Purpose: Two SCF Skp2 ubiquitin ligase^related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in posttranscriptional degradation of p27Kip1 tumor suppressor. We analyzed the prognostic utility of p27Kip1 and its interacting cell cycle regulators in myxofibrosarcomas. Experimental Design: Clinicopathologic features and tissue microarray^based immunohistochemical expression of p27 Kip1 , Skp2, Cks1, cyclin E, cyclin A, Ki-67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and the relationship between Skp2 and p27 Kip1 proteins were examined in six cases by semiquantitative reverse transcription-PCR and Western blotting, respectively. Results: High indices of Skp2 (z10%), cyclin A (z10%), and Mcm2 (z50%) were adverse prognosticators at the univariate level. Furthermore, co-overexpression of Skp2 and cyclin A identified highly lethal cases in the entire cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall survival (OS)] and the lower-grade subset (Fe¤ de¤ ration Nationale des Centres de Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In multivariate analyses, Skp2 overexpression overshadowed most intrinsic clinicopathologic factors and independently correlated with worse metastasis-free survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive margins independently predicted inferior local recurrence-free survival (P = 0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation of Skp2 mRNA in four cases and Western blotting displayed a matched expression pattern of Skp2. Conclusions: Margin status and intrinsic property of myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly representative of the biological aggressiveness of myxofibrosarcomas and plays an important prognostic role.
Malignant eccrine spiradenoma is an extremely rare sweat gland tumor. It may develop de novo or arise in pre-existing benign eccrine spiradenoma. However, most tumors are presented in the latter mode. The case of a 50-year-old man with malignant transformation from previously existing benign eccrine spiradenoma over his right lateral thigh is reported. Evidence for this diagnosis includes two distinct morphological components. One is the well demarcated, small round to oval benign eccrine spiradenoma and the other is the malignant element with sarcomatoid differentiation. Some foci of transition between the benign eccrine spiradenoma and the sarcomatoid part are evident and represents that the latter may arise from the former. Whether different morphological patterns influence the patients' outcome is still doubtful. However, the malignant eccrine spiradenoma is thought to have the capacity of metastasis and lethal potentiality.
Malacoplakia is a chronic xanthogranulomatous inflammation that most commonly affects the urinary tract and the gastrointestinal system of middle-aged women. It is rarely encountered in a female genital tract, and only a handful of cases of malacoplakia of the ovary have been described. We report an unusual case of malacoplakia extensively involving the ovary, fallopian tube and uterus of a 47-year-old woman with poorly controlled diabetes mellitus. Escherichia coli was cultured from the ovarian lesion. To our knowledge, such an extensive female genital malacoplakia associated with diabetes mellitus has not been reported before. Widespread or atypical site malacoplakia occurring in a patient with systemic disease may result from a diminution of macrophagocytic function, either under the influence of the systemic illness or related to corticosteroid excess. We propose that diabetes mellitus without appropriate medical control may have resulted in impaired leukocyte function which, when combined with E. coli infection, led to the development of extensive malacoplakia in the genital tract of this patient.
Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease–related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.
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