Lymphatic-type "Angiosarcoma" With Prominent Lymphocytic Infiltrate.

We report 21 cases of a distinctive and unique vascular tumor which we propose to be a pure lymphatic-type angiosarcoma characterized by architectural and growth characteristics of angiosarcoma, cytologic, and immunohistochemical features of lymphatic differentiation, a prominent lymphocytic infiltrate, and variable nuclear grade. Patients included 12 males and 9 females with a median age of 65 years (range: 32 to 95 y). Tumors involved the head and neck (n=11), lower extremities (n=5), trunk (n=4), and upper extremity (n=1) and were located superficially in the dermis and/or subcutis.

Intrasinusoidal Spread of Hepatic Epithelioid Hemangioendothelioma: Implications for the Diagnosis in Minimal Samples.

Epithelioid hemangioendothelioma (EHE) is an angiocentric tumor that, when arising in liver, is centered around hepatic/portal veins. However, EHE cells can also track along sinusoids, which is not well recognized or studied. We identified 18 cases of hepatic EHE and 6 nonhepatic EHEs.

Histiocyte-rich rhabdomyoblastic tumor: rhabdomyosarcoma, rhabdomyoma, or rhabdomyoblastic tumor of uncertain malignant potential? A histologically distinctive rhabdomyoblastic tumor in search of a place in the classification of skeletal muscle neoplasms.

Skeletal muscle tumors are traditionally classified as rhabdomyoma or rhabdomyosarcoma. We have identified an unusual adult rhabdomyoblastic tumor not clearly corresponding to a previously described variant of rhabdomyoma or rhabdomyosarcoma, characterized by a very striking proliferation of non-neoplastic histiocytes, obscuring the underlying tumor. Ten cases were identified in nine males and one female with a median age of 43 years (range 23-69 years).

Fibrous hamartoma of infancy: a clinicopathologic study of 145 cases, including 2 with sarcomatous features.

Fibrous hamartoma of infancy is a rare soft tissue lesion of infants and young children with characteristic triphasic morphology, which typically occurs in the axilla and less commonly in other locations. We reviewed 145 cases of fibrous hamartoma of infancy from our consultation archives. Cases occurred in 106 males and 39 females (mean age-15 months; range-birth to 14 years), and involved both typical sites (eg, axilla/back/upper arm) (n=69) and unusual locations (n=76).

MDM2 and CDK4 Immunohistochemistry: Should It Be Used in Problematic Differentiated Lipomatous Tumors?: A New Perspective.

Although most cases of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) can be diagnosed solely on the basis of histologic features, those lacking diagnostic histologic features require ancillary studies for accurate classification. Fluorescent in situ hybridization (FISH) for amplification of MDM2 has been considered the gold standard for diagnosis in these situations. Immunostaining for MDM2 and/or CDK4 has been adopted as a surrogate method because of its high concordance rate with FISH and lower cost.

Physician scientist research pathway leading to certification by the American Board of Pathology.

In 2014, the American Board of Pathology, in response to the pathology community, approved a physician scientist research pathway (PSRP). This brief report summarizes the history of and objectives for creating the physician scientist research pathway and the requirements of the American Board of Pathology for the certification of physician scientist research pathway trainees.

TGFBR3 and MGEA5 rearrangements are much more common in "hybrid" hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma that most often involves the distal extremities of adults. Some MIFSs have been reported to show TGFBR3 and MGEA5 rearrangements. TGFBR3 and MGEA5 rearrangements have also been reported in hemosiderotic fibrolipomatous tumor (HFLT), in pleomorphic hyalinizing angiectatic tumor (PHAT), and in rare tumors allegedly showing features of both HFLT and MIFS (hybrid HFLT-MIFS).

Physician Scientist Research Pathway Leading to Certification by the American Board of Pathology.

In 2014, the American Board of Pathology, in response to the pathology community, approved a physician scientist research pathway. This brief report summarizes the history of and objectives for creating the physician scientist research pathway and the requirements of the American Board of Pathology for the certification of physician scientist research pathway trainees.

Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y).

MDM2 Amplification in Problematic Lipomatous Tumors: Analysis of FISH Testing Criteria.

To discriminate lipomas from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) we perform fluorescence in situ hybridization (FISH) for MDM2 amplification in several problematic situations: "lipomas" >10 cm, lesions with equivocal atypia, recurrent "lipomas," all retroperitoneal/pelvic/abdominal "lipomas", and in cases not fitting the above criteria but having worrisome clinical or radiologic features. To ascertain the validity of these criteria, we have reviewed our experience with 301 consecutive differentiated lipomatous tumors in which the diagnosis of ALT could not be established on the basis of histologic sections and in which FISH was performed on the basis of the above criteria. The final diagnosis was based on MDM2 amplification status.

Myofibromas with atypical features: expanding the morphologic spectrum of a benign entity.

Typical myofibromas are biphasic tumors composed of a central zone of immature spindled to rounded cells arranged in a pericytic pattern and a peripheral zone of myoid nodules. Central necrosis is occasionally seen. A small but undefined subset of myofibromas displays atypical features that may lead to a misdiagnosis of sarcoma.

The General Surgeon's quandary: atypical lipomatous tumor vs lipoma, who needs a surgical oncologist?

Background: Differentiating large lipomas from atypical lipomatous tumors (ALT) is challenging, and preoperative management guidelines are not well defined. The diagnostic ambiguity leads many surgeons to refer all patients with large lipomatous masses to an oncologic specialist, perhaps unnecessarily.

Study Design: In this retrospective cohort study of patients with nonretroperitoneal lipomatous tumors, preoperative characteristics discernible without invasive diagnostic procedures were evaluated for diagnostic predictive value.

Superficial CD34-positive fibroblastic tumor: report of 18 cases of a distinctive low-grade mesenchymal neoplasm of intermediate (borderline) malignancy.

Fibroblastic mesenchymal tumors show a spectrum of biological behavior, from benign to fully malignant. We report our experience of two decades with a distinctive, previously undescribed low-grade fibroblastic tumor of the superficial soft tissues. Eighteen cases were identified within our consultation files, previously coded as 'low-grade sarcoma, not further classified' and 'malignant fibrous histiocytoma, low grade'.

PHF1 rearrangements in ossifying fibromyxoid tumors of soft parts: A fluorescence in situ hybridization study of 41 cases with emphasis on the malignant variant.

Ossifying fibromyxoid tumor of soft parts (OFMT) is a rare soft tissue neoplasm of uncertain differentiation. Very recently recurrent rearrangements of the PHF1 gene have been reported in OFMT, including typical, atypical, and malignant variants. We sought to validate and extend these findings in a larger series of well-characterized OFMT, in particular malignant variants.

Fibrosarcoma-like lipomatous neoplasm: a reappraisal of so-called spindle cell liposarcoma defining a unique lipomatous tumor unrelated to other liposarcomas.

The term "spindle cell liposarcoma" has been applied to liposarcomas (LPSs) composed predominantly or exclusively of spindled cells. These tumors have been considered variants of well-differentiated LPS (WDL), myxoid LPS, and spindle cell lipoma, suggesting that this is a heterogenous group of lesions. Using strict morphologic criteria and molecular and immunohistochemical analyses, we have identified a homogenous group of spindle cell lipomatous tumors, histologically and genetically distinct from other forms of LPS, which we have called "fibrosarcoma-like lipomatous neoplasm.

Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of 29 cases with evaluation of MDM2 gene amplification in 26.

Pleomorphic liposarcoma (PL) is an uncommon form of liposarcoma that rarely occurs in the skin and subcutis. As its behavior in this setting is incompletely characterized, we undertook a study of a series of superficial PLs, defined as those arising or based primarily in the dermis and/or subcutis without involvement of deep structures. In addition, MDM2 gene amplification, a diagnostic signature of well-differentiated/dedifferentiated liposarcoma (WDL/DL), was evaluated to address the recent observation that this gene is amplified within PL-like areas in DL.

Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma.

Integrating transcriptomic sequencing with conventional cytogenetics, we identified WWTR1 (WW domain-containing transcription regulator 1) (3q25) and CAMTA1 (calmodulin-binding transcription activator 1) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal translocation that is characteristic of epithelioid hemangioendothelioma (EHE), a vascular sarcoma. This WWTR1/CAMTA1 gene fusion is under the transcriptional control of the WWTR1 promoter and encodes a putative chimeric transcription factor that joins the amino terminus of WWTR1, a protein that is highly expressed in endothelial cells, in-frame to the carboxyl terminus of CAMTA1, a protein that is normally expressed only in brain. Thus, CAMTA1 expression is activated inappropriately through a promoter-switch mechanism.

Anatomic tumor location influences the success of contemporary limb-sparing surgery and radiation among adults with soft tissue sarcomas of the extremities.

Purpose: To examine the influence of anatomic location in the upper extremity (UE) vs. lower extremity (LE) on the presentation and outcomes of adult soft tissue sarcomas (STS).

Methods And Materials: From 2001 to 2008, 118 patients underwent limb-sparing surgery (LSS) and external beam radiotherapy (RT) with curative intent for nonrecurrent extremity STS.

Pediatric cutaneous angiosarcomas: a clinicopathologic study of 10 cases.

Cutaneous angiosarcomas are rare tumors, which predominantly arise in the sun-exposed skin of the head and neck of adult and elderly patients. Rarely, these tumors can be seen in children. We identified cutaneous angiosarcomas in 10 children and assessed clinical (patient age, tumor site, tumor size, and tumor focality) and histologic features including growth pattern (vasoformative vs.

Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors.

A distinctive subset of PEComas harbors TFE3 gene fusions.

Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor, lymphangioleiomyomatosis, and less common neoplasms of soft tissue, gynecologic, and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 100% of PEComas; however, TFE3 gene status in these neoplasms has not been systematically investigated. We used a fluorescence in situ hybridization (FISH) break-apart assay to evaluate for evidence of TFE3 gene fusions in archival material from 29 PEComas.

Liposarcomas with mixed well-differentiated and pleomorphic features: a clinicopathologic study of 12 cases.

Pleomorphic liposarcoma (PL) is an undifferentiated pleomorphic sarcoma containing pleomorphic lipoblasts. PL almost always arises de novo without an associated low-grade precursor lesion [eg, well-differentiated liposarcoma (WDL)]. We have, however, observed rare cases of PL, which arose in association with WDL and have studied these cases to define their clinicopathologic features and their nosologic relationship to other forms of liposarcoma.