Geographic Areas Of Necrosis Research Articles

A Rare Case of a Malignant Epithelioid Neoplasm With an Underlying Novel EWSR1::ZBT44 Fusion, Identified on Next-Generation Sequencing (NGS).

The clinicopathological spectrum of undifferentiated round cell sarcomas of bone and soft tissues is expanding after the 5th edition of the WHO classification. A 23-year-old male patient presented with a lump in his left thigh of 3 months' duration. Radiological examination revealed a well-defined, solid-cystic lobulated, soft tissue lesion in the proximal medial region of his left thigh, measuring 7.7 cm in the largest dimension. The referring diagnosis was an epithelioid sarcoma. Histopathological review of the tumor sections revealed a cellular tumor composed of malignant epithelioid to focally "rhabdoid-like" cells in a variable hyalinized and myxoid stroma with geographic areas of necrosis. In addition, there were areas reminiscent of hemangiopericytomatous vasculature. By immunohistochemistry, the tumor cells were diffusely positive for CD34, focally and distinctly for pan keratin (AE1/AE3). INI1/SMARCB1 and SMARCA4 (BRG1) were diffusely positive (normal). Next-generation sequencing with a wide sarcoma panel revealed EWSR1exon8::ZBT44exon4 fusion. The present example constitutes the first malignant epithelioid tumor with a hemangiopericytomatous growth pattern, exhibiting this rare fusion. The differential diagnoses of this tumor and their corresponding immunohistochemical profile are discussed. This example highlights the value of NGS in unraveling rare fusions and in differentiating these tumors from their several mimics.

Metastatic Malignant Peripheral Nerve Sheath Tumor to the Brain Demonstrating Clonal Evolution by Cytogenetic Analysis

Abstract Casestudy: Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive, uncommon soft tissue sarcomas that arise from peripheral nerves or pre-existing benign nerve sheath tumors. Local recurrence and metastases are known to occur, though metastasis to the brain is very rare. Limited treatment options impart the need to better characterize these tumors. We present a case of a 26-year-old female with a history of a 5.5 cm MPNST of the left chest, who presented with brain metastasis two years later. The tumors were found to have similar histologic and cytogenetic findings with clonal evolution evident in the metastasis. The original tumor exhibited a proliferation of spindled cells arranged in sweeping fascicles accompanied by numerous mitotic figures and areas of geographic necrosis. The malignant cells were patchy positive for S100 and CD34 and negative for SOX10 and GFAP. Cytogenetic analysis revealed three related abnormal clones, all of which demonstrated add(2)(p25) and add(22)(q12). Monosomy 6 was identified in one clone, and near triploidy and triploidy was identified in the other two clones. Additionally, numerous whole chromosome gains and losses were present. The patient underwent surgical resection and was treated with adjuvant radiation. Two years later, a PET scan revealed a hypermetabolic left temporal lobe mass. MRI revealed a 4.9 x 4.5 cm destructive lesion invading through the temporal bone and involving brain parenchyma. The mass was resected and submitted for pathologic evaluation revealing similar histologic findings to the original, though S100 and SOX-10 were negative. Cytogenetic analysis revealed two related abnormal clones which shared add(2)(p25) and add(22)(q12) as well as an additional copy of add(22)(q12). One clone showed near triploidy with loss of several whole chromosomes. These findings are remarkable for recurrent metastatic disease to the brain and uniquely show clonal evolution of the metastatic tumor.

Mixed Neuroendocrine-Nonneuroendocrine Carcinoma Arising in the Gallbladder: A Rare Case of a Three-Component Composite Neoplasm

Abstract Introduction Neuroendocrine gallbladder neoplasms are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. Interestingly, those neoplasms can also be observed along with other malignant components of epithelial origin, mostly adenocarcinomas. Herein we report an unusual case of a patient with a gallbladder neoplasm composed of a neuroendocrine carcinoma, a squamous cell carcinoma, and an adenocarcinoma. Methods The patient was a 62-year-old woman who presented with right upper quadrant abdominal pain with a positive Murphy’s sign on physical examination. She was clinically diagnosed with acute cholecystitis and underwent cholecystectomy. Gross examination showed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma and an adjacent high-grade neuroendocrine carcinoma; each of these two components composed more than 30% of the neoplasm and infiltrated into the perimuscular connective tissue with no serosal involvement. Additionally, a superficial adenocarcinoma component was also seen composing 10% of the neoplasm. The squamous cell carcinoma showed moderate differentiation with areas of keratinization; it was positive for Ck7, p40, and p63. The neuroendocrine carcinoma showed areas of geographic necrosis, and the cells had inconspicuous nucleoli and granular chromatin, with numerous mitotic figures; it was positive for synaptophysin and chromogranin. The adenocarcinoma showed gland formation with mucicarmine stain, highlighting the mucin within the neoplastic cells; it was positive for Ck7 but negative for p40. Subsequently, the patient underwent resection of the liver bed, which was negative for metastasis, and was then referred for chemotherapy. Conclusion Our review of the literature revealed seven documented cases of three-component gallbladder neuroendocrine neoplasms. Generally, patients with these tumors have a poor prognosis, and due to their rarity, no specific treatment guidelines have yet been established. It has been suggested that a multipotent common stem cell is the origin of these tumors.

Carcinosarcoma of the Pancreas: Case Report of a Rare Type of Pancreatic Neoplasia

Carcinosarcoma of the pancreas: case report of a rare type of pancreatic neoplasia Introduction Carcinosarcoma of the pancreas is a rare type of pancreatic neoplasms and only few cases of carcinosarcoma have been reported in the literature. Carcinosarcoma of the pancreas have cells recognizable as adenocarcinoma as well as sarcomatous components. We present a rare case of pancreatic carcinosarcoma. Case Presentation: An 85 year-old male was transferred to our hospital for further management of pancreatic mass. He presented to outside hospital with complains of abdominal pain, jaundice and weight loss. Imaging showed a mass in the head of the pancreas. Endoscopic ultrasound (EUS) showed a 7.5 cm X 7.0 cm hypoechoic mass in the head of pancreas (figure 1). EUS guided fine needle biopsy suggested an atypical spindle and myxoid type sacrcoma. No evidence of distant metastasis was identified. An extended pancreaticoduodenectomy was performed. We will plan for adjuvant chemotherapy after adequate postoperative recovery. Grossly, the tumor consisted of a 12.0 x12.0 x 8.0 cm soft mass localized in head of the pancreas with extension into duodenum and peripancreatic soft tissue (Figure 2). Histologically, the tumor showed two components. Sections of the tumor showed a high-grade sarcomatoid component with myxoid features, some floret like cells, many mitotic figures and geographic areas of necrosis. There was focal cartilaginous differentiation. In addition there was a glandular component consistent with invasive ductal adenocarcinoma (Figure 3). Immunostains were also used in evaluation and the overall findings were consistent with carcinosarcoma (pT3pNo).Figure 1Figure 2Figure 3Discussion: Carcinosarcomas are rare tumors characterized by a carcinomatous and a sarcomatous component. Carcinosarcomas are predominantly located in the uterus and only few cases of carcinosarcoma of pancreas have been reported in literature. These tumors have cellular elements derived from two different histological origins proliferating in one tumor. Although controversial but several studies have suggested a monoclonal origin for carcinosarcomas using diverse immunohistochemical and molecular analyses. EUS guided core needle biopsy of pancreatic mass was not specific and only showed the sarcomatous component in our patient. Based on the very limited number of reported cases, the prognosis of carcinosarcoma of the pancreas appears dismal.

Catastrophic Multi-Organ Failure with Bone Marrow Necrosis in a Sickle Cell Beta Plus Thalassemia Patient

The variant sickle cell hemoglobinopathies have a variety of phenotypic presentations. Sickle cell beta plus thalassemia is an uncommon variant with an incidence that is 1/10th of sickle cell trait. This phenotype usually is associated with a milder clinical course, however often the first clinical presentation of such patients can be fatal vaso-occlusive crisis. Our case involves a 47 year old African American male with a reported history of sickle cell trait presenting with acute on chronic lower back pain for which an organic cause could not be identified with plain Xrays. He was treated with benzodiazepines and narcotics and later admitted to the ICU after being found unresponsive at home. He required intubation for airway protection. He was started on a Narcan drip for presumed narcotic overdose, without improvement. Noncontrast CT imaging of the head was negative. Laboratory findings were significant for anemia, thrombocytopenia, leukocytosis, acute kidney injury and elevated liver enzymes. Hemolysis was suspected with a markedly elevated LDH. Peripheral smear showed mild microangiopathic changes with 0-1 schisctocytes per hpf without evidence of sickle cells. Hematology was consulted and the patient was started on plasma exchange for a presumed diagnosis of TTP, however it was discontinued when his ADAMTS13 returned at a low-normal 67%, and TTP was felt less likely. MRI of the brain showed multiple focal and patchy areas infarcts throughout white matter of both cerebral hemispheres. MRI of the lumbar and thoracic spine showed a heterogeneous appearance of the bone marrow, concerning for a marrow infiltrative process. Work up for infectious or vasculitic causes were unremarkable. Hemoglobin electrophoresis showed Hb A1 20.2 (L), A2 5.8 (H), Hb F 2.2 (H), Hb S 71.8 (H), identifying doubly heterozygous sickle cell beta plus thalassemia. Bone marrow biopsy was hyperplastic with areas of geographic necrosis with sickle cells causing sludging and congested sinusoidal spaces suggesting ischemic necrosis due to vaso-occlusion. He was treated with exchange transfusion, with repeat hemoglobin electrophoresis showing A1 73.2 (L), A2 3.5 (H), HbS 23.3 (H). His lupus anticoagulant was positive raising concern for APLAS contributing to his catastrophic clinical course and severe neurologic disease,so he was started on anticoagulation with Lovenox and high dose steroids at a dose of 1 mg/kg daily. When the anticardiolipin and beta2 glycoprotein antibodies returned negative, the steroids were tapered and eventually discontinued. The clinical significance of the lupus inhibitor remains unclear. Shortly after initiation of plasma exchange and simple transfusion, the patient did stabilize hematologically. Platelets returned to the normal range and there was no evidence to suggest ongoing hemolysis. Renal and liver function improved. However he made no neurological recovery. He continued to require ventilator support and underwent a tracheostomy. A repeat MRI head showed progressive infarcts of both cerebral hemispheres, with new cerebellar infarcts. He was declared brain dead after 23 days and care was withdrawn. This case demonstrates that sickle cell beta plus thalassemia can present with acute hemolysis and bone marrow necrosis in otherwise healthy adults. The literature supports bone marrow necrosis and subsequent fat emboli as the likely pathophysiologic nidus responsible for multiorgan system failure including the catastrophic neurologic insult in this patient. Prompt recognition of this uncommon and challenging disease presentation and timely treatment with exchange transfusion may lead to improved clinical outcomes. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary cutaneous NK/T cell lymphoma-nasal type with cutaneous aspergillosis. A case report and literature review

We report a 66-year-old male who presented with a blackish discolored ulcerated nodule over the right flank of 2 months duration. Biopsy of the lesion revealed ulcerated epidermis with fungal hyphae of Aspergillus overlying dense, angiocentric atypical lymphoid infiltrate involving the dermis, and extending into sub cutis with geographic areas of necrosis. The patient had three episodes of cutaneous recurrence over a three year period. The cutaneous lymphoid infiltrates showed similar immunohistochemical profiles: LCA+, CD3€+, CD20- and CD56-. CD30 was positive in a small percentage of cells. P53 proliferation marker was strongly positive.There was no evidence of systemic involvement by the neoplastic lymphoid and fungal infiltrates. This is one amongst the rare reports of cutaneous aspergillosis with primary cutaneous NK/T cell lymphoma nasal-type.

Asymptomatic polypoidal intracavitary cardiac metastases from pulmonary adenocarcinoma

A young male presented with right flank pain, fever, cough, loss of weight and appetite. CT of the abdomen revealed a right suprarenal cystic mass measuring 10×8 cm with para-aortic...

A case of complete heart block reverting to normal sinus rhythm after treatment for cardiac invasive Burkitt’s lymphoma

Dear Editor, A 42-year-old man was transferred to our hospital after presenting with syncope. Approximately 3 and 6 weeks before admission, the patient had been involved in two separate fights resulting in significant facial injury and swelling. The patient did not seek immediate medical attention but persistent pain prompted evaluation at our hospital 10 days before the relevant admission. At that time, a computed tomography (CT) of the head and facial bones demonstrated facial fractures and an expansile opacification of the right maxillary sinus with erosive change of the adjacent osseous structures and contiguous abnormal soft tissue extending into the periantral fat and extraconal orbit (Fig. 1a). The radiographic differential was an infected mucocele with concomitant osteomyelitis versus a neoplastic process, and thus, biopsy was recommended. The patient was taken to the operating room, and a biopsy of the mass was performed. He was given antibiotics for a presumed infected mucocele with osteomyelitis and discharged with plans to follow-up in 1 week as an outpatient for the pathology results. Before his follow-up appointment, he presented to an outside hospital with complaints of syncope with pre-syncopal dizziness. By this time, the pathology results from the initial maxillary biopsy had revealed sheets of tumor composed of primitive cells with round hyperchromatic nuclei and prominent nucleoli (Fig. 2). Numerous large cells with clear cytoplasm were scattered through the tumor in a starry-sky-type pattern. The tumor appeared to be proliferating rapidly with frequent mitoses and geographic areas of necrosis. Immunohistochemical staining indicated B-cell lineage with aberrant CD10 coexpression and an extremely high proliferative index. The in situ hybridization study for Epstein Barr virus (EBV) genome was positive. Together, the findings were consistent with a diagnosis of Burkitt’s lymphoma. He was transferred to our hospital for further management. At the time of transfer, the patient was disheveled but in no acute distress. Before the diagnosis of the facial fracture, his medical history had been unremarkable other than surgical repair of an inguinal hernia. He was not taking medications other than acetaminophen and hydrocodone for pain and amoxicillin/clavulanate since his recent discharge. He had a complicated social history. He had been previously married but was divorced and was currently homeless. In the 1 to 3 years before admission, he had unprotected sexual intercourse with both men and women. He denied injection drug use but admitted to heavy alcohol use, as well as recreational cocaine and marijuana. He had smoked one to two packs per day for 27 years. His blood pressure was 123/67 mmHg, and his pulse was bradycardic in the 50 s. His physical exam was notable for a left-eye periorbital ecchymosis and right temple edema without ecchymosis, status post surgical incisions. He had bilateral mild axillary lymphadenopathy but no other evidence of lymph node enlargement. Cardiovascular exam was notable for a regular, bradycardic rhythm without murmur, gallop, Ann Hematol (2007) 86:687–690 DOI 10.1007/s00277-007-0290-x

Extensive myocardial infiltration by hemopoietic precursors in a patient with myelodysplastic syndrome

BackgroundAlthough myocardial infiltration with leukemic blasts is a known finding in patients with acute leukemia, this phenomenon in myelodysplasia is not reported in the literature. Cardiac symptoms in patients with myelodysplasia are often due to anemia and may be due to iron overload and side effects of therapy.Case presentationHerein we report the first case of neoplastic infiltration of the heart with associated myocardial necrosis in a patient with myelodysplasia. It was associated with unicellular and multifocal geographic areas of necrosis in the left ventricle and the interventricular septum. It is likely that cardiac compromise in our patient was due to a combination of restrictive cardiomyopathy due to leukemic infiltration, concomitant anemia, cardiac dilatation, conduction blocks and myocardial necrosis. Myocardial necrosis was most likely due to a combination of ischemic damage secondary to anemia and prolonged hypotension and extensive leukemic infiltration. Markedly rapid decrease in ejection fraction from 66% to 33% also suggests the role of ischemia, since leukemic infiltration is not expected to cause this degree of systolic dysfunction over a 24-hour period. The diagnosis was not suspected during life due to concomitant signs and symptoms of anemia, pulmonary infections, and pericardial and pleural effusions. The patient succumbed to cardiac failure.ConclusionHemopoietic cell infiltration was not considered in the differential diagnosis and contributed to this patient's morbidity and mortality. This case highlights the clinical importance of considering myocardial infiltration in patients with myelodysplasia and cardiac symptoms.

Cytokeratin 7 and 20 expression in epithelioid sarcoma.

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor of uncertain histogenesis that arises predominantly in the extremities of young adults. Immunohistochemically, the neoplastic cells are typically positive for vimentin, low molecular weight cytokeratin (CAM5.2) and epithelial membrane antigen (EMA). We examined eight cases of ES from seven different patients. All cases were studied with immunohistochemistry for EMA, CAM5.2 (keratin 8 and 18), 34BE12 (keratins 1, 5, 10 and 14/15), cytokeratins 7 and 20 (CK7, CK20), and CD34. The average patient age was 53 (range 43-76) and the male:female ratio was 5:2. The location was the upper extremity in five tumors, the lower extremity, the perineum, and the paraspinal soft tissue in one tumor each. All cases contained predominantly epithelioid cells, but spindle cells were also present in three cases. All cases contained areas of geographic necrosis. CAM5.2 was strongly positive in seven tumors and focally positive in one (8/8). EMA was diffusely positive in two cases and focally positive in five cases (7/8). CD34 was diffusely positive in 3/8 cases. 34BE12 was diffusely positive in one case and focally positive in two others (3/8). CK7 was diffusely positive in one case and focally positive in another (2/8). CK20 was negative in all cases (0/8). All cases tested were positive for vimentin (6/6), 2 cases were focally positive for HHF35 (2/5), and all cases tested were negative for S-100 protein (0/7). In addition to the known immunoreactivity for CAM5.2 and EMA, there is positivity for CK7 and 34BE12 in a small proportion of cases. None of the cases expressed CK20. This immunophenotypic profile suggests that ES is more similar to carcinoma and synovial sarcoma than to other soft tissue tumors, and may be of diagnostic utility.

Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: Frequency of Epstein-Barr virus and other features associated with immunosuppression

We recently reported two cases of reversible Epstein-Barr virus (EBV)—associated lymphomas in patients undergoing methotrexate therapy for rheumatic disease. The current study was undertaken to investigate how frequently lymphoid neoplasms in patients with rheumatic disease show features of lymphoproliferations occurring in immunocompromised patients. Eighteen patients (including the two previously reported patients) with rheumatoid arthritis or dermatomyositis who developed lymphoproliferative lesions and on whom detailed clinical information was available were studied. As a group these patients developed a spectrum of lymphoproliferative lesions; however, a subset of patients developed neoplasms with features associated with immunosuppression. The neoplasms occurred in extranodal sites in 10 (56%) patients, showed a diffuse large-cell histology in nine (50%) patients, and contained EBV (EBER1) transcripts and EBV latent membrane protein in six (33%) patients. In three (17%) patients the neoplasms showed the entire constellation of features typical of immunosuppression-associated lymphoproliferations, including extranodal location, large-cell or polymorphous histology, geographic areas of necrosis, and the presence of EBV. These three patients were receiving both steroids and methotrexate at the time they developed their neoplasms. The findings of this study support the hypothesis that a subset of lymphoid neoplasms in rheumatic patients occurs in an immunocompromised setting and suggest that therapeutic immunosuppression may contribute, at least in part, to the development of these lymphoid neoplasms.

Surgical Pathology of the Lung in Wegenerʼs Granulomatosis

We report the pulmonary pathologic features in 87 open lung biopsies from 67 patients with Wegener's granulomatosis (WG) who were treated at a single institution from 1968 to 1990. At the time of open lung biopsy, 48 patients (72%) had classical WG with renal involvement; 19 (28%) had limited WG without renal involvement. The pathologic features were divided into major and minor manifestations. In the 82 specimens demonstrating no infectious organism, the three major pathologic manifestations of classical WG observed were also useful diagnostic criteria and included: (a) parenchymal necrosis, (b) vasculitis, and (c) granulomatous inflammation accompanied by an inflammatory infiltrate composed of a mixture of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils. Parenchymal necrosis was found in 84% of biopsy specimens either as neutrophilic microabscesses (65% of specimens) or as large (67%) or small (69%) areas of geographic necrosis. Areas of geographic necrosis were usually surrounded by palisading histiocytes and giant cells. Additional granulomatous lesions consisted of microabscesses surrounded by giant cells (69%), poorly formed granulomas (59%), and scattered giant cells (79%). Sarcoid-like granulomas were uncommon (4%), and in only one specimen (1%) appeared within an inflammatory lesion of WG. Vascular changes were identified in 94% of biopsy specimens. Vascular inflammation was classified as chronic (37% arterial, 64% venous), acute (37% arterial, 29% venous), non-necrotizing granulomatous (22% arterial, 9% venous), and necrotizing granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was relatively uncommon (11% arterial, 6% venous). Cicatricial changes were found in arteries in 41% of biopsy specimens and in veins in 16%. Capillaritis was present in 31% of specimens. Minor pathologic lesions were commonly observed in biopsy specimens associated with classical WG lesions, but they were usually inconspicuous and not useful diagnostic criteria. These included interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue eosinophils (100%), organizing intraluminal fibrosis (70%), endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and a variety of bronchial/bronchiolar lesions including acute and chronic bronchiolitis (51% and 64%), follicular bronchiolitis (28%), and bronchiolitis obliterans (31%). These minor lesions were often found at the periphery of typical nodules of WG. However, in 15 specimens (18%) a minor pathologic feature represented the dominant or major finding: pulmonary fibrosis (six specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%), lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans with organizing pneumonia (BOOP), and bronchocentric granulomatosis (one specimen, 1%).(ABSTRACT TRUNCATED AT 400 WORDS)