Characterization of A Rare Case of Vulvar Epithelioid Sarcoma with local recurrence and metastases

Introduction/Objective Epithelioid sarcoma (ES) is a rare, malignant mesenchymal neoplasm that has a known tendency for local recurrence, regional lymph node involvement, and distant metastases. Two histologic variants have been recognized: classic ES also known as the distal type, and proximal-type ES (PES). The classic ES is common in young adults. It occurs more frequently in the distal upper extremities followed by the distal lower limbs and has a male prevalence of 2:1. Conversely, PES commonly involves deep tissues in the pelvic region, including the genital area. It tends to occur in older patients and follows a more aggressive clinical course. In the female genital tract, PES occurs most frequently in the vulva. The incidence of primary sarcoma of the vulva accounts for 1.5-5% of all malignant tumors, making PES a very rare incidence. Methods/Case Report Here we report a 60-year-old female diagnosed with vulvar epithelioid sarcoma treated with a right radical vulvectomy and bilateral inguinal lymph node dissection in 2008. In 2017, further surgery and adjuvant radiation were given for local recurrence. In 2020, the patient developed left hip pain and was found to have an expansile lytic lesion in the left proximal femur. Extensive resection was performed. Grossly the vulvar lesion was nodular with diffuse hemorrhage, degeneration, and necrosis. Microscopically, the tumor cells had large vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Histologically, the morphology of the tumor cells are similar for the primary vulvar specimen and the bone metastases. Immunohistochemically, the tumor cells are positive for vimentin, GATA, FLI-1, SMA, SMHC, partially positive for CAM5.2, AE1/AE3, CD31, and CD163. Immunohistochemistry was negative for CDX2, CD56, S-100, TTF-1, CK5/6, CK20, P40, mammoglobin, MOC31, ER, CK7, CK903, HMB45, PAX8. A Ki-67 proliferative index was around 30-40%. NGS molecular testing detected a SMARCB1 mutation with loss of exons 1-3 and exons 7-9 supporting the diagnosis of epithelioid sarcoma. Results (if a Case Study enter NA) NA Conclusion In summary, we report a case of PES of the vulva in a 60 year old female. Grossly, the lesion was nodular with histology showing large vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. It showed loss of INI1/SMARCB1 nuclear expression. The patient is receiving further adjuvant treatment and shows no new metastases.

Histopathological study of canine hepatoid gland tumours

Hepatoid gland neoplasms arise due to disorganized and uncontrolled proliferation of cells of hepatoid glands. These are the modified sebaceous glands located mainly in the perianal area. Gross and histological findings of canine hepatoid gland tumours were evaluated. Dogs of different breed, age and sex that were presented to Department of Veterinary Surgery and Radiology, College of Veterinary and Animal Sciences, Mannuthy formed the materials for the present study. Grossly, tumours were solitary or multiple irregular shaped intradermal masses. The excisional biopsy samples were collected in 10 per cent neutral buffered formalin after surgical removal of tumour mass. Histopathologically, the masses were encircled by fibrovascular capsule which extended to the parenchyma as tumour stroma, which separated it into lobules. Two cases of hepatoid gland adenoma one case of hepatoid gland epithelioma and two cases of carcinoma were recognised on histopathological examination. Hepatoid adenoma were characterised by proliferation of hepatocyte like hepatoid gland epithelial cells with extensive sebaceous differentiation and were arranged in cords and anastomosing trabeculae. In hepatoid gland epithelioma, many of the cells were basaloid reserve cells with fewer hepatocyte like cells. Histopathological examination of carcinoma revealed irregular arrangement of the hepatoid cells which showed varying degrees of maturation and marked nuclear pleomorphism. The malignant hepatoid cells had abundant eosinophilic cytoplasm and large nuclei with several prominent nucleoli and mitotic figures.

Low-Grade Fumarate Hydratase-Deficient Renal Cell Carcinoma in a 30-Year-Old Female

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and clinically aggressive RCC subtype that is commonly associated with the hereditary leiomyomatosis and renal cell carcinoma syndrome. The diagnostic hallmark of FH-deficient RCC is a high-grade microscopic appearance with prominent inclusion-like eosinophilic nucleoli and perinucleolar halos. Herein we report a case of an FH-deficient RCC in a 30-year-old female that exhibited low-grade nuclei and abundant eosinophilic cytoplasm, reminiscent of the clinically more indolent succinate dehydrogenase-deficient RCC subtype and the newly described eintity, eosinophilic, solid and cystic RCC. This case illustrates that FH-deficient RCC can have a wide spectrum of microscopic appearances, including low-grade eosinophilic RCC. In addition, it highlights that a low threshold to perform the immunohistochemical stains for FH and S-(2-succino) cysteine is warranted in RCC cases with unusual and even low-grade eosinophilic morphology.

Mucinous Cystadenoma of the Ovary Associated with Hyperplasia of Stromal Leydig Cells in Pregnant Woman

Background: The hormonally induced non-neoplastic lesions of ovarian stroma during pregnancy must be recognized by pathologist in order to avoid mistaking them for true tumors. Case report: A 28-year-old woman was delivered of a healthy infant by cesarean section. As an incidental finding, a multicystic tumor in the left ovary was found and resected. Histopathology was consistent with benign mucinous cystadenoma. In addition, within the stroma beneath the lining mucinous epithelium, a dense population of cohesive polygonal cells with abundant eosinophilic cytoplasm, typically resembling the Leydig cells, was seen. They were uniform without atypia, accompaning by minimal proliferative activity. They strongly expressed vimentin, inhibin, CD99 and calretinin. The final diagnosis of mucinous cystadenoma associated with hyperplasia of stromal Leydig cells was made. Conclusions: Leydig cell hyperplasia belongs to the specific changes of ovarian stroma associated with pregnancy. The present case stresses that in such situation the pathologists should be aware of it and not confuse it with a tumor.

An Update on Molecular Genetic Aberrations in Spitz Melanocytic Proliferations: Correlation with Morphological Features and Biological Behavior

<p>The aim of the paper is to give an update on molecular genetic aberrations in Spitz melanocytic proliferations with special em- phasis on their correlation with morphological features and biological behavior. The Spitz group of melanocytic proliferations is defined by a combination of distinctive morphological features and driver molecular genetic events. Morphologically, these neoplasms are characterized by large, oval, polygonal, or spindled melanocytes with abundant eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, often in association with epidermal hyperplasia. Molecular aberrations in Spitz melanocytic proliferations can be divided into two main groups, according to the driver genetic change: 1) 11p amplification/HRAS muta- tion, present in about 20% of cases, and 2) kinase fusions, present in about 50%, further subdivided into tyrosine kinase fusions (ALK, ROS1, NTRK1, NTRK3, MET, RET) or serine-threonine kinase fusions (MAP3K8, BRAF). Driver genetic aberrations can be detected along the whole biological spectrum of Spitz melanocytic proliferations, and are mutually exclusive. Although driver genetic aberrations enable proliferation of melanocytes, additional genetic events (often biallelic inactivation of CDKN2A and TERT promoter mutations) are necessary for the development of overt Spitz malignancy.</p><p><strong>Conclusions</strong>. Recent studies have demonstrated that certain driver genetic aberrations are more often associated with the benign spectrum of Spitz melanocytic proliferations and indolent biological behavior (11p amplification/HRAS mutation, tyrosine kinase fusions). In contrast, some driver aberrations are more frequent in the atypical/malignant spectrum of Spitz melanocytic proliferations with a potential for aggressive biological behavior (serine-threonine kinase fusions). In addition, certain driver aberrations are often associated with distinctive morphological features. However, none of the morphological features is entirely specific for any of these driver genetic aberrations. Immunohistochemistry for ALK, ROS1, and pan-TRK can be used for screening purposes to detect cor- responding fusion proteins.</p>

Oncocytic Change in Thyroid Pathology

Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been called Hürthle cells but this is a misnomer, since Hürthle described C cells; for this reason, we propose the use of “oncocyte” as a scientific term rather than an incorrect eponym. Oncocytic change occurs in nontumorous thyroid disorders, in benign and malignant tumors of thyroid follicular cells, in tumors composed of thyroid C cells, and intrathyroidal parathyroid proliferations as well as in metastatic lesions. The morphology of primary oncocytic thyroid tumors is similar to that of their non-oncocytic counterparts but also is complicated by the cytologic features of these cells that include both abundant eosinophilic cytoplasm and large cherry red nucleoli. The molecular alterations in oncocytic thyroid tumors echo those of their non-oncocytic counterparts but in addition feature mitochondrial DNA mutations as well as chromosomal gains and losses. In this review we emphasize the importance of recognition of the spectrum of oncocytic thyroid pathology. The cell of origin, morphologic features including architecture, nuclear atypia and invasive growth, as well as high grade features such as mitoses and necrosis, enable accurate classification of these lesions. The molecular alterations underlying the pathological entity are associated with genetic alterations associated with oncocytic change. The arbitrary cut-off of 75% oncocytic change to classify a lesion as an oncocytic variant brings another complexity to the classification scheme of tumors that frequently have mixed oncocytic and non-oncocytic components. This controversial and often confusing area of thyroid pathology requires thoughtful and cautious investigation to clarify accurate diagnosis, prognosis and prediction for patients with oncocytic thyroid lesions.

Histiocytic Sarcoma Arising From a Long Bone: Report of Two Cases

Histiocytic sarcoma is a rare, but aggressive malignant neoplasm of monocyte/macrophage lineage with a wide age distribution. Bone involvement is exceedingly rarer compared to the lymph node, skin, and soft tissue, and no long bone involvement has been reported in the English literature. We here report 2 cases of histiocytic sarcoma involving the long bone: one from the femur of a 77-year-old female, status post the placement of an intramedullary nail for subtrochanteric hip fracture; the other from the radius of a 3-year-old female with no significant medical history. Radiologic imaging showed highly destructive lesions in both cases with soft-tissue extension. Microscopy in both cases showed sheets of polygonal mononuclear cells with abundant eosinophilic cytoplasm, prominent nucleoli, and frequent mitosis. Hemophagocytosis were also identified. Immunohistochemistry showed that the lesional cells were strongly diffusely positive for CD68 and CD163. The first patient deteriorated rapidly, despite the aggressive treatment of amputation and chemotherapy. However, the second patient is disease free 36 months post the treatment of amputation only. We conclude that the long bone could be the primary site of histiocytic sarcoma. Its prognosis could be very variable and it is difficult to predict its behavior based on morphological evaluation only.

Tall Cell Variant of Papillary Thyroid Carcinoma: Recognizing a Rare Aggressive Variant

Papillary Thyroid Cancer (PTC) accounts for 80–90% of all thyroid malignancies [1]. The most common morphology is the classical papillary which has an indolent course. Aggressive variants exist, of which Tall Cell Variant (TCV) is the most common. TCV is defined as a PTC in which 30% or more of tumor cells are 2-3 times as long as they are wide [1,2]. The histology image (Figure 1A, magnification 4x) shows tumor cells arranged back to back with abundant eosinophilic cytoplasm, and typical nuclear features of PTC; namely overlapping enlarged nuclei, intranuclear grooves, and occasional pseudoinclusions. Figure 1B (magnification: 20x) shows a high power view of the same case where the tall cell features of individual tumor cells can be better appreciated (arrows). This important feature should be recognized and reported in pathology reports as TCVs exhibit worse clinical course with extensive lymph node metastasis, extra thyroidal extension and high rate of recurrence [1,2].

Malignant Phyllodes Tumour with Rhabdomyosarcomatous Differentiation: A Rare Phenomenon

Phyllodes tumour is a rare tumour of the breast constituting less than 1% of all breast tumours. Malignant Phyllodes Tumour (MPT) accounts for only 10-30% of all phyllodes tumours. Heterologous sarcomatous differentiation in a MPT is an infrequent phenomenon, with the cases reported showing differentiation mostly towards liposarcoma, fibrosarcoma, angiosarcoma, osteosarcoma, or chondrosarcoma. MPTs with rhabdomyosarcomatous differentiation are scarcely seen with only three confirmed cases documented till date to the best of the knowledge after a thorough search of literature. Here, authors present a case of 45-year-old female who presented with a well-defined rapidly growing lump in the right breast for last one year. A core needle biopsy performed showed a sarcomatous picture on histology. Complete excision was subsequently done. On microscopy, most of the areas showed fibrosarcomatous changes with frequent mitoses. Some of the foci showed large pleomorphic cells in diffuse sheets that were polygonal with densely abundant eosinophilic cytoplasm and vesicular nucleus with prominent nucleoli (rhabdomyoblasts). Myogenin was diffusely positive on Immunohistochemistry (IHC). A diagnosis of MPT with rhabdomyosarcomatous differentiation was made. This case is reported here for its unusual presentation and to make pathologists aware of this rare heterologous differentiation of MPT.

A rare and overlooked cause of massive gastrointestinal bleeding: Distal duodenal GIST

Introduction. Gastrointestinal stromal tumors (GIST) are tumors of mesenchymal origin which originate from the walls of gastrointestinal system (GIS) organs. Aim. In this case report we aim to discuss the clinical, labaratory and radiological presentation of distal duodenal GIST as a rare and overlooked cause of life-threatining GIS bleeding. Description of the case. A 76-year-old male patient was presented to the emergency department with massive gastrointestinal bleeding. Computerized tomography revealed a mass soft tissue density of 4x4cm at the level of the 3-4th segment of the duodenum. At the endoscopy, there was a deep ulcer in the proximal part of the 3rd segment of the duodenum with a diameter of 2 cm with a bleeding vessel protruding into the lumen. After endoscopic treatments, biopsies were taken from the edges of the ulcer. Histopathological examination revealed a sheet-like infiltration composed of mildly pleomorphic cells with oval-spindle nuclei and abundant eosinophilic cytoplasm in the duodenal lamina propria, as the patient was diagnosed of GIST. Conclusion. GIST and its clinical, labaratory and radiological presentation should be kept in mind in the approach to massive duodenal GIS bleeding.