A Rare Case of Sinonasal Lymphoepithelial Carcinoma Presented With Clinically Stage IV Disease.

Sinonasal lymphoepithelial carcinoma (SLEC) is an extremely rare malignancy. We present a case of SLEC in a 77-year-old man who presented with nasal congestion and persistent sinusitis. Imaging revealed a large right nasal mass involving right paranasal sinuses along with bulky bilateral cervical lymphadenopathy. In addition, there was a fluorodeoxyglucose avid L1 vertebral lesion. Biopsy of nasal mass and cervical lymph nodes showed syncytial growth of tumor cells in a lymphoplasmacytic background. Immunohistochemical stains showed positivity for pankeratin, CK5/6, epithelial membrane antigen, p40 (focal), and p63 (focal). An Epstein-Barr virus-encoded RNA by in situ hybridization was strong and diffusely positive. Based on these pathologic findings and considering the location of tumor, diagnosis of SLEC was rendered. L1 vertebral body lesion was clinical and radiologically considered to be a metastasis. Correlation with radiology to determine the exact location of tumor is extremely important for correct diagnosis due to its histopathologic similarities with relatively more common undifferentiated type of nasopharyngeal carcinoma. No standard treatment protocol has been established for this tumor yet. To our knowledge, this is first ever report of SLEC presented with clinical stage IV disease.

Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features.

ABSTRACT: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.

Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported. METHODS: The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC. RESULTS: A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively. CONCLUSIONS: The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

Pathologic grading of mucoepidermoid carcinomas of the salivary gland and its effect on clinicopathologic follow-up: an institutional experience.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Differences inprognosis can be noted owing to the tumor grade determined using multiple grading schemes (2-tier: low- and high-grade vs. 3-tier: low-, intermediate-, and high-grade). We studied clinicopathologic features of MEC using a 3-tier grading system and retrospectively categorized cytologic diagnoses as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).A total of 69 cases of MEC were identified, and most were seen in the parotid gland. Aggressive clinical behavior was seen in high-grade MEC compared with intermediate- and low-grade MEC. By fluorescence in situ hybridization (FISH) analysis, MAML2 rearrangements were seen in 78% of cases.The MSRSGC subcategorized the majority (63.8%) of MEC as salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, or malignant. Clustering intermediate- with low-grade cases did not significantly impact the clinical behavior. Both high-grade and oncocytic MEC can be MAML2 FISH negative.

Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck.

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs. METHODS: Submandibular gland FNA cytology specimens from 15 international institutions (2013-2017) were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. A correlation with the available histopathologic follow-up was performed, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The case cohort of 734 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 21.4% (0%-50%); nonneoplastic, 24.2% (9.1%-53.6%); AUS, 6.7% (0%-14.3%); benign neoplasm, 18.3% (0%-52.5%); SUMP, 12% (0%-37.7%); SM, 3.5% (0%-12.5%); and malignant, 13.9% (2%-31.3%). The histopathologic follow-up was available for 333 cases (45.4%). The ROMs were as follows: nondiagnostic, 10.6%; nonneoplastic, 7.5%; AUS, 27.6%; benign neoplasm, 3.2%; SUMP, 41.9%; SM, 82.3%; and malignant, 93.6%. CONCLUSIONS: This multi-institutional study shows that the ROM of each MSRSGC category for submandibular gland FNA is similar to that reported for parotid gland FNA, although the reported rates for the different MSRSGC categories were variable across institutions. Thus, the MSRSGC can be reliably applied to submandibular gland FNA.

Mucoepidermoid carcinoma, acinic cell carcinoma, and adenoid cystic carcinoma on fine-needle aspiration biopsy and The Milan System: an international multi-institutional study.

BACKGROUND: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC). MATERIALS AND METHODS: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up. RESULTS: A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa. CONCLUSIONS: The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management.

The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimens.

OBJECTIVE: To perform a retrospective investigation of our institutional experience with salivary gland fine needle aspirations (FNA) through the framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and assess the risks of neoplasm and malignancy for each diagnostic category. METHODS: All salivary gland FNAs performed from January 2009 to December 2016 were retrospectively categorised according to the MSRSGC. When available, pre-operative cytological results were correlated with subsequent histological follow-up. RESULTS: In total, 893 FNAs were reviewed. The specimens were retrospectively classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was available for 429 cases (48%); the majority (68.1%) were benign. The risks of neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN: 42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%, 78.9%; and M: 100%, 98.5%. CONCLUSIONS: The MSRSGC is a useful classification scheme for stratifying salivary gland lesions according to their associated risk of malignancy and guiding clinicians toward appropriate management. Diagnostic pitfalls are seen in a small proportion of cases and a multidisciplinary approach for assessing salivary gland pathology is essential in their evaluation.

Stability of Values for the Activities of Critical Enzymes Assayed in Serum Frozen for Prolonged Time Periods.

OBJECTIVES: Our medical center laboratory receives frozen clinical chemistry samples from outlying hospitals for which assays for critical enzyme activities are requested. Our objective is to determine the effects of freezing (-20°C) on these enzyme activities in samples over a one month period. METHODS: Enzyme activities for ALP, AST, ALT, CK and LD for 30 patient's sera were stored at-20°C and were assayed on a Beckman-Coulter AU5800 analyzer at 0, 15 and 30 days after collection. Statistical tests were performed to determine if the values were statistically the same or different. RESULTS: F-tests for all five enzyme levels showed no statistically significant differences (p>>0.05); linear regression analysis showed high correlation of results (r>0.99 for all correlations) with some bias for ALT. CONCLUSIONS: We conclude that the activities of these enzymes are stable, except possibly ALT, when stored frozen at -20°C over the 15- and 30-day storage periods.

Papillary Thyroid Microcarcinoma: Reclassification to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): a Retrospective Clinicopathologic Study.

Papillary thyroid microcarcinoma (PTMC) accounts for nearly 50% of newly diagnosed PTC cases. There is considerable debate in literature about the clinicopathologic features and prognostic significance of PTMC and whether it should be treated as a separate entity. Due to lack of agreement and supportive data, the consensus study group that established the criteria for non-invasive thyroid neoplasm with papillary-like features (NIFTP) kept its size above 1 cm i.e., excluding PTMC from this new group. As a result, to date, some patients diagnosed with PTMC get aggressive treatments such as partial or total thyroidectomy and even radioactive iodine ablation. We retrospectively studied clinicopathologic features and long-term follow-up of 48 cases of papillary thyroid microcarcinoma. Of these, 7 cases (15%) had capsular invasion, 2 cases (4%) had extrathyroidal extension, 1 case (2%) had lymphovascular invasion, 5 cases (25%) had lymph node metastases, no case (0%) had any distant metastases, and 1 case had recurrence after long-term follow-up (mean 13.7 years, range 1-21 years). Upon slide review, 8 cases fulfilled the criteria for NIFTP and were sub-classified under this new category. These 8 cases had no recurrence after long-term follow-up (mean 12.1 years, range 7-19 years). In this study, we confirmed the previous published reports exhibiting indolent nature of PTMC and also suggested that PTMC cases that fulfill all the criteria for NIFTP can be sub-classified under this term in order to avoid unnecessary aggressive treatment.

Mitochondrial Iron Accumulation in Parietal and Chief Cells in Iron Pill Gastritis Following Billroth II Gastrectomy: Case Report Including Electron Microscopic Examination.

Iron pill gastritis has been shown to be associated with superficial gastric erosion and deposition of iron in lamina propria and gastric antral glands. However, iron absorption in gastric parietal and chief cells is rare. We present a case of a 62-year-old man with iron deficiency anemia. His past medical history is significant for Billroth II surgery. His medications include ferrous sulphate 325mg. Esophagogastroduodenoscopy showed diffuse circumferential abnormal mucosa at the gastro-jejunal anastomosis. The mucosa was erythematous and violaceous. Biopsy showed reactive gastropathy with iron deposits predominantly in macrophages, parietal cells, and chief cells. These findings were confirmed by iron stain and later by electron micrography of the gastric mucosa that showed iron deposits in mitochondria and cytoplasm of the parietal and chief cells.

Crohn's disease presenting as gastric outlet obstruction: a therapeutic challenge?

Isolated gastric Crohn's disease with initial presentation related to gastric outlet obstruction is an unusual clinicopathological entity. We undertake here a literature review of this rare initial presentation of isolated gastric Crohn's disease and discuss the formidable diagnostic and therapeutic challenges encountered in such patients.

Cardiac Amorphous Tumour (CAT) Presenting with Thrombocytopenia.

Cardiac calcified amorphous tumour (CAT) is a rare non-neoplastic lesion with only a few cases reported in literature. We present an interesting case of CAT that was associated with unexpectedly low platelet count. A 40-year man presented with shortness of breath on exertion. Echocardiogram showed a mobile mass within the right atrium. Mass was surgically excised. His platelet count varied from 26,000/ul to 54,000/ul before surgery, which increased postoperatively. Histopathological examination revealed amorphous mass of eosinophilic fibrin with dense calcification. No morphologic evidence of myxoma was seen and the final diagnosis of CAT of the heart was rendered. CAT is a rare cardiac lesion with an excellent prognosis after complete surgical removal. The microscopic examination is the only tool for definitive diagnosis.

Solitary Fibrous Tumor of the Stomach.

Solitary fibrous tumor is a rare mesenchymal neoplasm that usually originates from the pleura, but has been reported in other extrapleural locations. We report a rare case of a solitary fibrous tumor of the stomach, which was successfully treated with endoscopic mucosal resection.

Cytomegalovirus Colitis in Immunocompetent Patients.

Cytomegalovirus colitis is common in immunocompromised patients, but rare in immunocompetent patients. The present study not only represents the colonoscopy and pathological findings, but also applies the method of diagnosing and treating cytomegalovirus colitis in immunocompetent patients.

Encapsulated classic and follicular variants of papillary thyroid carcinoma: comparative clinicopathologic study.

OBJECTIVE: To compare the clinicopathologic features of papillary thyroid carcinoma classic variant (PTC-CV) and papillary thyroid carcinoma follicular variant (PTCFV), with a focus on the encapsulated form. METHODS: In a retrospective search of computerized pathology files for 1996 to 1998, a cohort of 114 cases (58 cases of PTC-CV and 56 cases of PTC-FV) were selected for this study. Clinicopathologic data and long-term follow-up (serum thyroglobulin measurements, radiologic studies, and additional tissue sampling) through the date of compilation of study data were extracted from the medical records. RESULTS: The median patient age at initial diagnosis was 46 years for the PTC-CV group and 45.5 years for the PTC-FV group. Complete tumor encapsulation was seen in 40 PTC-CV cases (69%) and in all PTC-FV cases (100%). A higher rate of tumor capsule invasion (CI), lymphovascular invasion (LVI), extrathyroidal extension, and lymph node metastatic lesions was seen in PTC-CV than in PTC-FV: CI, 26% versus 18%; LVI, 17% versus 4%; extrathyroidal extension, 19% versus 7%; and lymph node metastatic lesions, 68% versus 29%. Clinical, radiologic, or pathologic follow-up data were available in 36 PTC-CV cases (62%) and 34 PTC-FV cases (61%). The median duration of follow-up for the PTC-CV group was 10 years and for the PTC-FV group was 9 years. Tumor recurrence was found in 10 patients with PTC-CV (28%) and 2 with PTC-FV (6%). Distant metastatic lesions occurred in 3 patients with PTC-CV (8%) and 1 patient with PTC-FV (3%) (P = .17); of these, 2 cases of PTC-CV were encapsulated and showed CI, LVI, and lymph node metastatic lesions. CONCLUSION: Our current study confirms previous reports that both encapsulated PTC-CV and encapsulated PTC-FV are indolent tumors and are associated with very low mortality.