USP6 gene rearrangement in nodular fasciitis and histological mimics.

AIMS: Nodular fasciitis is known to be a benign mimic of sarcoma, both clinically and histologically. Accurate diagnosis, particularly on small biopsies, remains a challenge, as the morphology can be varied and the immunophenotype is essentially non-specific. Recently, rearrangement of the ubiquitin-specific protease 6 (USP6) gene has been reported as a recurrent and specific finding in nodular fasciitis. The aim of this this study was to evaluate the diagnostic utility of USP6 fluorescence in-situ hybridization (FISH) analysis in a subset of spindle-cell proliferations in which nodular fasciitis enters into the differential diagnosis. METHODS AND RESULTS: A database search was performed at the Middlemore Hospital Histopathology Department. All in-house cases diagnosed between 2002 and March 2014 in which nodular fasciitis was considered as a differential diagnosis were retrospectively identified. Twenty cases were retrieved, reviewed and categorized as 'definite', 'possible' or 'definitely not' nodular fasciitis by consensus morphological opinion of three experienced pathologists. FISH analysis for USP6 rearrangement was performed in each case, with a commercially available break-apart probe. Of seven cases that were morphologically categorized as 'definite' nodular fasciitis, six were FISH-positive and one was FISH-negative. Of four cases categorized as 'possible' nodular fasciitis, one was FISH-positive and three were FISH-negative. Nine cases categorized as 'definitely not' nodular fasciitis were all FISH-negative. In the morphologically definitive cases, FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of nodular fasciitis. The positive predictive value was 100%, and the negative predictive value 90%. CONCLUSIONS: USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration.

Primary Pseudomyogenic Hemangioendothelioma of Bone.

Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging.

Muir-Torre syndrome-associated pleomorphic liposarcoma arising in a previous radiation field.

Muir-Torre syndrome is a variant of Lynch syndrome, characterised by sebaceous neoplasia and/or keratoacanthomas associated with visceral malignancies. Muir-Torre syndrome is caused by germline mutations of one of the mismatch repair genes, frequently MSH2 and less frequently MLH1 and MSH6. Visceral malignancies associated with Muir-Torre syndrome and Lynch syndrome include colorectal, endometrial and other gastrointestinal, urological and gynaecological malignancies. Small numbers of Lynch syndrome-associated soft tissue sarcomas have been reported, but there are no reported cases of soft tissue sarcomas in Muir-Torre syndrome. In this study, we report a 74-year-old man with known Muir-Torre syndrome with confirmed MSH2 germline mutation, diagnosed with pleomorphic liposarcoma of the right buttock in a previous radiation field. The tumour showed loss of expression of MSH2 and MSH6 on immunohistochemistry. Immunohistochemistry on another pleomorphic liposarcoma in a different patient with no previous history of Muir-Torre syndrome or Lynch syndrome showed no loss of expression of mismatch repair proteins. This is the first report of Muir-Torre syndrome-associated sarcoma and the first case of post-radiation sarcoma in Lynch syndrome.

Microscopic Kaposiform hemangioendothelioma with extensive lymphangiomatosis: an extraordinary example of an unusual entity.

Kaposiform hemangioendothelioma (KHE) is presently classified as a vascular neoplasm of intermediate malignant potential. The clinical course of large, deep-seated tumors is frequently complicated by consumptive coagulopathy and life-threatening hemorrhage, while superficial tumors tend to behave in an indolent manner, with no known reports of distant metastasis. We describe an unusual example of KHE occurring as an incidental microscopic finding, within a background of extensive lymphangioma-like changes. The patient underwent 4 intralesional excisions over a period of 6 years, and the Kaposiform component accounts for less than 5% of the overall tissue excised. The patient remains clinically well with residual disease 5 years after conservative surgery, and there has been no evidence of regional or distant metastasis. Based on existing literature, it appears doubtful that KHE has any metastatic potential at all, which calls into question the appropriateness of its place in the spectrum of malignant vascular neoplasms.

Aggressive angiomyxoma [corrected] of the female genital tract and pelvis--clinicopathologic features with immunohistochemical analysis.

Aggressive angiomyxoma (AA) is a benign, slow-growing tumor that characteristically occurs in women of reproductive age. Local recurrence is cited in 30% to 40% of cases. Wide local excision is the treatment of choice. However, recent reports suggest a role for hormone manipulation in the management of these tumors. The morphology and immunophenotype of AA overlap with that of other, mainly benign vulvovaginal mesenchymal tumors. Diagnosis rests primarily on hematoxylin and eosin staining features, and distinction is important in determining appropriate treatment and follow-up. Rearrangement of HMGA2 has been shown in AA, and reports suggest that HMGA2 immunohistochemistry may have a role in the routine diagnosis of AA, its distinction from mimics, and in the evaluation of margins. Furthermore, CDK4 immunopositivity has been described in AA. We describe a series of 9 cases of AA with typical histology and long-term follow-up, and evaluate the role of HMGA2, CDK4, estrogen, and progesterone immunohistochemistry. One of 9 women (11%) experienced recurrence, with the second at 17 years, which is the longest recorded in the English literature. HMGA2 immunohistochemistry was positive in 37.5% of cases, consistent with the reported frequency of HMGA2 gene rearrangement, and negative in all benign mimics. CDK4 immunoreactivity was weak, diagnostically not helpful, and of uncertain significance. Immunohistochemistry for estrogen and progesterone were positive in 87.5% of AAs, and were widely positive in control groups.

Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome and metastases following pregnancy.

BACKGROUND: The most frequent molecular abnormality observed in dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring chromosome or translocation resulting in fusion of the gene encoding the alpha-chain of type 1 collagen, COL1A1 from 17q22, to the platelet-derived growth factor beta-chain, PDGFB gene from 22q13. Rare cases documenting variant ring or marker chromosomes involving regions other than 17q22 and 22q13 have been reported. Further analysis in three of these cases demonstrated the presence of the COL1A1 and PDGFB genes. METHODS: We report a further case of DFSP with a rare variant ring chromosome. The tumor appeared to undergo accelerated growth during pregnancy, then metastasized following pregnancy. We describe the clinical, histological, immunohistochemical, and cytogenetic features. RESULTS: The metastatic tumor showed a variant r(17;?) chromosome. A locus-specific probe was required to demonstrate presence of the PDGFB gene within the ring, indicating cryptic molecular rearrangement between chromosomes 17 and 22, and recombination with an unknown chromosome. CONCLUSIONS: Cryptic rearrangement of chromosomes 17 and 22 should be suspected in variant ring chromosomes and translocations. Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical resection should be avoided.