretory markers were observed in all samples isolated at later intervals after RT. Significantly lower acinar cell numbers and increased fibrosis were found in glands treated with combined radiation and chemotherapy, in comparison to glands treated with RT alone. Irradiated samples showed increased staining for duct cell keratin markers, as well as many cells coexpressing acinar- and duct cell-specific markers, in comparison to nonirradiated control samples. CONCLUSIONS: After RT, acinar cell clusters are maintained in human submandibular glands for years. The surviving acinar cells retain proliferative potential, although significant regeneration does not occur. Persistent DNA damage, increased fibrosis, and altered cell identity suggest mechanisms that may impair regeneration.

Primary Dedifferentiated Amelanotic Anorectal Melanoma: Report of a Rare Case.

Anorectal melanoma (ARM) is an uncommon aggressive malignancy that comprises 0.5% to 1.6% of all melanoma manifestations. Dedifferentiated melanoma is very rare with loss of all melanocytic differentiation markers and is usually seen in metastatic melanoma of cutaneous origin. In this article, we report the first case of primary dedifferentiated amelanotic ARM in a 68-year-old male who presented with anal discomfort that was initially treated as inflamed hemorrhoids. Physical examination revealed a large protruding anal mass, biopsy of which showed biphasic malignant tumor cells with distinct immunoprofiles: a superficial spindled/sarcomatoid component positive for SOX10 and S100, and a deeper epithelioid/rhabdoid component positive for desmin, AE1/AE3, and EMA. Both components were negative for HMB-45, Melan-A/MART-1, c-Kit, and other lineage markers. Molecular analysis by polymerase chain reaction demonstrated wild-type BRAF and KRAS genes. A diagnosis of dedifferentiated ARM was made based on the coexistence of a differentiated component (spindled: S100 and SOX10 positive) and a dedifferentiated component (epithelioid: all melanoma markers including S100 and SOX10 negative). Shortly afterwards, the patient developed extensive pulmonary and liver metastases and expired 20 days after the diagnosis was rendered, reinforcing the highly aggressive nature of this disease entity.