Pleomorphic Nuclei Research Articles

SPREADING OF GLANDULAR MALIGNANCY MIMICKING BONE LESION: REPORT OF TWO CASES

Peripheral nerves are target for local invasion and spreading in pancreatic, gastric, prostate, and head and neck cancers. Adenoid cystic carcinoma (ACC) accounts less than 10% of salivary gland neoplasms with dual cell population, typically exhibiting three architectural patterns. Distant metastasis and neural involvement are common clinical features. Objectives To report two rare cases of ACC arising from parotid gland and extending into mandible through mandibular foramen. Results A 50-year-old woman and 49-year-old man presented with pain and parestesia in the left face. A swelling was observed and computed tomography detected osteolytic lesion with irregular margins involving complete body and ramus in the left side of the mandible. Clinical diagnosis was established of osteomyelitis and sarcoma. Microscopically, both tumors presented as solid masses with few ductiform structures. Tumor cells had basaloid appearance with large pleomorphic and prominent nuclei or densely hyperchromatic with scant cytoplasm. Frequent mitotic figures and comedolike necrosis were seen. Tumor infiltration was detected in the perineurial region of the inferior alveolar nerve and within bone medula. In one case, tumor cells has spread to the dental pulp. Immunohistochemically, tumor cells in one case were positive for CK7, 34BE1, CD117, Ki67 (>5 in 10hpf) and negative for p63 and CK5/6. Conclusion Two rare cases of mandibular extension of a parotid gland ACC through the mandibular foramen is presented. Computed tomography and magnetic resonance confirmed primary ACC in the parotid gland, suggesting access of tumor cells through mandibular canal. Meticulous clinical and radiographic analysis were essential to detect primary tumor for an appropriate therapy.

HEPATOPROTECTIVE ACTIVITY OF CORDIA OBLIQUA AGAINST PARACETAMOL-INDUCED LIVER TOXICITY ON WISTAR RATS

Objective: The ethanolic extract of Cordia obliqua (EECO) Willd. leaves was evaluated for hepatoprotective activity in Wistar rats by inducing hepatic damage with paracetamol.
 Methods: The leaves of C. obliqua were dried under shade, segregated, pulverized by a mechanical grinder and passed through a 40 mesh sieve. The powdered plant materials were stored in an air-tight container. The above-powdered materials were successively extracted with ethanol by hot continuous percolation method in Soxhlet apparatus for 24 h. The extract was concentrated using a rotary evaporator and subjected to freeze drying in a lyophilizer till dry powder was obtained.
 Results: Treatment with EECO at 200 and 400 mg/kg showed significant decrease in serum glutamate-pyruvate transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, and total bilirubin levels and a significant elevation in the total protein, albumin, and globulin levels in serum when compared with paracetamol treated rats. In histological study of liver, the hepatocytes show moderate cytoplasm and moderately enlarged pleomorphic and hyperchromatic nuclei. The portal triads show mild periportal inflammation composed of lymphocytes, and central veins are normal.
 Conclusion: On the basis of results, we can conclude that the EECO leaves showed potential hepatoprotective activity in rats.

Hexavalent chromium-induced toxic effects on the antioxidant levels, histopathological alterations and expression of Nrf2 and MT2 genes in the branchial tissue of Ctenopharyngodon idellus

Ability of hexavalent chromium to accumulate and induce oxidative stress has been studied in the gills of Ctenopharyngodon idellus, with the resulting damage in the form of altered endogenous antioxidant enzyme activity and, histopathology in the tissue. The fish were exposed to 5.3 (C1) and 10.63 mg/L (C2) of hexavalent chromium and were scrutinised on 15th, 30th and 45th day of toxicant exposure. Oxidative stress studied in terms of lipid peroxidation and glutathione levels and the antioxidant enzymes activity also exhibited alterations. The histopathological modifications in gills announced lesions in the form of hyperplasia, aneurysm, lamellar fusion, focal proliferation, epithelial degeneration and necrosis with loss of lamellae, bringing irreversible damage on 45th day with mean degree of tissue change value of 100.35 ± 10.69. Bioaccumulation of chromium, and increased anomalies in branchial tissue exhibited damage in concentration and time-dependent manner. The ultrastructural anomalies in the cellular morphology in the epithelial cells of filaments and lamellae, exhibited pleomorphic nuclei, swollen mitochondria, extensive vacuolation and loss of microridges in pavement cells. The tissue also displayed altered regulation of Nrf2 and Mt2 following Cr(VI) exposure with maximum downregulation on 45th day by 61 and 53%, respectively. PCA generated two principal components, PC1 (GSH, GST, CAT and SOD) and PC2 (DTC, MDA and Cr(VI) concentration). Thus, it can be concluded that accumulation of Cr(VI) induces alteration in the gene expression of Nrf2 and Mt2 leading to the development of oxidative stress, ensuing various pathological changes creating hindrance in fish survival.

Pleomorphic LCIS what do we know? A UK multicenter audit of pleomorphic lobular carcinoma in situ

Background: Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively newly described pathological lesion that is distinguished from classical LCIS (cLCIS) by its large pleomorphic nuclei. The lesion is uncommon and its appropriate management has been debated. The aim of this study is to review data from a large series of PLCIS to examine its natural history in order to guide management plans.

Clear Cell Myoepithelial Carcinoma Arising from the Hard Palate with Metastasis to the Lungs

Myoepithelial carcinoma is an uncommon tumor of the salivary glands, most commonly the parotid gland. Clear cell myoepithelial carcinoma is a rare variant with an aggressive behavior. Here, we describe a case of clear cell myoepithelial carcinoma arising from the hard palate in an elderly male who underwent resection of the tumor and postop radiation. Posttreatment imaging demonstrated bilateral pulmonary nodules and a C2 body lesion concerning for metastasis. Biopsy of the lung lesions revealed a monomorphous population of optically clear cells with hyperchromatic and pleomorphic nuclei which were morphologically similar to the prior resection specimen. There are few reported cases of clear cell myoepithelial carcinoma arising from the hard palate, and there are even fewer reports on metastases to the lungs. Due to the low number of reported cases, prognosis and treatment of this neoplasm is not well defined.

Poorly differentiated vulvar squamous cell carcinoma within viral papillomas in a mare: immunohistochemical study

Present report describes the immunohistochemical diagnosis of poorly differentiated squamous cell carcinoma and involvement of papilloma virus in a mare. A five years old mare was brought to the Teaching Veterinary Clinical Complex with history of multi-lobulated haemorrhagic ulcerative mass in the vulvar region since last two months. The swollen region was aseptically prepared and the mass was resected out under local anaesthesia. Cytology of tumour revealed large cells with abundant basophilic cytoplasm and pleomorphic nuclei. Microscopically, presence of irregular cords of undifferentiated epidermal cells proliferating in downward fashion and invading dermis and subcutis were seen. AgNOR staining of section revealed 4 to 5 irregular, large dots or bizarre clusters in nuclei indicating malignancy. The PCR amplification was done by using specific primers for PVL1 gene of CPV that amplified a 480 base pair fragment of the Papilloma Virus L1 gene. Pancytokeratin immunolabeling was helpful in the diagnosing poorly differentiated squamous cell carcinoma. PCR confirmation suggested role of papilloma virus in induction and progression of squamous cell carcinoma.

Epithelial Myoepithelial Carcinoma of the Hard Palate: A Case Report with a Review of the Literature

Background: Epithelial myoepithelial carcinoma (EMC) is a rare biphasic tumour of the salivary gland with two cell types of inner ductal cells and outer layer of clear cells. In the literature, there are only a few reports of EMC originating from the hard palate. Case report: A 58-year-old female presented to the authors’ institution with partially submucosal lesion in the posterior aspect of the hard palate on the left side for 1 month. Biopsy was suggestive of a multinodular tumour with round to oval cells and a moderate number of pale eosinophilic to clear cytoplasm and round to oval, centrally to eccentrically placed, mildly pleomorphic vesicular nuclei suggestive of EMC of the hard palate. Immunohistochemically, cytokeratin (CK 5/6) showed strong cytoplasmic positivity highlighting the luminal epithelial cells. The myoepithelial cells showed strong nuclear positivity for p63 and cytoplasmic positivity for calponin. The patient underwent surgical resection of the tumour with a local flap cover and split skin graft and all the margins were negative in the final histopathological examination with erosion of the underlying bone. The patient was kept under observation and has been free of the disease for the past 12 months. Conclusion: Diagnosis of EMC is rare and is to be kept as a differential diagnosis during the evaluation of minor salivary gland tumours of palate.

Tubal choriocarcinoma in a ruptured ectopic pregnancy

Choriocarcinoma represents the most malignant entity in the spectrum of gestational trophoblastic disease. It can result from molar gestation in most instances and occasionally can arise after a term pregnancy, abortion, and ectopic pregnancy. Choriocarcinoma associated with tubal pregnancy is extremely rare and aggressive in its course with the incidence of 0.76%–0.4% of all ectopic pregnancies. This case report is from a 32-year-old female G2P1 + 0A1 whose last menstrual period was 4 months before presentation. She presented with a 2-day history of lower abdominal pain and vomiting. Histological sections of the fallopian tubal tissue showed extensive hemorrhage, necrosis and invasion by bizarre trophoblastic cells with large pleomorphic nuclei, irregular nuclear borders, and clumped chromatin.

Fractionated radiotherapy might induce epithelial-mesenchymal transition and radioresistance in a cellular context manner.

Despite the fact that radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that fractionated radiotherapy (FR) might confer radioresistance through epithelial-mesenchymal transition (EMT). Nevertheless, the effects of FR on EMT phenotype and the potential link between EMT induction and radioresistance development yet to be clarified. The aim of this study was to assess whether FR could promote EMT, and to elucidate if induction of EMT contributes to the acquisition of radioresistance. To this end, two human cancer cell lines (A549 and HT-29) were irradiated (2 Gy/day) and analyzed using wound healing, transwell migration and invasion assays, real-time polymerase chain reaction (for E-cadherin, N-cadherin, Vimentin, CD44, CD133, Snail, and Twist), clonogenic assay, Annexin V/PI, and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Irradiation of A549 (for 5 or 10 consecutive days) resulted in morphological changes including elongation of cytoplasm and nuclei and pleomorphic nuclei. Also, irradiation-enhanced migratory and invasive potential of A549. These phenotypic changes were in agreement with decreased expression of the epithelial marker (E-cadherin), enhanced expression of mesenchymal markers (N-cadherin, Vimentin, Snail, and Twist) and increased stemness factors (CD44 and CD133). Moreover, induction of EMT phenotype was accompanied with enhanced radioresistance and proliferation of irradiated A549. However, FR (for 5 consecutive days) did not increase HT-29 motility. Furthermore, molecular alterations did not resemble EMT phenotype (downregulation of E-cadherin, Vimentin, ALDH, CD44, CD133, and Snail). Eventually, FR led to enhanced radiosensitivity and decreased proliferation of HT-29. Altogether, our findings suggest that FR might induce EMT and confer radioresistance in a cell context-dependent manner.

Clues to recognition of fumarate hydratase-deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples.

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is rare and highly aggressive and is believed to arise mostly in the setting of hereditary leiomyomatosis-RCC syndrome with a germline mutation of FH. Because of the aggressiveness of these tumors and a frequent lack of ascertainable family history, these tumors may first present as metastases and be sampled by cytology. The cytologic findings of FH-deficient RCC have not previously been reported. Cytologic and limited biopsy samples from patients with FH-deficient RCC were reviewed retrospectively. In total, 24 cytologic and limited biopsy samples from 19 patients (6 women and 13 men; age range, 22-69 years) who had FH-deficient RCC and metastasis at presentation were evaluated. These included 21 cytology samples ranging from malignant effusions (n = 7) to metastases (n = 11), to samples of primary kidney tumors (n = 3). The samples exhibited cells, often in clusters and abortive papillae, with voluminous, finely vacuolated cytoplasm and large, pleomorphic nuclei with prominent, viral inclusion-like nucleoli. A distinctive finding of peripheral cytoplasmic clearing frequently was apparent, and intranuclear cytoplasmic pseudoinclusions were less frequent. Of 7 cell block and biopsy samples, several of which represented sampling from the same patient, all demonstrated tissue fragments that had discernable morphologic patterns associated with FH-deficient RCC, including tubulocystic and intracystic papillary growth. Features characteristic and suggestive of FH-deficient RCC may be identified in cytologic and small biopsy samples. Although the current samples were identified retrospectively in well characterized cases of FH-deficient RCC, the authors argue that, with appropriate clinical correlation, these features are sufficiently distinctive to trigger recognition and confirmatory workup.

Human Herpes Virus 6 (HHV-6)-associated Lymphadenitis: Pitfalls in Diagnosis in Benign and Malignant Settings.

Human herpes virus 6 (HHV-6) is a member of the β-herpesvirinae subfamily. Most people acquire HHV-6 primary infection early in life and reactivation may occur, most often in immunocompromised individuals, leading to various clinical manifestations. HHV-6 infected cells may be identified in lymph nodes in both reactive and neoplastic conditions. Cases were retrieved from the hematopathology consultation service archives at National Institutes of Health from 2003 to 2017 in which infection by HHV-6 had been documented by immunohistochemical stains to HHV-6 gp60/110 envelope glycoprotein. Five cases of reactive lymphadenitis and 3 cases of lymphoma; 2 angioimmunoblastic T-cell lymphoma and 1 classic Hodgkin lymphoma, positive for HHV-6 were identified. The reactive lymph nodes showed marked paracortical hyperplasia and admixed large atypical lymphoid cells exhibiting pleomorphic nuclei, vesicular chromatin, and prominent eosinophilic intranuclear inclusions. Vascular proliferation and necrosis were also present, raising suspicion of peripheral T-cell lymphoma. The 3 cases of lymphoma showed similar viral inclusions, in addition to the characteristic features diagnostic of the lymphoma. Staining for HHV-6 was positive with a membranous and Golgi pattern and was restricted to cells with evident inclusions on hematoxylin and eosin. HHV-6 infected cells were positive for CD3 and CD4. HHV-6 lymphadenitis can present with morphologic atypia creating a diagnostic pitfall for lymphoma. In such cases, careful attention to the characteristic viral inclusions can lead to immunohistochemical analysis highlighting the replicating virus. In cases of lymphoma, identification of the inclusions is key in detecting the associated infection as well as in avoiding misinterpretation of the lymphoma subtype.

Botryoid Rhabdomyosarcoma: Report of a Case

Rhabdomyosarcoma is a rare oral soft tissue malignant tumor with pathologic features that may influence the clinical behavior, treatment, and prognosis of the lesion. We report the case of a 13-year-old female patient presenting with an asymptomatic polypoid swelling in the left jugal mucosa measuring approximately 2.5 cm in diameter and of 3 months evolution. The presumptive diagnosis was fibrous hyperplasia. An excisional biopsy was carried out. Pathologic analysis revealed proliferation of predominantly ovoid cells, with eosinophilic cytoplasm and pleomorphic nuclei, arranged in the subepithelial cambium layer. The mucosal surface presented a papillary–verrucous appearance. Immunohistochemical analysis revealed intense positivity for desmin, myogenin, and ki67. The diagnosis was embryonal rhabdomyosarcoma (botryoid variant). The patient underwent complementary chemotherapy and radiotherapy, with no evidence of recurrence or metastatic disease at the 4-month follow-up. The clinical, histopathologic, immunohistochemical, and therapeutic aspects of botryoid rhabdomyosarcoma will be discussed.

Atypical Leiomyoma: a rare histologic variant - A Diagnostic Challenge

Bizarre or atypical leiomyoma (LM) is defined as “leiomyoma containing giant cells with pleomorphic nuclei and little or no mitotic activity.” Due to the ominous and worrisome microscopic appearance (many large giant cells with hyperchromatic, pleomorphic, malignant looking nuclei), this variant maybe misdiagnosed as a sarcoma. It, therefore presents a diagnostic challenge to the pathologist to accurately diagnose such a tumor while ensuring that a true malignancy is not overlooked. We report a case of a atypical leiomyoma of the uterus in a 40 year old female presenting with irregular menstrual bleeding. This highlights the need for extensive tissue sampling in such dubious cases to help arrive at a correct diagnosis.Bangladesh Journal of Medical Science Vol.17(3) 2018 p.511-514

Breast Carcinoma with Pulmonary Metastasis in Armadillo (Eupharactus sexcinctus)

Background: Breast neoplasms are among the most common neoplastic conditions affecting domestic animals and are considered the most common type of cancer affecting women, bitches, and cats. However, there are few reports on breast neoplasms in wild animals, and there is no record of their occurrence in armadillos worldwide. Breast neoplasms are hormone-dependent neoplasms that often cause lymph node and pulmonary metastases. The diagnosis is based on the patient’s history, complete physical examination, and complementary tests. Here we report a case of mammary neoplasia with pulmonary metastasis in an armadillo (Euphractus sexcinctus).Case: A senile female armadillo was referred to us for treatment with a history of hyporexia and nodules in both breasts. Ultrasonographic examination revealed a hypoechogenic nodular lesion with a cross-section of approximately 1.3 × 1.4 cm and well-defined borders. The lesion had a circumscribed aspect in the left mammary gland. In the right mammary gland, there was a heterogeneous lesion with cystic formations and anechoic content. Cytopathological examination of the nodules was performed by fine needle aspiration cytology and revealed the presence of epithelial cells with ovoid and aberrant nuclei, anisocariasis, binucleation, coarse chromatin, and a high nucleus to cytoplasm ratio suggestive of carcinoma. The animal had a lean body score due to hyporexia that had evolved to anorexia and was undergoing supportive treatment. Nevertheless, the animal died two months after the cytologic diagnosis. A necropsy was performed. Cutting of the breast nodules revealed a hardened pale yellow material. The animal had pronounced pleural effusion, hemorrhage, and numerous pale yellow nodules of various sizes with firm consistency throughout the lung parenchyma. It also had hepatomegaly and splenomegaly. Fragments of various organs were fixed in 10% buffered formalin, routinely processed, embedded in paraffin, and stained with hematoxylin and eosin. Upon microscopic examination, the mammary nodes demonstrated a proliferation of epithelial cells organized into tubular structures with intraluminal papillary projections. The cells had a polyhedral profile and a high nucleus to cytoplasm ratio, moderately pleomorphic evident nuclei. Some cells had coarse chromatin. We observed moderate anisocytosis and anisocariasis, as well as mitotic figures. In the lungs, nodules with the same microscopic characteristics of the mammary nodes were observed in addition to intense congestion and multifocal hemorrhages.Discussion: This type of mammary carcinoma is considered an invasive neoplasm of ductal origin, and is morphologically characterized by rounded, ovoid, or angulated tubule formations with intraluminal projections. The patient’s prognosis is directly related to the occurrence of vascular invasion and metastasis. If present, these conditions may lead to reduced patient survival. Since the lungs are the most common sites of metastasis, pleural effusion caused by vessel erosion due to the presence of tumors is common and can in most cases lead to respiratory failure and eventually death. In this case, the association between the necropsy findings and the results of the histopathological examination enabled us to classify the carcinoma as one of mammary origin and of the tubulopapillary type with pulmonary metastasis. This is the first report of mammary carcinoma in an armadillo in captivity in the world.

Pleomorphic Lobular Carcinoma In Situ, what do we know? A UK multicenter audit

Aims: Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively newly described pathological lesion that is distinguished from classical LCIS by its large pleomorphic nuclei. The lesion is uncommon and its appropriate management has been debated. The aim of this study is to review data from a large series of PLCIS to examine its natural history in order to guide management plans.

MEDIASTINAL YOLK SAC TUMOR INFILTRATING THE HEART

As a rare tumor, yolk sac tumor is a type of neoplasm that appears like the yolk sac, extraembryonic mesenchyme, and allantois. The mediastinum is the second most frequent area after the gonadal area. We present an extremely rare case of 15years old boy with mediastinal yolk sac tumor. The boy came with the chief complaint of swelling of the neck and face. Computed tomography scan of the chest revealed bulky mass with a cystic component that infiltrated the heart. The diagnosis of mediastinal yolk sac tumor was made after core needle biopsy. Histopathologic analysis revealed tumor mass with solid and microcystic structure and pleomorphic nucleus within the tumor cells. Laboratory finding showed elevated serum alpha-fetoprotein level reaching more than 8000ng/ml. Echocardiography revealed a mass in the right atrium. The patient condition was rapidly deteriorated due to his vena cava superior syndrome. Unfortunately, the patient died two days after diagnosis and we did not have the chance to do the therapy. Mediastinal yolk sac tumor is a rare malignancy that requires comprehensive management. The diagnosis should be made based on histopathological findings with the addition of thoracic computer tomography scan to assess the degree of infiltration to surrounding organ. A life-threatening condition such as vena cava superior syndrome should be assessed promptly to allow for immediate treatment.

Lack of MDM2 interpretation guidelines contribute to diagnostic difficulty in a case of undifferentiated sarcoma

Undifferentiated sarcomas are malignant mesenchymal neoplasms lacking any specific line of differentiation and are typically a diagnosis of exclusion requiring supplemental diagnostic testing. We present a case of a 68 year old male with a thigh mass. Microscopic evaluation revealed a spindle and epithelioid cell neoplasm with pleomorphic nuclei arranged in vague, irregular fascicles and positive nuclear MDM2 staining. Fluorescence in situ hybridization (FISH) analysis demonstrated 36.2 average MDM2 signals and 31.7 average centromere 12 signals per cell (1.1 ratio). Although a dedifferentiated liposarcoma is defined by MDM2 amplification, the lack of an adjacent well differentiated liposarcoma component and radiographic characteristics argued against a lipomatous tumor in this case, leading to a diagnosis of undifferentiated sarcoma, despite the markedly increased MDM2 copy number. With expanding utilization of molecular and cytogenetic testing of tumors, this case highlights questions regarding the interpretation and incorporation of these results in diagnostic soft tissue pathology.

Mandibular Odontogenic Fibrosarcoma in Pickhandle Barracuda (Sphyraena jello Cuvier, 1829)

The spontaneous occurrence of mandibular odontogenic fibrosarcoma is reported in pickhandle barracuda (Sphyraena jello) from Parangipettai fish landing centre, southeast coast of India. The gross morphology revealed reddish-white, fleshy distended tumours in and around the intraoral bone musculature. The necropsy examination showed no gross evidence of local invasion and distant metastasis into visceral organs. Histopathologically, tumours were characterized by abundant hyperplastic small spindle cells arranged into well-defined interwoven bundles. The spindle cells presented scant fibrillar cytoplasm, and oval to elongated hyperchromatic and pleomorphic nuclei. The ultrastructure of mandibular lesions was composed of differentiated fibroblasts with nuclei enveloped by a thin rim of cytoplasm with denser heterochromatin and lighter euchromatin. Mitotic figures were seen in high numbers of cells, telophase of the karyokinesis was observed. No virus particles were observed in the examined lesions. Based on the histological and ultra-structural findings, this tumour was diagnosed as mandibular odontogenic fibrosarcoma in S. jello.

Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour

BackgroundLiposarcoma is an extremely rare primary bone sarcoma.Case presentationWe report a case of primary pleomorphic liposarcoma that arose in an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly isointense on T1- and high-signal on T2-weighted sequences with focal areas of increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right distal femur and multiple small pulmonary metastases. Histologically, the tumour was a pleomorphic liposarcoma containing large tumour cells with vacuolated cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in extensive (> 95%) necrosis in the primary tumour and almost complete resolution of the femoral and pulmonary metastases.ConclusionsPleomorphic liposarcoma can present as a sclerotic primary malignant bone tumour; markers of adipose differentiation are useful in histological diagnosis and neoadjuvant MAP chemotherapy results in significant tumor necrosis.

329 Unique Genomic Alterations in a Case of Splenic Angiosarcoma

Angiosarcoma of the spleen is an uncommon condition, comprising only 2.7% of all angiosarcomas. It is common for splenic angiosarcoma to metastasize to other organs. The diagnosis of splenic angiosarcoma is made by either acute abdominal symptoms after splenic rupture or incidentally from radiologic surveillance. We report herein a case of splenic angiosarcoma with documented unique genomic mutations that have not been previously reported. An 81-year-old man presented with thrombocytopenia and progressive splenomegaly over several years; a diagnosis of immune thrombocytopenia purpura was initially made. The patient subsequently developed sclerotic-blastic bone lesions with worsened splenomegaly. Bone marrow and bone biopsies revealed angiosarcoma, which was considered to be metastatic from the spleen based on imaging. He received multiple cycles of chemotherapy with minimal improvement. Eventually, the patient underwent splenectomy and the diagnosis of primary splenic angiosarcoma was made. Tissue sections showed a mitotically active cellular spindle cell neoplasm with pleomorphic nuclei, diffusely configured in anastomosing vasoformative channels. Zones of fibrosis, infarction, or active tumor necrosis comprised less than 5% of the splenic volume. Metastases to lymph nodes, peripancreatic fat and bone marrow were documented. Immunostains showed diffuse and strong immunoreactivity for CD31 and CD34, supporting a vascular origin. Molecular testing showed mutations in the following genes: ATRX, CDKN2A/B, EPHA3, MLL2, NOTCH2, and TET2. Primary splenic angiosarcoma is a rare entity with limited published molecular data. To our knowledge, the composite of genomic mutations outlined herein have not been previously reported in splenic angiosarcomas. CDKN2A/B has been reported in hepatic angiosarcomas.