ALK rearrangement in specific subtypes of lung adenocarcinoma: immunophenotypic and morphological features.

Lung adenocarcinomas are characterized by a variety of genetic and epigenetic changes that lead to activation of specific signaling pathways. This allowed the classification of lung adenocarcinomas according to genetic alterations and the clinical development of novel anticancer agents that affect the activity of specific oncoproteins. In such a context, chromosomal rearrangements that cause constitutive activation of ALK gene define a category of lung adenocarcinomas that is amenable to targeted therapy with ALK inhibitors. Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping. ALK status was determined, by immunohistochemistry and fluorescence in situ hybridization, in 94 surgically resected lung adenocarcinomas and correlated with histomorphological parameters. Indeed, ALK rearrangement was observed in 10/94 (11%) lung adenocarcinomas and enriched in tumors with a predominant mucinous (46%; p < 0.05) and solid (29%; p < 0.05) pattern. By contrast, it was lacking or sporadically observed in lung adenocarcinomas with predominant acinar, papillary or lepidic pattern. Moreover, the presence of signet-ring cells was predominantly observed in ALK-rearranged tumors (47%; p < 0.05). These data suggest that ALK rearrangement is associated with specific and distinct clinical-pathological characters compared to other genotypes. Thus, the knowledge of these characteristics can improve the diagnostic accuracy and lead to a better understanding of the behavior of ALK-rearranged NSCLC.

An urologic face of chronic lymphocytic leukemia: sequential prostatic and penis localization.

We report a patient with chronic lymphocytic leukemia (CLL) in whom a leukemic involvement of prostate and penis occurred in the advanced phase of his disease. Obstructive urinary symptoms were indicative of prostatic CLL infiltration, followed by the occurrence of an ulcerative lesion on the glans. Histologic examination confirmed the neoplastic B-cell infiltration. Both localizations responded to conventional treatments. A review of the literature confirms that leukemic involvement of the genito-urinary system is uncommon in CLL patients. However, it should be considered in CLL patients with urologic symptoms and a long history of the disease.

Mast cell sarcoma of the scalp: the first sign of undisclosed systemic mastocytosis?

Mastocytosis is a neoplastic disease of mast cells and their CD34+ precursors, including a heterogeneous group of disorders. It is characterized by abnormal growth and accumulation of mast cells in one or more organ systems. Mast cell sarcoma is an extremely rare and aggressive disease characterized by local proliferation of atypical mast cells, destructive growth and poor prognosis, without systemic involvement. Very few clinical cases describing this entity have been reported in the literature. In this paper, we report a case of a mast cell sarcoma, localized in the scalp of a 63-year-old woman; it appears to be the first manifestation of undisclosed systemic mastocytosis.

Dedifferentiated endometrioid adenocarcinoma of the uterus: a clinicopathologic study of a case.

Dedifferentiation confers more aggressive malignant behaviour than would be otherwise shown by the original tumor if present alone. This phenomenon has been described in several tumors, both mesenchymal and epithelial. Dedifferentiated endometrioid carcinoma either ovarian or endometrial is the latest addition to this family of tumors. Only 2 papers have appeared in the literature so far on the topic of dedifferentiated endometrioid carcinoma, both from the same institution. We report herein a case of endometrial dedifferentiated endometrioid carcinoma in a 45-year old lady with ovarian metastasis from the undifferentiated component. The primary endometrial tumor showed an undifferentiated component in an otherwise low grade endometrioid carcinoma. The undifferentiated component of these tumors can be misdiagnosed as the solid component of FIGO grade 3 in a pure endometrioid carcinoma. The recognition of an undifferentiated component in an otherwise low grade endometrioid carcinoma is very important, since dedifferentiated endometrioid adenocarcinoma has a worse prognosis when compared with FIGO grade 3 endometrioid carcinoma.

Inhibition of prostate carcinogenesis by combined active immunoprophylaxis.

The aim of this study is to investigate whether an active immunoprophylactic approach combining specific antigens and adjuvant stimuli would be able to inhibit prostate carcinogenesis in transgenic TRAMP mice. A vaccine consisting of allogeneic large T antigen (TAg)-positive SV40-transformed cells combined with systemic recombinant IL-12 was administered to TRAMP mice, starting from when they were still tumor-free at 5-6 weeks of age. The combined vaccine significantly inhibited prostate carcinogenesis, giving a more than doubled median latency time of prostatic tumors (53 weeks in comparison to 26 weeks in control mice). Vaccination with cells alone or IL-12 treatment alone was poorly effective (median latency of 30 and 39 weeks, respectively). The combined vaccine induced a very high CD4 response biased toward the Th1 pathway, with the induction of a humoral response that included TAg-specific antibodies. Therefore, such active immunoprophylactic approach based on the combination of allogeneic SV40 TAg-positive cells and systemic administration of recombinant IL-12 significantly delayed autochthonous urogenital carcinogenesis driven by SV40 TAg in TRAMP mice.