Elliot Weisenberg

Pathologic Quiz Case

65-year-old white woman presented to her primary care physician with the complaint of right upper quadrant pain. Her medical history was remarkable for hypertension, diabetes mellitus, and asthma. She was evaluated for cholelithiasis, and gallstones were detected. A 6.0-cm right adrenal mass was detected by computed tomographic scan (Figure 1). Evaluation of the chest, abdomen, and pelvis, including computed tomographic scanning and magnetic resonance imaging revealed no other lesions. Determination of urinary cortisol and vanillylmandelic acid levels showed no evidence of a functioning tumor. Cholecystectomy and excision of the right adrenal mass were performed. The gallbladder showed chronic cholecystitis and cholelithiasis. The right adrenalectomy specimen consisted of an 8.0 3 7.5 3 5.5-cm ovoid mass with a focally hemorrhagic surface. The hemorrhagic oval mass formed nearly 90% of the specimen, was fairly well circumscribed, and was surrounded by a rim of flattened adrenal tissue. Cut section revealed a variegated cut surface (Figure 2). Histopathologic examination revealed ovoid nests, papillary fronds, and solid areas of tumor cells, which on occasion formed vascular channels containing red blood cells. The tumor cells were large, round to oval, and markedly atypical with moderately abundant amphophilic cytoplasm and poorly developed cell borders. The nuclei were vesicular, round to oval, and contained prominent eosinophilic nucleoli. Brisk mitotic activity was present, and atypical mitotic figures were identified. Occasional intracytoplasmic lumina contained red blood cells (Figure 3). The tumor infiltrated residual adrenal cortical tissue in small clusters and as single cells. The capsule of the adrenal capsule appeared intact. Immunohistochemical studies showed strong staining for factor VIII‐related antigen (Figure 4), vimentin, and focal positivity for pancytokeratin. Staining for neuron specific enolase and synaptophysin were not detected. What is your diagnosis?

Testicular Natural Killer/T-Cell Lymphoma, Nasal Type, of True Natural Killer-Cell Origin

The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3 epsilon. In situ hybridization showed diffuse positivity for Epstein-Barr virus-encoding RNA. The results of gene rearrangement studies for the gamma chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.

Gastric toxoplasmosis in a patient with acquired immunodeficiency syndrome. A case report and review of the literature.

Toxoplasmosis is a common opportunistic pathogen in patients with acquired immunodeficiency syndrome (AIDS). It usually presents with ocular, central nervous system, or pulmonary disease. Gastric toxoplasmosis is uncommon in AIDS patients, especially in the absence of central nervous system manifestations. In the few reported cases, patients have presented with abdominal pain and other digestive complaints that usually are attributed to the more common gastrointestinal manifestations of human immunodeficiency virus infection. We describe a 49-year-old man with AIDS who presented with abdominal pain, diarrhea, dry cough, and systemic symptoms and was diagnosed with toxoplasmosis by a gastric biopsy.

Genetic Evidence That Intratumoral T-cell Proliferation and Activation Are Associated with Recurrence and Survival in Patients with Resected Colorectal Liver Metastases

Maker and colleagues analyzed liver tumor specimens and outcomes from 96 patients with colorectal cancer liver metastases and report that genetic evidence of T-cell activation/proliferationin liver tumors, specifically the increased expression of TNFSF14/LIGHT, is associated with longer overall and disease-free survival. Though immune responses correlate with prognosis in primary colorectal cancer, the role of tumor immunity in metastatic disease is less clear. We hypothesized that patient survival and tumor recurrence correlate with transcriptional evidence of lymphocyte proliferation/activation in resected colorectal cancer liver metastases (CRLM). Microarray gene analysis was performed on liver tumor specimens from 96 patients who underwent resection for CRLM. A Cox proportional hazards model identified genes associated with overall survival (OS) and recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment analysis ranked biologically relevant processes. Survival probabilities of prioritized processes were assessed. Protein expression was validated with immunohistochemistry in an independent set of patients. GO analysis identified and ranked unique biologic processes that correlated with survival. Genes that specifically functioned in the biologic process of “T-cell proliferation” were significant predictors of OS (P = 0.01), and both “T-cell proliferation” and “activation” were highly associated with RFS (P ≤ 0.01). Analysis of genes in these GO categories identified increased TNFSF14/LIGHT expression to be most associated with improved OS and RFS (P ≤ 0.0006). Immunohistochemistry of an independent validation set of CRLM confirmed that both increased tumor-infiltrating lymphocytes (TIL) and higher LIGHT expression on TILs were associated with improved OS and RFS. Differential expression of genes involved in T-cell proliferation/activation was associated with survival outcomes in a large number of surgical patients who underwent resection of CRLM. These biologic functions determined by GO analysis of the tumor microenvironment have identified specific immune-related genes that may be involved in an antitumor immune response. Cancer Immunol Res; 3(4); 380–8. ©2015 AACR.

Malignant Sertoli cell tumor of the ovary metastatic to the lung mimicking neuroendocrine carcinoma: Report of a case

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis

An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV–VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40 % after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV–VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors.

Simultaneous Occurrence of Glandular and Neuroendocrine Components in Lymph Node Metastasis of Gastric MANEC.

A 70-year-old male presented with anemia and dysphagia. Upper endoscopy revealed a 6.9 cm mass extending from the gastroesophageal junction to the body of the stomach. Biopsy of the mass demonstrated Grade 2 adenocarcinoma, and endoscopic ultrasound evaluation determined uT3N1 staging. The patient underwent staging exploratory laparoscopy with negative peritoneal washings and was initiated on neoadjuvant ECF (epirubicin, cisplatin, and 5-fluorouracil) chemotherapy. Post-chemotherapy crosssectional imaging and positron emission tomography scanning confirmed response to therapy, and the patient underwent a total gastrectomy with D2 lymphadenectomy. Resection margins were free of malignancy, abundant residual tumor was present, and 6 of 20 lymph nodes were positive for metastasis (ypT3 ypN2). In addition to a moderately differentiated adenocarcinoma, the stomach incidentally contained foci of neuroendocrine hyperplasia in and around the main tumor. There was also a well to moderately differentiated neuroendocrine tumor, immunoreactive for synaptophysin, grossly identified separately from the adenocarcinoma. Furthermore, the adenocarcinoma showed areas of neuroendocrine differentiation, 578474 IJSXXX10.1177/1066896915578474International Journal of Surgical PathologyAugust et al research-article2015

Dedifferentiated gastrointestinal stromal tumor arising de novo from the small intestine

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and usually display monotonous cytologic features and immunoactivity for CD117. Anaplastic GIST, with pleomorphic cells and loss of CD117, until recently have only been reported in patients with chronic imatinib mesylate treatment. Dedifferentiated GISTs arising de novo is a newly identified entity that may prove to be difficult to diagnose. We present the case of a 52-year-old female found to have a dedifferentiated GIST without prior imatinib mesylate therapy. This case is the first reported dedifferentiated GIST arising de novo from the small bowel, and at 30cm in greatest diameter, the largest reported to date. Additionally, we demonstrate for the first time the loss of DOG1 in the anaplastic component of the tumor. De novo dedifferentiated GIST is a rare and diagnostically challenging tumor that may be mischaracterized unless considered in the differential diagnosis.

Calcifying Fibrous Tumor of the Small Intestine Associated with Castleman-like Lymphadenopathy

Calcifying fibrous tumor is a rare mesenchymal tumor that most commonly presents in younger individuals. We report the case of a 25-year-old woman that presented with severe abdominal pain and a small bowel mass at the site of an ileocolic intussusception with associated mesenteric lymphadenopathy. Surgical resection was performed, and pathologic analysis revealed that the mass was a calcifying fibrous tumor associated with Castleman-like adenopathy. This case intends to support a possible association between these two entities.

Chlamydia trachomatis in a thin-prep Papanicolaou Test.

G Chlamydia trachomatis cervicitis is very common in the United States, with more than 650 000 cases of genital infection reported to the Centers for Disease Control and Prevention in 1999. Despite its prevalence, definitive diagnosis in routine Papanicolaou tests is difficult, because inflammatory changes and squamous metaplasia mimic the cytopathologic changes of chlamydial infection. Infection is usually best diagnosed by fluorescence immunomicroscopy or molecular techniques. Liquid-based cervical cytology yields slides with greater