Epithelial Membrane Antigen Positivity Research Articles

Epidemiology, symptomatology, diagnosis and clinical implications of cystic tumors of atrioventricular node (CTAVN): A systematic review.

e23561 Background: Primary cardiac tumors have an incidence of 0.0017% to 0.03% of all autopsies. CTAVN is a rare tumor associated with sudden cardiac death, and its incidence cannot be accurately determined as the diagnosis has been historically made on incidental or intentional autopsy with careful microscopic examination of the conduction system. To date, no systematic evaluation has been made of its clinical outcomes and diagnosis methods; hence, we sought to perform a systematic analysis based on available literature. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus. Studies with a confirmed pathological diagnosis of CTAVN were included. All statistical analyses were conducted on R version 4.1.2. Results: 34 studies with 42 patients with a diagnosis of CTAVN were included. A significant majority of patients were female (n = 29,69%), mean age (±SD) of patients was 47.7 ± 9.33 years. Dyspnea was the most commonly reported symptom among 12 patients (28.5%), followed by palpitations (10,23.8%), syncope (6,14.2%), chest pain (6, 14.2%), dizziness (4,9.5%) and, fatigue (3,7.1%). Third-degree AV block was the most common EKG finding (11,26.1%), followed by first-degree (8, 19.0%) and ventricular fibrillation (n = 2, 4.6%). Transthoracic, transesophageal echo, and cardiac MRIs were done in the majority of the patients. The tumors were most commonly located in the lower part of the interatrial septum in 33% (14), AV node (13, 30.9%), followed by tumors involving both AVN and proximal His bundle/interventricular septum (7, 16.67%). Histopathologically, multiple different lining epithelia were reported: cuboidal cell lining (18, 42.8%), squamous lining (6, 14.2%) and transitional lining (7, 16.6%), most of the tumors (n = 15, 30.9%) were endodermal in origin. Immunohistochemically, 38% of patients had positive epithelial membrane antigen. 45.2% of patients were positive for carcinoembryonic antigen. Cytokeratin was positive in 47.6% of the tumors. Due to varying degrees of AV block, a significant number of patients required pacemaker implantation (13, 30.9%), and 1 patient required intracardiac defibrillator placement. In 9 patients (21.4%), the AV nodal cystic tumor was surgically removed. 21/42 patients were alive; mortality due to CTAVN was reported in 10(23.8) percent of patients. Causes of mortality included cardiac complications (8,19%), respiratory complications (5,11.9%), central nervous system complications (2, 4.7%), sepsis (2,4.7%), and surgical complication (1, 2.3%) Conclusions: To our knowledge, this is the first and largest review on CTAVN. This review contributes valuable insights into the diagnosis, histopathology, and management of cystic tumors of the AV node, offering a foundation for further research on workup, clinical considerations, and treatment of this rare cardiac pathology.

Dendritic Cell Neurofibroma with Pseudorosette: An Uncharted Entity at Unusual Sites: Two Case Reports with Literature Review

Dendritic cell neurofibroma with pseudorosette (DCNP) is a novel entity of neurofibroma with sparse literature. Neurofibroma is a benign peripheral nerve sheath tumor having many known histological variants including localized, diffuse, plexiform, solitary, cellular, and atypical forms, all of which lead an indolent course. Like other forms of neurofibroma, DCNP usually is located in the dermis or deeper soft tissue or within the nerve trunk. It reveals a characteristic histomorphology of distinct multiple nodules comprising two types of cells: the outer lymphocyte like dark Type I cells (Schwann cell-like) forming pseudorosettes surrounding the inner scattered lighter and larger Type II cells (ganglion/dendritic cell-like). Although histogenesis of these two type of cells is debatable, immunopositivity for S100 suggests the neuronal origin and the fibrous pseudocapsule covering tumor nodules being immunopositive to epithelial membrane antigen (EMA) suggests perineurium. Here, we report two such cases of DCNP at two different yet unusual sites of cervical and perianal regions. Neither patient nor their family members had any features of neurofibromatosis(NF 1). Both the cases were adults, presented with firm nontender subcutaneous nodules of long duration causing pressure symptoms. Those were resected and evaluated for microscopy. Histomorphology aided by immunohistochemistry positivity for S100 and EMA confirmed DCNP. Follow up study after half an year of surgery was uneventful and Patients were found to be relieved of all symptoms. We present this unusual new variant that poses challenge for it’s close histological mimickers like cellular/epithelioid schwannoma and plexiform neuroma and yet want to emphasize the innocuous behavior of tumor that can be cured by surgical resection.

Secretagogue effect of PDE4 inhibitor apremilast on human salivary gland organoids obtained from primary Sjögren's syndrome patients.

The aim of the study was to culture vital salivary gland organoids obtained through labial or parotid biopsy of primary Sjögren's syndrome (pSS) patients in order to evaluate their morphological and functional features in basal condition and after stimulation with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activator forskolin and phosphodiesterase 4 (PDE4) inhibitor apremilast, their in vitro regenerative capacity and the immune-histological resemblance with original tissue. Salivary gland tissues from five pSS patients were processed to obtain vital organoids; swelling assay and cell proliferation tests were performed after forskolin and apremilast application. Immunochemistry evaluation on original salivary gland tissue and corresponding organoids was performed, and secretomics analysis was conducted to assess their functional status. After application of forskolin and apremilast, we observed organoid swelling after 30 minutes, compatible with a positive functional status and enhancement of saliva production. In 3 cases, apremilast induced organoid proliferation. All cases were positive for cytokeratin 14 (CK14) and most for cytokeratin 5 (CK5). All the cases were positive for amylase; its secretion, and thus functional status of organoids, was confirmed by its high concentration in the culture medium. A focal ductal differentiation was found in some cases, highlighted by epithelial membrane antigen (EMA) positivity. The more differentiated EMA positive areas were negative for the staminal marker CK14, showing a sort of "complementary staining". Our data highlighted that differentiated cells and vital functional organoids that recapitulate the development of original salivary glands can be obtained from pSS epithelium. For the first time, the direct stimulating effect of PDE4 inhibitor apremilast on pSS human salivary gland organoids is reported, opening new perspectives on targeting oral dryness with drugs that combine secretagogue and immunomodulatory effects.

What is new in intraneural perineurioma?

Since the initial description of intraneural (IN) perineurioma in 1964, advances in the understanding of the clinical presentation, diagnostic imaging, pathologic features, and genetic underpinnings have changed how this pathology is managed. IN perineuriomas are rare, benign peripheral nerve sheath tumors, most frequently coming to clinical attention when patients present with painless, progressive weakness or sensory loss in adolescence or young adulthood. The gold standard of diagnosis has traditionally been with targeted tissue biopsy demonstrating "pseudo-onion bulb" formation with positive epithelial membrane antigen (EMA) staining. However, modern magnetic resonance imaging is allowing some patients to forgo biopsy. Recent genetic studies of IN perineuriomas have demonstrated common TRAF7 point mutations and rare NF2 mutations, which may present targets for diagnosis or therapy in the future. Current advances have allowed for us to provide improved patient counseling with informed understanding for various clinical scenarios. With the workup and diagnosis now clearly defined, the next frontier is for improving the lives of patients with IN perineuriomas through the interaction between restoration of functional deficits and advances in our understanding of the genetics of this entity.

CPC12 Coinheritance of BRCA2 and CYLD germline pathogenic variants associated with targetable metastatic malignant cylindroma

Abstract CYLD cutaneous syndrome (CCS) presents during puberty with the development of hair follicle tumours, including cylindromas, spiradenomas or trichoepitheliomas, and is associated with pathogenic variants in the tumour suppressor gene CYLD. Germline pathogenic variants of BRCA2 are associated with an increased risk of breast, ovarian, pancreatic and prostate cancer. Coinheritance of pathogenic variants in both genes has not been previously reported, and here, we present a 29-year-old man with metastatic malignant cylindroma, where knowledge of the germline variants has targetable therapeutic implications. The proband presented with cylindromas on his scalp from the age of 8 years, inherited from his mother who had CCS. The proband’s father and paternal grandmother both had early-onset breast cancer. The proband’s 33-year-old sister had been diagnosed with breast cancer and CCS; genetic testing revealed germline pathogenic variants in both BRCA2 and CYLD. Aged 28 years, the proband presented with a growing, ulcerated cylindroma on the scalp. Histology revealed a biphasic neoplasm, showing malignant cylindroma with high-grade features arising within a pre-existing benign cylindroma. The malignant epithelioid component of the tumour showed brisk mitotic activity (25 mitoses per mm2) and large infiltrative nests with central comedo-type necrosis. Immunohistochemistry showed positivity for epithelial membrane antigen, CK7, p63 and patches of CK5/6, whereas carcinoembryonic antigen, S100 and human melanoma black-45 were negative. Several weeks after excision of the malignant scalp cylindroma, a lump presented on the left side of the patient’s neck; biopsy revealed histology consistent with the malignant scalp cylindroma. Radiological imaging revealed metastatic deposits of malignant cylindroma in the right axilla, both lungs and the brain. Genetic testing of the proband revealed germline pathogenic variants in both BRCA2 and CYLD, as seen in his sister. The patient received radiotherapy for the tumour in his neck, with partial resolution of symptoms and gamma-knife ablation of brain metastases. DNA extracted from the patient’s tumour was analysed using a high-resolution single-nucleotide polymorphism array, which demonstrated loss of heterozygosity including the BRCA2 and CYLD loci. The germline and somatic pathogenic variants in this patient support the use of unlicensed therapeutics that target BRCA deficiency, such as poly-ADP ribose polymerase inhibitors, which have not previously been used to treat malignant cylindroma. This case emphasizes the importance of recognizing coinheritance of tumour suppressor genes in rare genetic conditions, as this can provide novel management options and improve patient outcomes.

P11.39.B An unusual case of astroblastoma in adult: a case report and review of the literature

Abstract Background Astroblastoma is an uncommon glial neoplasm of controversial histogenesis, clinical behavior and response to treatment yet to be understood. It usually appears in the cerebral hemisphere of young patients, preferably in the frontal and parietal lobes. Histologically, its characteristics overlap with high-grade gliomas, making the differential diagnosis between these entities complex. Clinical, radiological, histopathological correlations and, if necessary, genetic tests (MN1 Rearrangement) are essential for an accurate diagnosis. Material and Methods We present a case report based on data collected retrospectively from electronic medical records. Results A 63-year-old male with a 3-month history of headache and one episode of mental confusion. In the neurological exam, language alteration was noted and the other systemic exams were normal. Magnetic resonance imaging of the brain revealed an intra-axial expansive formation involving the insula, superior and middle temporal gyrus, left portion of brainstem, with lobulated contours and heterogeneous, solid-cystic appearance with intermingled hematic foci. The solid portion had heterogeneous contrast enhancement and foci of gross calcification. The lesion was resected and the postoperative MRI showed no residual tumor lesion. Histopathological evaluation showed an extensive pattern of perivascular pseudorosettes of astrocytic cells with broad processes radiating to central vessels, in addition to frequent foci of hyalinization. Immunohistochemistry showed positive staining with antibodies to glial fibrillary acidic protein (GFAP), vimentin and S100 protein, in addition to membranous positivity for epithelial membrane antigen (EMA). The Ki-67 index was 20%. Based on these data, the diagnosis of NOS astroblastoma was established. Four months after resection, imaging follow-up displayed enhancement of the surgical cavity, suggestive of local recurrence. The patient underwent three-dimensional conformal radiotherapy with a total dose of 6000cGy in 30 sessions, followed by adjuvant chemotherapy with temozolomide.The patient did not have tumor recurrence until the last follow-up made 16 months after surgery. Conclusion This is an atypical case of an extremely rare glial tumor of the central nervous system, since most patients with astroblastoma range from 3 months to 40 years (median: 15 years), which makes the diagnosis challenging.

SEBACEOUS CARCINOMA IN RETROMOLAR REGION: CASE REPORT

Sebaceous carcinoma is a rare malignant tumor derived from the adnexal epithelium of the sebaceous glands. A 58-year-old White male patient attended the stomatology service complaining about a "lump near the third molar." In the history of the current disease, the patient reported a lesion that appeared approximately 6 months ago and with painful symptoms. Intraoral examination showed a single erythematous tumor in the retromolar region with a smooth surface and ulcerated areas, diffuse borders, irregular, firm, fixed with an infiltrative characteristic, tender, and measuring 2.5 × 2.0 × 1.0 cm. An incisional biopsy was performed with clinical suspicion of squamous cell carcinoma. The histologic sections stained in hematoxylin-eosin and the immunohistochemical reaction showed positivity for epithelial membrane antigen, highlighting the vesicular pattern of the tumor cell cytoplasm. The final result was compatible with sebaceous carcinoma. The patient was referred to the oncology sector and is waiting for cancer treatment.

Low-grade Fibromyxoid Sarcoma of the Vulva and Vagina: Clinical, Pathologic, and Molecular Characterization of 7 Cases and Review of the Literature.

Low-grade fibromyxoid sarcoma (LGFMS) is a malignancy with propensity for late relapse that principally affects deep soft tissues of the extremities and trunk. Its occurrence in the lower female genital tract is rare, and thus it may not be always considered in the differential diagnosis. We describe the salient features of 7 vulvovaginal LGFMS identified in the authors' consultation files. Clinical information was obtained from referring pathologists. Archival slides were reviewed, and immunohistochemistry and fluorescence in situ hybridization were performed in cases with available material. Median age was 40 years (range, 34 to 58 y). Primary sites included vulva (n=6) and vagina (n=1). Tumors were 1.2 to 8.7 cm (median, 5.0 cm) in size and grossly circumscribed with firm to focally gelatinous cut surfaces. Microscopically, 5/7 had infiltrative edges. All tumors showed fibrous and myxoid areas, with lobulated myxoid foci in 5/7, comprising storiform, patternless, or (less often) fascicular arrangement of spindled to stellate cells with bland, slender to ovoid nuclei. In all cases, mitoses were <1/2.4 mm 2 , and necrosis was absent. Capillary "arcades" were seen in 3/7. Margins were positive in 3/6. Immunohistochemistry showed positive epithelial membrane antigen in 4/6 and MUC4 in 5/6. Fluorescence in situ hybridization detected FUS rearrangement in 5/7. Both tumors without FUS rearrangement were also negative for EWSR1 rearrangement. All 5 patients with available follow-up were alive and disease-free 10 to 150 months (median, 57 mo) after diagnosis. However, a review of vulvovaginal/pelvic LGFMS previously reported shows recurrences as late as 45 years after initial diagnosis. Pathologists need to be aware that LGFMS can arise in the vulvovaginal region. Tumor lobulation, capillary arcades, and positive MUC4 are helpful features distinguishing LGFMS from other bland myxoid spindle cell neoplasms in the lower female genital tract. Molecular testing can be useful in challenging cases. Complete excision is feasible for most vulvovaginal LGFMS. Long-term surveillance is required as local and/or distant spread can occur decades after diagnosis.

CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications

Meningiomas are common tumors of the central nervous system. Although their histological diagnosis is usually straightforward, their differential diagnosis versus other tumors may be challenging at times. The objective of this study is to assess the diagnostic value of CD13 immunoexpression in the differential diagnosis between meningiomas and their morphological mimics. Immunohistochemical analysis for CD13, epithelial membrane antigen, SOX10, and STAT6 was carried out in a large cohort of primary meningeal tumors comprising 225 meningiomas, 15 schwannomas, and 20 solitary fibrous tumor/hemangiopericytomas. Within the meningioma group, the expression of CD13 and epithelial membrane antigen was distinguished in three categories using a semiquantitative score. Most of meningiomas expressed CD13 (94%) and epithelial membrane antigen (96%) while none of the schwannomas nor of the solitary fibrous tumor/hemangiopericytomas was positive for either the two markers. Diffuse positivity for CD13 and epithelial membrane antigen was more common in low-grade meningiomas than in anaplastic ones, which were also more often negative for such markers, especially for CD13 (32%). CD13 is a helpful immunohistochemical marker for the differential diagnosis of meningiomas and their mimics, achieving in combination with epithelial membrane antigen maximal sensitivity (100%) and showing statistically relevant difference of expression in comparison with both schwannomas (p < 0.0001) and solitary fibrous tumor/hemangiopericytomas (p < 0.0001). Furthermore, loss of CD13 expression could be related to outcome as it is associated with worrisome histological findings, mainly in the setting of anaplastic meningiomas.

Head and Neck Low-Grade Fibromyxoid Sarcoma: A Clinicopathologic Study of 15 Cases.

Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon mesenchymal tumor usually arising in the lower extremities and trunk. Only rare examples in the head and neck region have been reported. Fifteen cases of head and neck LGFMS were retrieved. MUC4 was performed on all cases. Results for smooth muscle actins, β-catenin, desmin, S100 protein, Epithelial membrane antigen (EMA) and STAT6 immunohistochemistry, as well as FUS rearrangement status, were recorded when available. Sites included neck (8), supraclavicular region (4) and orbit (1), parapharyngeal space (1) and lower lip (1). The age of the patients ranged from 3 to 97years (median, 26years). Tumors displayed classical morphologic features of LGFMS, as described. All cases (15/15) were positive for MUC4, and all cases tested (4/4) harbored FUS rearrangement. Variable positivity for EMA was identified in one case. Follow-up was available in 11 patients, ranging from 2 to 240months (mean 71.4months; median, 44months). Three tumors recurred locally; none metastasized. In conclusion, although distinctly uncommon, LGFMS may arise in the head and neck region and should be distinguished from other more common spindle cell tumors in these locations. The morphologic, immunohistochemical and molecular genetic features of head/neck LGFMS are identical to those occurring elsewhere. The long-term metastatic risk of LGFMS in these locations remains to be fully elucidated.

Diagnostic utility of BRCA1-associated protein 1 (BAP1), Programmed Cell Death4 (PCD4) and Epithelial membrane antigen (EMA) expression in differentiation of malignant mesothelioma from reactive mesothelial cell hyperplasia in both cytology and cell block

Background: Malignant pleural mesothelioma (MPM) is the most lethal tumor arising from the mesothelial cells. Sometimes, it is difficult to be diagnosed based on morphology alone as reactive mesothelial hyperplasia (RMH) and some metastatic carcinomas may be confused with mesothelioma. Aim of the study: Our study aims to evaluate diagnostic utility of BRCA1 “Breast Cancer gene” associated protein-1 (BAP1), Programmed Cell Death (PCD4), and Epithelial membrane antigen (EMA) in differentiation of malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RMH) by immunohistochemistry (IHC).Material and methods: Retrospective study, include 60 patients, was carried out in Chest and Pathology Departments of Zagazig University from October 2016 till August 2020. The expression levels of BAP1, PCD4and EMA were investigated using cytological analysis compared with cell block method in all cases of MPMs and RMHResults: BAP1loss was detects malignant mesothelioma confirmed by cytology in 19 out of 20 patients with sensitivity of 95%, specificity 92.5%, PCD4 was positive in 39 out of 40 patients of RMH and can diagnose reactive mesothelioma with a sensitivity of sensitivity of 85.7%, specificity 100%. EMA was positive 95% in MM confirmed by cytology and can diagnose malignant mesothelioma with a sensitivity of 95%, specificity 97.5%. Conclusion: Increased sensitivity of diagnosis by cell block method was observed in cases that were reported as reactive mesothelial hyperplasia by conventional smears. BAP1 loss, negative PCD4 immunostaining and positive EMA favor mesothelioma.Keywords: BAP1, PCD4, EMA, malignant mesothelioma.

Do All Notochordal Lesions Require Proton Beam Radiotherapy? A Proposed Reclassification of Ecchordosis Physaliphora as Benign Notochord Cell Tumor.

Objectives Ecchordosis physaliphora (EP) is a benign notochord lesion of the clivus arising from the same cell line as chordoma, its malignant counterpart. Although usually asymptomatic, it can cause spontaneous cerebrospinal fluid (CSF) rhinorrhea. Benign notochordal cell tumor (BNCT) is considered another indolent, benign variant of chordoma. Although aggressive forms of chordoma require maximal safe resection followed by proton beam radiotherapy, BNCT and EP can be managed with close imaging surveillance without resection or radiotherapy. However, while BNCT and EP can be distinguished from more aggressive forms of chordoma, differentiating the two is challenging as they are radiologically and histopathologically identical. This case series aims to characterize the clinicopathological features of EP and to propose classifying EP and BNCT together for the purposes of clinical management. Design Case series. Setting Tertiary referral center, United Kingdom. Participants Patients with suspected EP from 2015 to 2019. Main Outcome Measures Diagnosis of EP. Results Seven patients with radiological suspicion of EP were identified. Five presented with CSF rhinorrhea and two were asymptomatic. Magnetic resonance imaging features consistently showed T1-hypointense, T2-hyperintense nonenhancing lesions. Diagnosis was made on biopsy for patients requiring repair and radiologically where no surgery was indicated. The histological features of EP included physaliphorous cells of notochordal origin (positive epithelial membrane antigen, S100, CD10, and/or MNF116) without mitotic activity. Conclusion EP is indistinguishable from BNCT. Both demonstrate markers of notochord cell lines without malignant features. Their management is also identical. We therefore propose grouping EP with BNCT. Close imaging surveillance is required for both as progression to chordoma remains an unquantified risk.

Intracerebral Calcifying Pseudoneoplasm of the Neuroaxis (CAPNON) Presenting with an Atypical Immunohistochemical Profile: Case Report and Review of the Literature

Background: Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a very rare benign lesion that can be located anywhere in the nervous system, with only 59 intracranial cases described. The general lack of knowledge about this lesion hinders its preoperative diagnosis. Despite the consistent image findings, the final diagnosis is only established based on anatomopathological and immunohistochemical studies. The lesion is more commonly positive for epithelial membrane antigen (EMA) and vimentin, and negative for glial fibrillary acidic protein (GFAP) and S-100, suggesting a leptomeningeal origin. The opposite, however, may also occur, although very rarely (just two cases positive for GFAP and negative for EMA and vimentin reported this far). The treatment consists of total resection of the lesion, which yields a good prognosis. Case Presentation: We report the case of a 23-year-old female who presented with disperceptive focal seizures, sometimes evolving to bilateral tonic-clonic seizures, starting at age 9. She had a nodular calcified lesion in the left precuneus and inferior parietal lobe. The lesion was completely resected, and the immunohistochemical study revealed positivity for EMA, vimentin, GFAP, and S-100. No case hitherto published was positive for all four markers. This atypical immunohistochemical profile of the CAPNON may suggest a dual origin of this lesion, both parenchymal and leptomeningeal. Conclusion: The general lack of knowledge of CAPNON makes this lesion underdiagnosed. Therefore, in the face of a calcified lesion in the nervous system, one should consider the possibility of a CAPNON among the differential diagnoses. The immunohistochemistry is undoubtedly an important tool, but the anatomopathological study, associated with image findings, remain the gold standard for the diagnosis of CAPNON.

Spindle cell carcinoma of the parotid- A rare case entity with review of literature

Spindle cell carcinoma of the salivary gland is very rare. Spindle cell carcinoma is a variant of squamous cell carcinoma with an aggressive course. We present a rare case of spindle cell carcinoma of the parotid in a54-year-old male, who presented with a rapidly enlarging mass in the right parotid gland. Histopathologically, the tumour was composed of foci of squamous cell carcinoma with sheets of malignant squamoid cells and spindle cell sarcoma with scattered pleomorphic, plump to spindle- shaped cells with foci of bone formation. Immunohistochemical studies revealed cytokeratin positivity and vimentin negativity in the squamous cell carcinoma component with focal positivity for epithelial membrane antigen and negative expression of cytokeratin and vimentin positivity in the sarcomatoid component. A final diagnosis of primary spindle cell carcinoma of the parotid gland was given. Our patient is alive and well with no clinical or radiological evidence of recurrence or metastatic disease after 12 months of follow up period.

Small Cell Carcinoma of the Ovary: Clinicopathologic and Immunohistochemical Analysis of 7 New Cases of a Rare Malignancy

Small cell carcinoma of ovary (SCCO) is extremely rare. Two types of SCCO are recognized, the pulmonary type (SCCOPT) and the hypercalcemic type (SCCOHT). Establishing an accurate diagnosis is challenging, owing to its rarity and paucity of data describing the distinctive histopathologic and immunohistochemical (IHC) features. This was a retrospective study conducted over a period of 4 years. All cases reported as SCCO on histopathology were retrieved. All the available clinical, histopathological, and IHC features were studied in detail. A total of 7 cases of SCCO were diagnosed during the study period. There were 4 cases of SCCOPT and 3 cases of SCCOHT and with mean age of 57.25 and 22 years, respectively. All the cases presented as stage IV disease. Among the SCCOPT cases, 3 showed bilateral involvement with 1 showing concurrent uterine endometrioid adenocarcinoma. Microscopy revealed small hyperchromatic cells with brisk mitosis and multifocal necrosis. On IHC, these were consistently positive for chromogranin, CD56, and synaptophysin. All the SCCOHT cases showed unilateral involvement. Microscopically, in addition to small hyperchromatic cells, larger "rhabdoid" tumor cells were also seen. On IHC, chromogranin was negative, with positivity for vimentin and epithelial membrane antigen. The expression of SMARCA4/BRG1 was lost while SMARCB1/INI1 was retained in all cases. All of these patients developed recurrence and died due to disease progression despite treatment. SCCO is an extremely infrequent ovarian malignancy with poor prognosis. Knowledge about its characteristic features is important for accurate tissue diagnosis and appropriate management.

Chapter 5 - Pathology of meningiomas

Meningiomas are a diverse group of neoplasms that exhibit a wide range of morphologies and clinical behavior. They are generally accepted to originate from arachnoid cap cells within the leptomeninges. Classic histologic features include whorl formations, psammoma bodies, nuclear holes, and nuclear pseudoinclusions. Meningiomas are classified as benign, atypical, or anaplastic (grades I, II, or III) based on histologic features including mitotic activity, brain invasion, and presence of other minor criteria. There are numerous histologic variants of meningiomas, and some are associated with worse clinical outcomes and therefore are assigned a higher grade. The majority of meningiomas show diffuse positivity for vimentin and epithelial membrane antigen, supporting the dual mesenchymal and epithelial nature of meningothelial cells. The presence of an elevated proliferation index (as measured by Ki-67 immunohistochemical stain) and loss of progesterone receptor expression are associated with the higher grade. Pathologic features including histologic variants, grading criteria, and ancillary tests such as special and immunohistochemical stains are discussed.

CLINICOPATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES OF 2 CASES OF SOLITARY FIBROUS TUMOR OF THE ORAL CAVITY

Solitary fibrous tumor (SFT) is an uncommon soft tissue tumor that usually occurs in the pleura, but it is extremely rarely in the oral cavity. It presents an extensive microscopic diversity that may turn the diagnosis into a challenge. This is the report of 2 new cases of SFT in the buccal mucosa and tongue highlighting the clinical, microscopic, and immunohistochemical variations. The study included 2 women at 49 and 80 years old. Clinically, they were slow-growing, painless, small, well-defined submucosal masses. Microscopic examination showed well-circumscribed spindle cell proliferations associated with alternating dense hyalinization areas and characteristic stag horn-shaped blood vessels in variable arrangements. Immunohistochemistry showed consistently positivity for CD34 and vimentin, alternating positivity for Bcl-2 and epithelial membrane antigen and negativity for S-100. Patients are well with no recurrence or relapse.

Immunohistochemical Differentiation between Reactive and Malignant Mesothelial Proliferations in Pleural Effusion

AbstractBackground: The differentiation between benign and malignant mesothelial cells in pleural effusion in some cases can be a challenge. In the current study, we investigated the value of immunohistochemistry (IHC) in making that differ-entiation.Aim of Study: This study aims to examine the value of IHC expression of desmin, EMA, GLUT-1, p53, Ki67, and BAP1 in discrimination between benign and malignant mes-othelial proliferation in pleural effusions and compare their results regarding sensitivity and specificity.Material and Methods: Pleural fluids from 30 cases diagnosed as malignant meothelioma (MM) epitheloid type and 20 cases diagnosed as reactive mesothelial hyperplasia (RMH) were selected, and stained with immunohistochemical stains included BAP-1, desmin, epithelial membrane antigen (EMA), glucose-transport protein 1 (GLUTA]1), Ki67, and p53.Results: BAP-1 was negative in 5% (1 of 20) cases of reactive MH and in 63.3% (19 of 30) of MM cases (p 40% of mesothelial cells in 10% (2 of 20) of benign and 16.7% (5 of 30) of malignant cases (p=0.40). EMA negativity and desmin positivity were found in 75% (15 of 20) of reactive MH cases and 3.3% (one of 30) of MM cases. EMA positivity and desmin negativity were found in 5% (1 of 20) of reactive MH cases and 90% (27 of 30) of MM cases (p<.001). Positivity for both of Desmin and BAP-1 was detected in 80% (16 of 20) of RMH cases. The combination of Desmin and BAP-1 negativity was detected in 60% (16 of 30) of MM cases (p-value p<.001).Conclusions: Cases showed positivity for EMA and neg-ativity for desmin strongly favors malignant mesothelioma. On the contrary, cases showed negative EMA and positive desmin strongly favors Reactive mesothelial hyperplasia. also the combination of Desmin and Bap-1 postivity favors diagnosis of RMH, and the combination of Desmin and BAP-1 negativity favors the diagnosis of MM. Similarly, cases showed strong membranous expression of GLUT-1 and/or strong nuclear expression of p53 strongly favors diagnosis of malignant mesothelioma. Proliferative index showed detected by Ki67 showed no significant difference between reactive and malignant cases.

Primary squamous cell carcinoma of the endometrium associated with human papilloma virus in a young woman: a case report

BackgroundPrimary squamous cell carcinoma of the endometrium is an extremely rare tumor with poorly understood pathogenesis.Case presentationWe report a case of a 28-year-old Togolese woman who had consulted for vaginal bleeding and pelvic pain. Ultrasound showed thickening of the lining of the endometrium, and biopsy curettage was done. Anatomopathological examination was noteworthy for a proliferation of squamous cells often connected by union bridges arranged in tumor lobules with dyskeratotic maturation. Immunohistochemistry showed epithelial membrane antigen positivity, anti-pancytokeratin 1 markers of tumor cells positivity, chromogranin A negativity, actin negativity, S100 negativity, estrogen receptor negativity, and progesterone receptor negativity. In situ hybridization had objectified human papillomavirus genotypes 16/18. The diagnosis of primary squamous cell carcinoma of the endometrium associated with human papilloma virus was retained. A hysterectomy was performed, and the tumor was classified pT1N0M0.ConclusionThe pathogenesis of this endometrial cancer is complex, and its association with human papillomavirus does not explain its genesis.

Sinonasal Tract Meningioma

A 63-year old Filipino female presented with epistaxis of undisclosed duration. Examination showed a vascular, pulsating, rubbery intranasal mass involving both nasal cavities. The clinical impression was that of a nasal hemangioma. She underwent excision of the tumor and the specimen was sent for histopathologic evaluation.&#x0D; &#x0D; The specimen consisted of several tan-brown irregular tissue fragments with an aggregate diameter of 2 cm. Microscopic examination showed a cellular spindle cell tumor underneath the respiratory mucosa. (Figure 1) The tumor cells formed a syncytial pattern arranged in whorls that were separated by thin fibrovascular bands. (Figure 2) The cells had round to oval nuclei with nuclear clearing and moderate amount of syncytial cytoplasm compatible with a meningothelial derivation. (Figure 3) There was absence of nuclear atypia, significant mitotic activity, and necrosis. Immunohistochemistry studies showed positivity for Epithelial Membrane Antigen (EMA) and Progesterone Receptors (PR), and absence of reaction for Smooth Muscle Actin (SMA) and CD34. (Figure 4) Our diagnosis was sinonasal tract meningioma.&#x0D; &#x0D; Primary extracranial meningioma of the sinonasal cavity is rare and thus secondary extension from a primary intracranial tumor should be ruled out. It involves a wide age range with no striking gender predilection.1,2 Most common symptoms include nasal obstruction, epistaxis, exophthalmos, and a mass. Etiogenesis is not completely established and is postulated to arise from meningocytes that are entrapped during closure of midline structures, very similar to the development of meningoceles.3&#x0D; &#x0D; Histopathologic examination discloses a spindle cell tumor arranged predominantly in whorls composed of cells showing meningothelial differentiation. Most are histologically grade 1 tumors. Grade 2 and 3 sinonasal tract meningiomas are rare.4 Histologic differential diagnoses include a glomangiopericytoma, leiomyosarcoma, and a solitary fibrous tumor/hemangiopericytoma. Close histologic evaluation with appropriate immunohistochemistry studies point to the correct diagnosis. Meningioma shows strong diffuse positivity with EMA and PR, and is usually negative for other immunohistochemistry markers such as muscle actins (for glomangiopericytoma and leiomyosarcoma), and CD34 (for solitary fibrous tumor/hemangiopericytoma).1,3 A diagnosis of primary sinonasal meningioma should not be made if an intracranial mass is identified.4&#x0D; &#x0D; Sinonasal meningiomas are benign tumors with no documented distant metastases.1,2 Although recurrences occur in about 30% (mostly due to incomplete excision), metastasis and malignant transformation has not been reported.4&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;