Pennie J. Symmans

Diabetic muscle infarction in patients on dialysis.

Spontaneous muscle infarction in diabetic patients is a rare condition that usually occurs in those with advanced diabetic complications. There is a high prevalence of diabetic nephropathy and varying degrees of renal failure. Both type 1 and type 2 diabetics are at risk. The mean age at presentation is approximately 40 years, and both sexes are affected. The cause is uncertain but appears to be attributable to diabetic microangiopathy, with thickening of walls of small arteries and fibrinoid occlusion. There is necrosis of all elements of the muscle, with polymorphonuclear or mononuclear cellular infiltration and a varying but often limited degree of regeneration, depending on the age of the lesion. The presentation is usually acute, with pain and swelling localized to the thigh in most instances. Systemic signs such as pyrexia are infrequent. Laboratory tests (such as white cell count and creatinine kinase) and plain radiographs are not helpful, although the erythrocyte sedimentation rate is often elevated. The diagnosis, in the appropriate setting, is strongly suggested by magnetic resonance imaging, which shows increased signal intensity and asymmetry of the muscle on T2-weighted scanning as well as fluid in the tissue planes. Management consists of resting the muscle, analgesics, and gradual mobilization. Recurrence is common and may be seen in more than 50% of the patients.

USP6 gene rearrangement in nodular fasciitis and histological mimics.

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.

Benign Proliferative Nipple Duct Lesions Frequently Contain Cam 5.2 and Anti-cytokeratin 7 Immunoreactive Cells in the Overlying Epidermis

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with skin changes typically present in Pagets disease of the nipple. The identification of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Pagets disease. We studied the nipple epidermis in nine cases of PNDL and compared them with 26 histologically normal nipples from mastectomy specimens. CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytokeratin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven cases, these epidermal immunoreactive cells showed continuity with the underlying PNDL, suggesting the spread or continuation of lesional cells to the epidermis. Dispersed single immunoreactive cells were identified in small numbers (scattered) in the basal layer of the epidermis in 12 of 26 normal nipples and more frequently in 1 of 12 cases. In all cases, the intraepidermal cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 and anti-CK7 immunoreactive cells, which are normally present in the nipple epidermis, may proliferate and form aggregates when there is an underlying PNDL. The presence of these cells does not imply Pagets disease when the intraepidermal cells have a bland cytologic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.

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 α‐chain of type 1 collagen, COL1A1 from 17q22, to the platelet‐derived growth factor β‐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.

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.

Interstitial fluid and hypoechoic wall: two sonographic signs of breast abscess.

Many mammographic and sonographic features of breast abscess overlap with those of carcinoma. We reviewed the usefulness of interstitial fluid and hypoechoic walls in the sonographic diagnosis of breast abscess.

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.

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.

53. USP6 gene rearrangement in nodular fasciitis

Background: Nodular fasciitis (NF) is a self-limiting soft tissue lesion which can mimic sarcomas and cause diagnostic challenges, particularly as its morphology can be varied and the immunohistochemical profile is generally non-specific. Recently, USP6 gene rearrangement has been identified as a recurrent and specific feature in NF. If this is a consistent finding, testing for this gene rearrangement has the potential to be highly useful in morphologically challenging cases where NF features in the differential diagnosis. Aim: To determine the utility of USP6 gene arrangement analysis in NF and potential histological mimics. Method: A database search was performed at the Middlemore Histopathology Department. All in-house cases diagnosed between 2002 and March 2014, in which NF was considered as part of the differential diagnosis, were retrospectively identified. Twenty cases were retrieved, reviewed and categorised as ‘definite’, ‘possible’ or ‘definitely not’ NF by consensus morphologic opinions of three pathologists. Assessment for USP6 gene rearrangement was performed by fluorescence in situ hybridization (FISH) in each case, using a commercial break-apart probe. Results: Out of seven cases considered ‘definite NF’, six were positive for USP6 rearrangement and one was negative. Of four considered ‘possible NF’, one was FISH positive and three were negative. Nine cases categorized as ‘definitely not NF’ were all FISH negative. In the morphologically definitive cases, USP6 FISH has a sensitivity of 86% (6/7) and specificity of 100% (9/9). The positive predictive value is 100% (6/6) and the negative predictive value is 90% (9/10). Conclusion: USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration.