Sclerosing epithelioid mesenchymal neoplasm of the pancreas - a proposed new entity.

We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26-75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8-94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3-5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of "sclerosing epithelioid mesenchymal neoplasm" of the pancreas.

Acute myeloid leukemia following solid organ transplantation: case report and comprehensive review.

Organ transplant recipients are at an increased risk for subsequent malignancies including hematologic malignancies. The development of acute myeloid leukemia (AML) after solid organ transplantation is a rare but well-documented event. It is thought to be a consequence of immune dysregulation secondary to the use of immunosuppressive agents. Herein, we present the management of a liver transplantation recipient who presented with AML and comprehensively review the relevant literature. A 59-year-old male patient presented with fever and cough eight years after an orthotopic liver transplantation for cirrhosis and hepatocellular carcinoma. He received methylprednisolone and mycofenolate mofetil (MMF) followed by tacrolimus and rapamycin as immunosuppression. Upon admission to our hospital, his peripheral blood demonstrated 34% blasts and pancytopenia. A bone marrow biopsy confirmed the diagnosis of myelodysplastic syndrome (MDS) in transformation to AML. He was treated with induction chemotherapy and his sirolimus was continued but he expired four weeks after from refractory disease. No specific guidelines exist for the treatment of AML in solid organ transplant recipients. Treatment should be individualized and concurrent use of chemotherapeutic and immunosuppressive agents should be carefully balanced.

Collagenous gastroduodenitis.

Collagenous gastroduodenitis is a rare histopathologic entity characterized by marked subepithelial collagen deposition with associated mucosal inflammatory infiltrate. Only 4 cases have been reported, of which 3 had associated collagenous colitis. Collagenous gastroduodenitis without colonic involvement is exceptionally rare with only 1 case reported so far in the literature. We present a case of a 68-year-old woman with dyspepsia and mild anemia, who was found to have nodular gastric and duodenal mucosa on endoscopic examination. Histopathology showed collagenous gastroduodenitis. To the best of our knowledge, this is the second (and first in English literature) reported case of isolated collagenous gastroduodenitis.

Undifferentiated intimal sarcoma of large systemic blood vessels: report of 14 cases with immunohistochemical profile and review of the literature.

Intimal sarcoma (IS) is defined as a malignant tumor arising in the tunica intima of large blood vessels. In systemic circulation, the majority of IS develop in the aorta, where close to three fourths of published cases lack specific differentiation and are called undifferentiated intimal sarcomas (UIS). The remaining cases are intima-associated sarcomas of recognized types, also called differentiated intimal sarcomas (DIS). In this report, we further characterize UIS, including its immunohistochemical profile and results of comparative genomic hybridization. A total of 14 cases of UIS were collected from 17 medical institutions, including slides, blocks, electron photomicrographs, clinical abstracts, and reports of surgical pathology specimens and autopsies. The patients, 7 women and 7 men, were 41 to 85 years of age (median, 65.6 years). Twelve tumors arose from the aorta, one from the left external iliac and femoral arteries, and one in a large systemic vein (the venous tumor was included due to histologic similarity with the arterial lesions). Tumors ranged from 1 cm to over 10 cm in diameter. Histopathology was that of a largely necrotic, poorly differentiated epithelioid and pleomorphic malignant neoplasm relating to the tunica intima. Usually there was only a thin layer of viable tumor cells overlying a large thrombus. All tumors stained at least focally with the endothelial markers CD31 and Fli-1; however, there was otherwise considerable variability in immunophenotype. The distinctive histopathologic appearance of the primary luminal lesion was lost whenever tumor invaded outside the vessel wall (into adventitia and beyond) or in metastatic sites. Such extravascular tumors assumed a variety of patterns reminiscent of undifferentiated pleomorphic sarcoma (UPS; in older literature also known as pleomorphic malignant fibrous histiocytoma, MFH) or other distinct types of sarcomas, including osteosarcoma, angiosarcoma, and rhabdomyosarcoma. The results of comparative genomic hybridization were nonspecific. Eleven patients died of the disease, in an average of 11 months after diagnosis. Three patients are still alive and free of disease at 4, 16, and 27 years. UIS of large systemic vessels represents a distinct clinical entity where intraluminal sarcoma presents with thrombosis and occlusion of large vessels. It is associated with a highly characteristic, although not entirely specific, histology and immunohistochemical phenotype. The histogenesis of UIS is not certain; however, it seems that the cell of origin must leave the confines of the vessel wall to show altered morphology. Although there are rare long-term survivors, UIS behaves as a fully malignant neoplasm that is almost uniformly associated with metastases and tumor-related death.

Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progression.

PURPOSE: Membrane type 1 matrix metalloproteinase is a membrane-associated matrix metalloproteinase central to the degradation of basement membrane components via the activation of matrix metalloproteinase-2. Although membrane type 1 matrix metalloproteinase is overexpressed in invasive colon cancer, its expression in colonic polyps and carcinoma in situ has not been defined. In addition, the association of membrane type 1 matrix metalloproteinase expression by a primary tumor and recurrence of colon cancers has not been examined. METHODS: Immunoperoxidase staining was performed on randomly selected specimens containing adenoma (n = 17), carcinoma in situ (n = 9), or metastatic colon carcinoma (n = 8) with mouse monoclonal antibody to human membrane type 1 matrix metalloproteinase. Similar staining was also performed on randomly selected node-negative colon cancers that recurred within five years of resection (n = 17), matched for age, gender, stage, grade, and vascular, lymphatic, and perineural invasion, and node-negative colon cancers that did not recur within five years of resection (n = 17). Staining for membrane type 1 matrix metalloproteinase was graded. Mean scores for the groups were compared by Wilcoxon test. RESULTS: We found a progressive and significant increase in the mean score of membrane type 1 matrix metalloproteinase from normal mucosa to adenoma (P < 0.001), carcinoma in situ (P < 0.006), and invasive cancer (P < 0.009). However, there was no difference in membrane type 1 matrix metalloproteinase expression between the recurrent and nonrecurrent groups of node-negative colon cancer (P = not significant). CONCLUSIONS: These data suggest that membrane type 1 matrix metalloproteinase expression increases with progression from normal mucosa to invasive adenocarcinoma; however, it cannot be used as a prognostic indicator on which adjuvant therapy is based in node-negative colon cancer because of its failure to predict recurrence in this patient group.

Wilms' tumor in adults: aspiration cytology and cytogenetics.

The fine-needle aspiration cytologic findings of Wilms' tumor occurring in a 20-yr-old female patient and a 35-yr-old male patient showing blastemal, spindled sarcomatous and rare epithelial components are reported. The male patient had the typical presentation of renal mass with metastasis to lung and pleura, whereas the female patient had an unusual presentation with the tumor originated from the subcapsular nephrogenic zone of the kidney, extending into the liver without invasion into the renal cortex. Cytogenetic analysis of this case identified: 90, XXXX, +2x3-4, -5, -15, -16, -17, -17, i (17)(q10) x2. This finding may represent a genetic change associated with Wilms' tumor of older pediatric and young adult patients. To the best of our knowledge, this case is the sixth case with cytogenetic study and the first case revealing isochromosome 17q of an adult Wilms' tumor.