Nicole D. Riddle

Angiosarcoma Arising in Chronic Expanding Hematoma: Five Cases of an Underrecognized Association.

Little is known about the etiology or pathogenesis of angiosarcoma (AS). We describe a series of 5 cases of AS arising in chronic expanding hematomas. Inclusion criteria were the presence of a hematoma of at least 1-year duration and a thick fibrous wall surrounding the hematoma. Patients were 4 men and 1 woman; ages ranged from 43 to 71 years. Locations were the thigh (3), chest wall (1), and pelvic soft tissue involving the ischial bone (1). Hematoma duration ranged from 2 to 25 years. All cases had large cystic hematomas >10 cm; 2 had prior radiation. Thick fibrous walls surrounded the hematomas, with foci of hemosiderin and foamy histiocytes. Wall thickness ranged from 0.2 to 1.0 cm and varied within lesions. All AS were epithelioid, and in 3 cases the tumor invaded through the cyst wall. Immunoreactive nuclear c-myc was noted in 3/3 cases available for testing. Follow-up disclosed 4 patients developed metastatic disease, 3 of whom died of disease, 4, 8, and 15 months after diagnosis; the fourth patient is alive without disease after chemotherapy at 59 months. One patient without metastases is alive without disease 18 months after diagnosis; this tumor was confined to the cyst without penetration through the wall. We identified 4 similar cases in the literature, 3 as individual case reports (all epithelioid AS), and 1 as part of a series of AS. To our knowledge, this is the first series of AS arising in chronic expanding hematomas. Recognition of this unusual complication should alert clinicians to provide periodic clinical follow-up to these patients and to biopsy any case with sudden or uncontrolled enlargement. We recommend that excised chronic hematomas be well sampled histologically to search for AS and, if identified, to determine its extent and invasiveness.

Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation

Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1. The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities. SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor. In addition, numerous benign tissues were tested for SIRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, smooth muscle, and striated muscle. A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76.5%), and rhabdomyosarcoma (87%). The other lesions examined were negative. Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry. Furthermore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy. Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms.

Clinical and Pathologic Features of Hispanic Endometrial Cancer Patients with Loss of Mismatch Repair Expression

Objectives Approximately 3% to 5% of endometrial cancers (EC) are associated with Lynch syndrome (LS). The clinical characteristics and prevalence of LS have not been well studied in the US Hispanic population. Hispanics are the largest and fastest growing ethnic minority group in the United States. We sought to characterize the demographics, tumor characteristics, and prevalence of loss of mismatch repair (MMR) protein expression in a large Hispanic population with EC. Methods From January 1, 2005, to August 1, 2012, 83 women of Hispanic ethnicity diagnosed with EC 50 years and younger were identified. Clinical and pathologic data were abstracted from the electronic medical record. Tumor studies included immunohistochemistry of MLH1, MSH2, MSH6, and PMS2 and methylation of the MLH1 promoter. Results Ninety-five percent of patients were overweight or obese. The mean body mass index was 40.1 kg/m2, 75% had irregular menses, 36% had diabetes, 46% were nulliparous, and 95% had endometrioid histology. Thirteen patients (15.7%) had tumor MMR deficiency due to a presumed germline mutation (9 MSH6, 3 MSH2, and 1 MLH1). The pattern of MMR protein loss was consistent with the expected binding properties of the MMR heterodimer complexes. No significant difference was found in clinical or pathological variables between patients with and without MMR deficient tumors. Conclusions The prevalence of molecular findings consistent with LS was at least as high as other populations of varied geography, race, and ethnicity. We found no reliable factors to include body mass index, family history, synchronous tumors, or pathologic tumor features to serve as triage markers for which ECs should be screened for MMR protein loss. Our findings support a recommendation for universal screening of ECs utilizing 2-antibody testing with MLH1 promoter methylation testing as indicated up to 60 years or older. Our recommendations should be generalizable to other Hispanic populations in the Southern United States.

MITF (microphthalmia-associated transcription factor)

Review on MITF (microphthalmia-associated transcription factor), with data on DNA, on the protein encoded, and where the gene is implicated.