Epithelioid Cells Research Articles

Prognosis prediction via histological evaluation of cellular heterogeneity in glioblastoma

Glioblastomas (GBMs) are the most aggressive types of central nervous system tumors. Although certain genomic alterations have been identified as prognostic biomarkers of GBMs, the histomorphological features that predict their prognosis remain elusive. In this study, following an integrative diagnosis of 227 GBMs based on the 2021 World Health Organization classification system, the cases were histologically fractionated by cellular variations and abundance to evaluate the relationship between cellular heterogeneity and prognosis in combination with O-6-methylguanine-DNA methyltransferase gene promoter methylation (mMGMTp) status. GBMs comprised four major cell types: astrocytic, pleomorphic, gemistocytic, and rhabdoid cells. t-distributed stochastic neighbor embedding analysis using the histological abundance of heterogeneous cell types identified two distinct groups with significantly different prognoses. In individual cell component analysis, the abundance of gemistocytes showed a significantly favorable prognosis but confounding to mMGMTp status. Conversely, the abundance of epithelioid cells was correlated with the unfavorable prognosis. Linear model analysis showed the favorable prognostic utility of quantifying gemistocytic and epithelioid cells, independent of mMGMTp. The evaluation of GBM cell histomorphological heterogeneity is more effective for prognosis prediction in combination with mMGMTp analysis, indicating that histomorphological analysis is a practical and useful prognostication tool in an integrative diagnosis of GBMs.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors without an artificial extracellular scaffold. MBM SXOs were created by a novel protocol incorporating techniques for establishing glioma and cutaneous melanoma organoids. A BRAFV600K-mutant and BRAF-wildtype MBM sample were collected directly from the operating room. Organoids were cultured in an optimized culture medium without an artificial extracellular scaffold. Concurrently, matched patient-derived cell lines were created. Organoid growth was observed within 3–4 weeks, and MBM SXOs retained histological features of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, and strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF and MEK inhibitors. Further study using SXOs may improve the translational relevance of preclinical studies and enable the study of the metastatic melanoma tumor microenvironment.

PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that...

MTOR inhibitor in the treatment of TFE-positive advanced maligmnant PEComa of the uterus: a case report and literature review.

The pre- and intra-operative diagnoses of malignant uterine vascular perivascular epithelioid cell tumors (PEComas) can be challenging, for which the literature is limited. Some cases have been shown to have TSC gene mutations or rearrangements of the MiT factor family, resulting in variable responses to mTOR inhibitors. We report a case of a TFE-positive malignant PEComa of the uterus with pulmonary metastases that responded favorably to the mTOR inhibitor, everolimus. A 52-year-old female underwent a total hysterectomy 5 years ago for suspected sub-serosal or broad ligament fibroids. The intraoperative pathologic diagnosis was leiomyosarcoma of the uterus and the postoperative diagnosis was malignant PEComa of the uterus. The patient declined genetic testing and further treatment. In December 2020 the patient presented with a pelvic mass and underwent open abdominal mass resection and pelvic adhesiolysis. The pathologic findings confirmed recurrent malignant PEComa of the uterus. The pulmonary lesions gradually progressed during the follow-up period, so treatment with everolimus was initiated. Close follow-up evaluation for nearly 3 years showed disease remission without recurrence or progression. The patient described herein had a TFE-positive uterine malignant PEComa with lung metastasis and responded well to the mTOR inhibitor, everolimus. Close follow-up in the last 3 years showed remission without recurrence or progression.

Histomorphological features of pulmonary tuberculosis in Asian elephants (Elephas maximus)

Tuberculosis in Asian elephants usually shows involvement of lungs and associated lymph nodes. Grossly, the affected lobes of lungs reveal circumscribed lesions of varying sizes with central areas of caseation and necrosis. This report documents histomorphological features of pulmonary tuberculosis in six Asian elephants. The important cell types present were lymphocytes, foamy macrophages, epithelioid macrophages and Langhan’s type of giant cells. In addition, caseation necrosis, fibrotic capsule, and mineralisation (calcification) were also observed. Characteristic features of tuberculoid granulomas observed in the six cases showed similarities with other species. The six cases showed varying proportions of the seven defined features but all features were present together only in one case Keywords: Granuloma, histopathology

Pseudomyogenic Hemangioendothelioma: A Case Report of a Rare Tumor with Unusual Presentation

Abstract Introduction/Objective Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare neoplasm recently categorized by the World Health Organization (WHO) as an intermediate-grade vascular soft tissue tumor affecting young adults. While most documented cases exhibit local aggressiveness, we present a case with unusual presentation characterized by multiple pelvic and femoral lytic bone lesions associated with documented liver metastases. Methods/Case Report A mid-forties female presented with progressive left hip pain persisting for 2 weeks. Radiological assessments showed multiple lytic lesions in the left superior pubic ramus, right iliac wing, and left greater trochanter with associated pathologic fractures and soft tissue involvement. Additionally, multiple indeterminate hepatic and splenic hypodensities were noted. Histologic examination of the bone and liver biopsies revealed a neoplasm composed of spindled and epithelioid cells with hyperchromatic nuclei and eosinophilic cytoplasm. The neoplastic cells are arranged haphazardly and in short fascicles within a fibromyxoid stroma or sinusoidal spaces (in the liver) associated with scattered acute and chronic inflammation. Frequent mitoses are noted; however, no necrosis was identified. Tumor cells were positive for CD31, ERG, FOSB with equivocal staining for pankeratin and CK8/18. The top differential consideration was epithelioid hemangioendothelioma (EHE); however, sarcoma fusion next-generation sequencing panel exhibited features of a vascular neoplasm with WWTR1-FOSB, favoring PHE. Results (if a Case Study enter NA) NA Conclusion Pseudomyogenic hemangioendothelioma is a rare tumor that is prone for local recurrence and usually affect young adults (mean age: 30 years). Metastases are uncommon. To the best of our knowledge, we report a case of PHE with unusual presentation of early metastases to liver and possibly the spleen and highlights the complexity of PHE diagnosis.

An Anaplastic Lymphoma Kinase (ALK) Immunohistochemical Pitfall: ALK-positive Histiocytosis versus Angiomatoid Fibrous Histiocytoma

Abstract Introduction/Objective The 5th Edition WHO classification expanded the histiocytic/dendritic cell neoplasms to include ALK-positive histiocytosis, which can present as multisystem or single-site disease, affecting various age groups. These tumors lack high-grade cytologic features but express ALK by immunohistochemistry, typically indicating ALK locus rearrangements. In this case study, a cutaneous mass initially suspected as ALK-positive histiocytosis was found to be angiomatoid fibrous histiocytoma (AFH) with ALK expression, highlighting the potential diagnostic pitfall due to overlapping histomorphology and ALK expression. Methods/Case Report A previously healthy twelve-year-old boy sought evaluation for a growing and ulcerating mass on his left arm, which developed gradually over a year post-injury. Laboratory tests showed elevated inflammatory markers and mild anemia. A biopsy of the ulcer revealed Staphylococcus aureus infection. Initial histological examination revealed mixed inflammatory infiltrates with focal necrosis, prominent histiocytes, and giant cells. Despite favoring an infectious cause, immunostains were performed. AE1/AE3, ERG, CD34, CD30, S100, SOX10, SMA, and MyoD1 were negative, while INI1 was retained. However, ALK was strongly positive in some histiocytoid cells, suggesting ALK-positive histiocytosis. Surgical resection was subsequently performed to manage the abscess and characterize the lesion. Histologic examination revealed a solid nodule containing spindled and epithelioid cells with a bland histiocytoid appearance, arranged in a compact syncytial growth pattern within the dermis and subcutis. Surrounding the tumor, there was a distinct cuffing of fibrosis with organized lymphoplasmacytic cells. Break apart fluorescence in situ hybridization studies showed rearrangement of EWSR1 but not ALK. The diagnosis of angiomatoid fibrous histiocytoma was rendered. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of understanding immunohistochemical features, especially those that are unusual and unexpected in rare diseases. With the growing use of minimally invasive sampling techniques, this case study underscores the significance of integrating molecular diagnostics with clinical, histological, and immunophenotypic evaluations to achieve an accurate diagnosis in surgical pathology.

Calcifying Nested Stromal-Epithelial Tumor of the Liver: A Rare Find

Abstract Introduction/Objective Calcifying Nested Stromal-Epithelial Tumor (CNSET) is a rare tumor of the liver with less than 40 cases described in the literature. It is a low-grade tumor characterized by a distinctive nested architecture surrounded by a cellular myofibroblastic stroma and psammomatous calcifications. CTNNB1 gene deletions have been identified in several cases. CNSET typically arises in the right lobe and there is a female predominance with a predilection for children, adolescents, and young adults. Methods/Case Report We report an interesting case of CNSET in a 13-year-old male with no pertinent medical history who presented with a one-month history of fatigue, paleness, and liver mass on physical examination. MRI abdomen showed a 9.8 cm heterogenous mass with a central scar involving the right lobe of the liver, radiologically favored to be fibrolamellar hepatocellular carcinoma. AFP levels were normal. The patient underwent a partial hepatectomy. On gross examination, the specimen showed a yellow, circumscribed, firm mass. H&E slides showed scattered round to oval nests of bland spindle and epithelioid cells arranged in short fascicles at the periphery of nests. Collagenous stroma surrounding the nests showed spindle cells with tapered nuclei and pinpoint nucleolus. Areas with calcification and osseous metaplasia were also present. Immunohistochemistry performed showed the tumor cells to be positive for pan-cytokeratin (weak), WT-1, and vimentin, and negative for Hepar-1, arginase-1, synaptophysin, chromogranin, S100, NUT-1, myogenin, and desmin. Beta-catenin showed nuclear and cytoplasmic staining pattern. INI-1 was retained within the tumor cells and Ki-67 showed a proliferative index of approximately 10-20%. On MSK-Impact (next- generation sequencing), a mutation in CTNNB1 was detected. Archer FusionPlex was negative for gene fusions within the tumor. Results (if a Case Study enter NA) NA Conclusion It is crucial to become familiar with this rare entity and to avoid mistaking it for hepatoblastoma. CNSET exhibits a biphasic morphology characterized by a nested architecture featuring bland and uniform epithelioid and spindle cells, surrounded by a cellular myofibroblastic stroma. Confirming the diagnosis can be aided by nuclear β- catenin and the expression of WT1.

Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444

Abstract Introduction/Objective Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma. Methods/Case Report A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months. Results (if a Case Study enter NA) NA Conclusion Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.

Cardiac Angiosarcoma with Unusual Cytologic Features Causing Cardiac Tamponade in a Young Adult Patient

Abstract Introduction/Objective Cardiac angiosarcoma is a rare endothelial malignancy with poor prognosis, frequent metastasis, and short median survival of only a few months. The disease has a wide age spectrum and can occur in young adult patients. The cytological diagnosis of cardiac angiosarcomas is challenging as cases are rare and its cytology is not extensively described or reported in literature. Here, we describe a rare case of cardiac angiosarcoma with unusual cytologic features. Methods/Case Report Our patient is a 30 year old male presenting with three days of worsening dyspnea and palpitations and was discovered on ultrasound to have large pericardial effusion compressing the right ventricle and causing cardiac tamponade. CT/MRI imaging revealed a 4.5 x 4.3 x 2.6 cm mass inside the right ventricle with extra- cardiac invasion through the pericardium and into the anterior mediastinum. Pericardiocentesis yielded 1.5 liters of hemorrhagic, brown, pericardial fluid with elevated LDH and protein levels. Cytology of the pericardial fluid revealed numerous tumor cells occurring singly or in monolayered, acinar clusters or cohesive spheres containing amorphous, eosinophilic cores made of collagen as evidenced on trichrome stain. The tumor cells possessed hyperchromatic, irregular, variably sized nuclei, prominent nucleoli, and cytoplasmic vacuoles. The tumor cells were positive for vimentin, CD31, and CD34, and showed high Ki67 proliferation index > 50%. A catheter-mediated biopsy of the right ventricular mass revealed spindled and epithelioid tumor cells strongly positive for CD31, CD34, and vimentin, focally positive for Factor VIII and AE1/AE3, and showing high Ki67 proliferation index of roughly 50%. The cytological, histological, and immunohistochemical findings were most consistent with cardiac angiosarcoma as the diagnosis. The patient eventually developed worsening chronic left chest pain and expired from cardiac arrest six months after his diagnosis. Results (if a Case Study enter NA) NA Conclusion We report a rare case of cardiac angiosarcoma with unusual cytologic features, manifesting as acinar clusters and cohesive spheres with collagenous cores that are not typical of malignant endothelial neoplasms. Currently there are no effective, standardized therapies that can significantly prolong survival for this malignancy, and treatment is often palliative. The cytological diagnosis of cardiac angiosarcoma is challenging given the rarity of this disease and the paucity of literature describing its cytology.

Pseudolipoblastic Perineuroma: A Rare Histologi̇c Subtype.

Pseudolipoblastic perineurioma is a very uncommon variant of extraneural perineurioma, with only a limited number of cases documented in the medical literature. The most remarkable histopathologic characteristic is the existence of vacuolated cells that closely resemble lipoblasts; besides the presence of small, spindle shaped, or epithelioid perineurial cells. In this study, we present another case of pseudolipoblastic perineurioma, predominantly characterized by the presence of vacuolated "pseudolipoblastic" cells. The immunohistochemical expression of EMA, Glut-1, claudin-1, collagen type IV, and laminin as well as S-100 negativity is essential for the diagnosis to support the perineurial origin. Simple excision is the best treatment option for these benign tumors that do not recur or metastasize. It is crucial to recognize this rare entity to differentiate it from many other tumors characterized by prominent intracytoplasmic vacuoles.

Anaplastic transformation of papillary thyroid carcinoma in the cervical lymph nodes showing a variety of rhabdoid, epithelioid and spindle cell phenotype

Abstract Introduction/Objective Anaplastic thyroid carcinoma (ATC) is a rare undifferentiated tumor of thyroid follicular cells with a dismal prognosis. Most ATCs derive from pre-existing, well-differentiated thyroid carcinomas, most commonly papillary thyroid carcinoma (PTC). In nearly all instances, ATC arises within the thyroid gland. Completely divergent morphologies of this tumor between the bilateral cervical nodes as well as the almost exclusive presence of ATC in the metastatic and nodal locations are very unusual and are reported here. Methods/Case Report A 67-year-old man presented with a rapidly enlarging left cervical mass, hoarseness, dry cough, and drooping left eye. MRI demonstrated bilateral enlarged cervical lymph nodes spanning levels II to V, and nodules in thyroid lobes. Subsequent total thyroidectomy with bilateral radical neck dissection was performed. Histologically, the left lateral cervical masses revealed undifferentiated tumor cells with rhabdoid, epithelioid and spindle cells features. Conversely, the tumor within the thyroid lobes and the right cervical lymph nodes exhibited PTC with tall cell features. All undifferentiated tumor components stained positive with AE1-3, CK7, PAX8, and negative with thyroglobulin, EMA, CD34, S100, Melan-A, Sox 10, desmin, myogenin, and P40. INI-1 staining is retained. Only the spindle cell component stained positive with TTF1. Based on the morphology and immunoprofile, a diagnosis of anaplastic thyroid carcinoma was rendred. Results (if a Case Study enter NA) NA Conclusion Diagnosing anaplastic thyroid carcinoma outside the thyroid lesion can be challenging. In our case, only extensive sampling of the surgical specimen identified a small focus of well-differentiated PTC, staining positive for thyroglobulin, in the left cervical anaplastic carcinoma component, identifying its origin. This case adds to the scarce literature documenting unilateral anaplastic transformation in the left cervical metastatic lymph nodes, while the right cervical lymph nodes contained pure well differentiated PTC. This represents a significant potential pitfall in presurgical fine needle aspiration (FNA) evaluation of patients with ATC.

Malakoplakia, a rare inflammatory condition presenting as a colon polyp

Abstract Introduction/Objective Malakoplakia is a rare histiocytic disease caused by defects in phagocytic or degradative functions of histiocytes in response to gram negative coliforms (E. coli or Proteus) that results in chronic inflammatory state, followed by intracellular deposition of iron and calcium (known as Michaelis-Gutmann bodies). It’s more common in immunocompromised patients and the mean age at diagnosis is fifth decade. It occurs in all organs, common in GU tract, particularly bladder, but also seen in gastrointestinal tract (most commonly colon, followed by stomach and duodenum), central nervous system and female genital tract. In gastrointestinal tract, it can present as a polyp with diffuse mucosal involvement, submucosal thickening, and even may cause mass. Methods/Case Report A 60 -year-old male smoker presented to our hospital with history of colon polyps; colonoscopy revealed a 6 mm sessile polyp at the hepatic flexure. A biopsy was performed which showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, abundant Michaelis-Gutmann bodies and increased lymphocytes. Immunohistochemical stains showed diffuse positivity for CD68; and PAS stain was positive for histiocytic cytoplasmic granules. Based on this data, the diagnosis of Malakoplakia was confirmed. Malakoplakia is treated with antibiotics that concentrate in macrophages (quinolones or trimethoprim-sulfamethoxazole), antibiotics directed against E. coli, surgery and possibly discontinuation of immunosuppressive drug therapy. Results (if a Case Study enter NA) Malakoplakia, in this case, was presented clinically as a sessile colon polyp and histologically showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, with Immunohistochemical stains (CD68; and PAS stain) the correct diagnosis was made. Other presentations of Malakoplakia include diffuse mucosal involvement, submucosal thickening, or mass. Histologically, it may rarely be mistaken as signet ring carcinoma. These variable presentations in GU tract or colon can be interpreted as malignancy with consequent unnecessary interventions. Hence, awareness of Malakoplakia with careful histopathologic examination and the use of immunohistochemical studies are advisable in that cases. Conclusion We would like to emphasize that Malakoplakia can be clinically and histologically misdiagnosed as a malignant condition; therefore histopathologic and immunohistochemical studies are needed to correctly diagnose this entity.

Multisystem ALK-Positive Histiocytosis With DCTN1::ALKFusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

Dual infection of maxillary sinus masquerading as a malignant lesion; A rare presentation

Primary sinonasal tuberculosis is a rare form of TB even in developing countries where TB is prevalent and invasive mycotic infection is more common in immunocompromised patients. It is unusual to have a dual infection with tuberculosis and mycosis in the maxillary region mimicking a neoplastic process and causing bone erosion. A 49-year old male presented with 2-year history of left-sided facial swelling. On microscopic examination, epithelioid cell granulomas, chronic inflammatory infiltrate, macrophages, giant cells, and focal necrosis were seen. Ziehl Neelsen staining for acid-fast bacilli with 20% H2SO4 was positive. Fungal hyphae were also seen in the sections examined. Special stains (Periodic acid-Schiff and Grocott’s methenamine silver stain) for fungal hyphae were positive. Mycosis and tuberculosis should always be considered in the differential diagnosis of maxillary lesions or sinusitis.

Syringocystadenoma Papilliferum-Like Features in Poroma: An Unusual Morphologic Pattern of Poroma or True Synchronous Occurrence of 2 Distinct Neoplasms?

Poromas are benign adnexal neoplasms of eccrine origin, believed to arise from the outer layer of acrosyringia and upper dermal eccrine ducts, with a predilection for glabrous skin. They typically present as a pink or red papule with a surrounding thin moat on the palms and soles. We report a case of poroma with histopathologic features reminiscent of syringocystadenoma papilliferum (SCAP). A 70-year-old woman presented with a 2.0 cm pedunculated nodule on the left suprapubic abdomen. Histopathologically, the lesion predominantly displayed features of a conventional poroma but also included areas with endophytic invaginations lined by large, plump epithelioid cells with abundant eosinophilic cytoplasm and occasional decapitation secretion, alongside a stroma rich in plasma cells-characteristics suggestive of SCAP. However, definitive bilayers with myoepithelial cells were not observed. Immunohistochemical studies revealed that the tumor cells were positive for TRPS1 (particularly around SCAP-like areas) and CEA (indicating ductal differentiation), but negative for BRAF V600E and NUT. The diagnosis of poroma with apocrine differentiation mimicking SCAP was favored. This unusual morphologic variation in poromas is rare, with fewer than 5 cases documented in the literature. These SCAP-like features likely represent a variation within the morphologic spectrum of poromas rather than the presence of 2 synchronous tumors. Our case highlights the importance of recognizing such variations in poroid neoplasms to ensure accurate diagnosis.

Diffuse meningeal melanocytosis – a silent culprit

Abstract Introduction/Objective Diffuse meningeal melanocytosis is a rare melanocytic proliferation that poses significant risk of severe hydrocephalus and mortality among children and young adults. Although the clonal melanocytes do not typically exhibit malignant morphological features, their capability for extensive invasion and malignant-like behavior necessitates tissue biopsy alongside immunohistochemical and molecular testing for definitive diagnosis. Methods/Case Report A 17-year-old male presented with progressive headaches, photophobia, and nausea, initially attributed to migraines. Neuro-opthalmological assessment revealed papilledema, leading to a diagnosis of idiopathic intracranial hypertension. Serial imaging showed fluctuating leptomeningeal enhancement and moderate communicating hydrocephalus without parenchymal lesions. Therapeutic lumbar punctures provided modest symptom improvement; increased opening pressure was observed. Evaluation of seven CSF specimens showed low glucose levels, increased cellularity consisting of bland appearing epithelioid cells of unknown etiology, and increased lymphocytes. Infectious causes were excluded. Due to the indeterminate CSF findings, discussion between the cytopathologist and neuro-opthamologist was crucial to facilitate tissue biopsy to exclude a neoplastic process. Subsequent shunt placement and cerebral cortex biopsy revealed neoplastic cells with sheet-like architecture coating the dura without overt brain invasion. The tumor cells had eosinophilic cytoplasm without pigment and enlarged nuclei with irregular contours, vesicular chromatin, and prominent nucleoli. No high-grade features were seen. Immunohistochemical stains were positive for MART1, HMB45, and PRAME, consistent with a melanocytic lesion. FISH melanoma panel was negative. The final diagnosis was diffuse meningeal melanocytic neoplasm, most consistent with meningeal melanocytosis. The patient received chemotherapy with improved symptoms and stable disease. Results (if a Case Study enter NA) NA Conclusion Diffuse meningeal melanocytosis is a challenging cytologic diagnosis as melanocytes can morphologically mimic lymphocytes and monocytes, and the low cellularity of CSF specimens often results in insufficient cell blocks for ancillary tests. The direct communication of the pathologist with the clinical team to correlate pathology, radiology, and clinical symptoms was essential to ensure the proper management of this patient.

Gastrointestinal Stromal Tumor (GIST) masquerading as undifferentiated gastric carcinoma; a potential diagnostic pitfall

Abstract Introduction/Objective Epithelioid variant of the GIST can mimic carcinoma and misdiagnosis has grave implications in patient management. The purpose of this report is to describe such a case and to remind pathologists to keep epithelioid GIST in the differential. Methods/Case Report A 66-year-old male presented with melena for 2 weeks. Endoscopy showed a large, infiltrative, and ulcerated mass in the gastric fundus. CT imaging showed a 16 x 12 cm mass-like gastric wall thickening, most compatible with gastric carcinoma. The mass was biopsied, which showed sheets and clusters of anaplastic, large to medium sized polygonal epithelioid cells with areas of rhabdoid phenotype characteristic of an undifferentiated gastric carcinoma. Initial immunohistochemical stains including pancytokeratin and p40 showed negativity, prompting additional stains including Cam5.2, SOX10, CD45, synaptophysin, INSM1, EMA, CK7 and CK20- all of which were also negative. At this point the main diagnostic consideration was undifferentiated gastric carcinoma. However, for completion purposes, DOG1 stain was added that came back positive. Since rhabdoid morphology is a bit unusual, even for epithelioid GISTs, and literature review suggested that DOG1 positivity can be seen in up to 11% of carcinomas, confirmatory NGS testing was performed. This demonstrated a KIT W557R gene mutation, confirming the diagnosis of GIST. The patient was treated with imatinib and subsequent imaging showed decreased size and hypermetabolism of the gastric mass. Patient is alive with disease 6 months after the diagnosis. Results (if a Case Study enter NA) NA Conclusion Using a panel of appropriate immunohistochemical stains and keeping epithelioid GIST in the differential can help avoid this diagnostic pitfall.

EVERY KERATIN-POSITIVE MALIGNANT TUMOR IN THE ADRENAL GLAND IS NOT METASTATIC CARCINOMA- A CASE REPORT

Abstract Introduction/Objective Angiosarcoma is a rare subtype of sarcoma arising from the vascular endothelial cells. Primary adrenal angiosarcoma (PAA) is an exceedingly rare entity, with only 53 cases documented in the literature so far. Methods/Case Report A 78-year-old female presented with left upper quadrant abdominal pain and early satiety. A computed tomography scan of the abdomen revealed a 15 x 13 x 16 cm, heterogeneous enhancing mass with interspersed calcifications, possibly originating from the left adrenal gland. The mass was found to be displacing the spleen and the left kidney. An ultrasound-guided biopsy of the mass was inconclusive, and the patient subsequently underwent resection of the left retroperitoneal mass, left adrenalectomy, splenectomy, and left partial nephrectomy. Gross examination revealed a slightly ruptured, red-brown mass (19.5 x 12.7 x 12.6 cm, 1784g), which was serially sectioned to reveal diffusely hemorrhagic and necrotic cut surfaces. On microscopic examination, the tumor was almost entirely hemorrhagic and necrotic, with a few viable areas that were composed of solid sheets of markedly pleomorphic epithelioid cells with a high nuclear-cytoplasmic ratio, prominent nucleoli, and increased mitotic figures. There were also a few ectatic vascular spaces lined by these markedly pleomorphic epithelioid cells. Immunohistochemical stains of the tumor cells showed positive results for cytokeratins, CD31, ERG, and friend leukemic integration 1 (FLI-1), while Inhibin and SF-1 were negative. A diagnosis of epithelioid angiosarcoma was rendered. Results (if a Case Study enter NA) NA Conclusion PAA can be difficult to diagnose since it is rare, and thus it is not typically considered in the initial differential diagnosis. Most PAA have an epithelioid morphology, and they frequently test positive for cytokeratins. Biopsy diagnosis can also be challenging, as the mass may exhibit extensive necrosis and hemorrhage. Considering its rarity, large adrenal masses with heterogeneous features on imaging PAA should be considered as a differential diagnosis.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Fifteen lesions (3-42mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AML contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four AL contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.