CDK8 Expression in Extrauterine Leiomyosarcoma Correlates With Tumor Stage and Progression.

Mediator is a multiprotein complex that acts as a versatile transcription coactivator in eukaryotes. CDK8 kinase complex is a 4-protein subunit of the mediator complex that can act as a transcriptional repressor or coactivator, depending on the specific pathways involved. Although the role of MED12 exon 2 mutations is documented in the pathogenesis of uterine leiomyomas, its role in extrauterine smooth muscle tumorigenesis is less clear. Similarly, there is a paucity of data on the role of CDK8 in extrauterine smooth muscle tumorigenesis and progression. Our study correlates immunohistochemical expression of CDK8 and MED12 with clinical and pathologic parameters in extrauterine leiomyosarcomas. Immunohistochemical expression of CDK8 and MED12 in leiomyosarcomas was correlated with the tumor grade, stage, and the presence of local recurrence or metastasis. MED12 was expressed in the majority of leiomyosarcomas regardless of their stage or grade. CDK8 expression was lost in 1 of 6 pT1 tumors, compared with 9 of 10 pT2 tumors (P=0.0076). When the second group was expanded to include those tumors that did not have a recorded pathologic stage but had local recurrence and distant metastases, the difference in CDK8 expression was also statistically significant. Loss of CDK8 expression by immunohistochemistry is more prevalent in somatic leiomyosarcomas presenting at a higher histopathologic stage, as well as with local and distant recurrence, and can be used to enhance the current predictive parameters.

Ossifying fibromyxoid tumor: a study of 6 cases of atypical and malignant variants.

Ossifying fibromyxoid tumors (OFMT) of soft parts are rare, slow-growing tumors that have potential for local recurrence and may metastasize. While OFMT originally was considered benign, several cases of malignant OFMT have been documented. There is no universally accepted risk stratification, although this study emphasizes the importance of utilizing histology, immunohistochemistry and FISH in establishing the diagnosis. Herein, we describe six cases of atypical and malignant OFMT with differences in morphologic features, 5 of which display the proposed morphological criteria for malignancy. The patients were mostly male (M=5, F=1) with an age range of 33-69 years. The tumors arose from the extremities (3 cases), the shoulder (1 case), the head and neck area (1 case), and the paraspinal area (1 case). One tumor had high grade and overtly sarcomatous changes, while another invaded the underlying clavicle. Two cases showed cytological atypia and necrosis. Fluorescence in situ hybridization (FISH) detected rearrangement of the PHF1 gene in 5 cases. All cases were positive for EAAT4 and actin by immunohistochemistry, while negative for desmin. Three tumors were immunoreactive for S100 protein. INI-1 immunohistochemical staining was conserved in all but 2 cases in which a mosaic loss of expression was noted. All but two patients are currently alive and free of disease.

Human Immunodeficiency Virus-associated primary effusion lymphoma: An exceedingly rare entity in cerebrospinal fluid.

Primary effusion lymphoma (PEL) in patients with Human Immunodeficiency Virus (HIV) infection may involve pleural, pericardial, and peritoneal cavities. PEL involving the cerebrospinal fluid (CSF) is exceedingly rare, and to our knowledge has only been reported in two cases. We report another case of PEL diagnosed in CSF from a 61-year-old male with Acquired Immunodeficiency Syndrome that presented with neurological symptoms. Imaging studies of his brain showed leptomeningeal/periventricular enhancement, but no mass lesion. His CSF demonstrated human herpesvirus-8 positive pleomorphic lymphoplasmacytoid cells of null cell phenotype. This case highlights that albeit rare, PEL should be included in the differential diagnosis when large atypical cells are encountered in CSF of HIV-positive patients, even when such patients have no history of lymphoma. As in this case, ancillary studies are required to make an accurate diagnosis of PEL in CSF cytology.

Mucormycosis infection following intravenous access in the forearm.

Mucormycosis is an opportunistic infection that is often fatal, requiring aggressive local control as well as systemic therapy. A rare case of a forearm infection originating in a traumatic intravenous access portal is described in the present study. The Mucor species infection prevented liver transplant, and the patient passed away. In the present case, it was decided to limit the resection to the skin and subcutaneous tissue based on a frozen section and the viability of the biopsied tissue. With consistently rising numbers of immunocompromised patients, awareness and familiarity with mucormycosis in the extremities is important. Knowing that a minimal traumatic event may precede the infection could assist in prevention and early diagnosis. Guidelines for pathological and clinical diagnosis and treatment need to be further clarified.

Malignant granular cell tumor of the ulnar nerve with novel cytogenetic and molecular genetic findings.

We report an unusual case of ulnar nerve-based malignant granular cell tumor characterized by gains of chromosome 10 and loss of P16 detected by conventional karyotyping and by fluorescence in situ hybridization, respectively, in a 74-year-old male. To our knowledge, these findings have never been reported previously in malignant granular cell tumors.

Pathobiology of small invasive breast cancers without metastases (T1a/b, N0, M0): National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-21.

BACKGROUND: Uncertainties continue to exist concerning the outcomes and management of small (T1a/b N0 M0) invasive breast cancers. METHODS: A central pathology review was performed of 638 such lesions from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial B-21. RESULTS: Univariate analysis revealed a high risk for ipsilateral breast tumor recurrence with tumors exhibiting a ductal carcinoma in situ component or poor nuclear grade. The converse (protective effect) was found with tumors arising in radial scars, those of tubular histologic type, and those with moderate/marked tumor stroma. The correlations were generally similar for disease-free survival. However, only nuclear grade was found to be independently significant for both of these outcomes. Only lymphatic tumor extension was univariately and multivariately significant for overall survival. CONCLUSIONS: The long-term results of follow-up (median, 11.2 years) from the current trial continue to support the need for local breast irradiation and adjuvant therapy in the management of patients with these small cancers.