Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants.

AIMS: Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE. METHODS AND RESULTS: Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC. CONCLUSIONS: This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.

Pelvic Radiation-Induced Sarcoma With Rhabdomyoblastic Differentiation Following Treatment of Cervical Cancer.

Radiation-induced sarcomas (RIS) are a rare long-term complication of radiation therapy, with a reported incidence of 2.5-5.5%. They usually develop several years following exposure to radiotherapy. The most common reported subtypes are undifferentiated pleomorphic sarcoma, angiosarcoma, and leiomyosarcoma. Breast cancer is the most common primary malignancy preceding RIS, followed by uterine cervical carcinoma. Only a few cases of RIS with rhabdomyoblastic differentiation have been reported in the literature, usually following the treatment of retinoblastoma. Herein, we report a rare case of RIS with rhabdomyoblastic differentiation in the pelvic region developing 12 years after cervical cancer radiation therapy.

Appendiceal diverticulitis presenting as acute appendicitis diagnosed postoperatively.

Appendiceal diverticular disease is a rare entity. We report a case of appendiceal diverticulitis mimicking acute appendicitis and diagnosed postoperatively on histopathology. A 28-year-old female presented with a 2-day history of shifting periumbilical pain associated with nausea and anorexia. A computed tomography scan of the abdomen demonstrated acute appendicitis. She was taken to laparoscopic appendectomy. Histopathology showed appendiceal diverticulitis, and perforation of an inflamed diverticulum with periappendicitis. Diverticulosis of the appendix is classified as congenital and acquired. Diagnosis can be made preoperatively by imaging. In this case, diverticulosis was not radiologically evident, and was interpreted as acute appendicitis. Gross appearance of the resected appendix was not suggestive of diverticulitis. Other cases reported that the gross specimen had evidence of diverticular disease. Surgeons should be aware that inflamed appendixes may harbor different pathologies warranting further management.

Single-Cell Quantitative PCR: Advances and Potential in Cancer Diagnostics.

Tissues are heterogeneous in their components. If cells of interest are a minor population of collected tissue, it would be difficult to obtain genetic or genomic information of the interested cell population with conventional genomic DNA extraction from the collected tissue. Single-cell DNA analysis is important in the analysis of genetics of cell clonality, genetic anticipation, and single-cell DNA polymorphisms. Single-cell PCR using Single Cell Ampligrid/GeXP platform is described in this chapter.

Myeloproliferative Neoplasms With Calreticulin Mutations Exhibit Distinctive Morphologic Features.

OBJECTIVES: Calreticulin (CALR) mutations are present in 50% to 85% of JAK2/MPL wild-type (wt) myeloproliferative neoplasms (MPNs). The histopathologic features of CALR-mutated MPNs are unknown. METHODS: We identified 71 patients with essential thrombocythemia (ET), primary myelofibrosis (PMF), and post-essential thrombocythemia myelofibrosis (post-ET MF) with available CALR status. CALR was assessed using capillary electrophoresis followed by Sanger sequencing confirmation. CALR status was correlated with histopathologic features. RESULTS: The megakaryocytes of CALR-mutated PMF more often were hyperchromatic (20/21) compared with CALR-wt cases (10/14) (P = .05). CALR-mutated ET showed more megakaryocytic clustering (7/7) compared with CALR-wt cases (5/9) (P = 03). Megakaryocytes of CALR-mutated post-ET MF (8/8) had a predominance of convoluted nuclei compared with CALR-wt cases (2/4) (P = .03). CALR mutations were more frequent in post-ET MF compared with ET (P = .04). CONCLUSIONS: CALR-mutated MPNs have a higher frequency of megakaryocytic aberrancies compared with CALR-wt cases. Patients with CALR-mutated ET appear to be more likely to develop myelofibrosis compared with patients with wt CALRUpon completion of this activity you will be able to: describe morphologic features that are associated with CALR-mutated myeloproliferative neoplasms.examine cases of essential thrombocythemia and primary myelofibrosis and predict which cases are more likely to be CALR-mutated based on histopathologic features.initiate CALR mutation testing for cases likely to have mutations. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Exam is located at www.ascp.org/ajcpcme.