Michael Michal

Abstract We herein present an overview of the upcoming 5 th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial, mesenchymal, and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for (mammary analog) secretory carcinoma, and has not been documented in any other salivary tumor type. The present study comprised a clinical, histologic, and molecular analysis of 10 cases of secretory carcinoma, with typical morphology and immunoprofile harboring a novel ETV6-RET translocation.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm of uncertain histogenesis that has been linked to tumor-induced osteomalacia (TIO) since 1959. The neoplastic cells produce increased amount of FGF23 which results in TIO via uncontrolled renal loss of phosphate (phosphaturia), and consequently diminished bone mineralization. To date, ∼300 cases have been reported. Although there is increasing evidence that PMT can be diagnosed by reproducible histopathologic features, firm diagnosis has been often restricted to cases associated with TIO and, hence, diagnosis of "nonphosphaturic variants" remained challenging. Recently, FGFR1/FN1 gene fusions were detected in roughly half of cases. We herein reviewed the clinicopathologic features of 22 PMTs (15 cases not published before), stained them with an extended immunohistochemical marker panel and examined them by fluorescence in situ hybridization for FGFR1 gene fusions. Patients were 12 males and 9 females (one of unknown sex) aged 33 to 83 years (median: 52 y). Lesions affected the soft tissues (n=11), bones (n=6), sinonasal tract (n=4), and unspecified site (n=1). Most lesions originated in the extremities (9 in the lower and 4 in the upper extremities). Acral sites were involved in 10 patients (6 foot/heel, 3 fingers/hands, and 1 in unspecified digit). Phosphaturia and TIO were recorded in 10/11 and 9/14 patients with detailed clinical data, respectively. Limited follow-up (5 mo to 14 y; median: 16 mo) was available for 14 patients. Local recurrence was noted in one patient and metastasis in another patient. Histologically, 11 tumors were purely of conventional mixed connective tissue type, 3 were chondromyxoid fibroma-like, 2 were hemangio-/glomangiopericytoma-like with giant cells, and 1 case each angiomyolipoma-like and reparative giant cell granuloma-like. Four tumors contained admixture of patterns (predominantly cellular with variable conventional component). Immunohistochemistry showed consistent expression of CD56 (11/11; 100%), ERG (19/21; 90%), SATB2 (19/21; 90%), and somatostatin receptor 2A (15/19; 79%), while other markers tested negative: DOG1 (0/17), beta-catenin (0/14), S100 protein (0/14), and STAT6 (0/7). FGFR1 fluorescence in situ hybridization was positive in 8/17 (47%) evaluable cases. These results add to the phenotypic delineation of PMT reporting for the first time consistent expression of SATB2 and excluding any phenotypic overlap with solitary fibrous tumor or sinonasal glomangiopericytoma. The unifying immunophenotype of the neoplastic cells irrespective of the histologic pattern suggests a specific disease entity with diverse morphotypes/variants rather than different neoplasms unified by TIO.