Deficiency of the LIM-only protein FHL2 reduces intestinal tumorigenesis in Apc mutant mice.

BACKGROUND: The four and a half LIM-only protein 2 (FHL2) is capable of shuttling between focal adhesion and nucleus where it signals through direct interaction with a number of proteins including beta-catenin. Although FHL2 activation has been found in various human cancers, evidence of its functional contribution to carcinogenesis has been lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we have investigated the role of FHL2 in intestinal tumorigenesis in which activation of the Wnt pathway by mutations in the adenomatous polyposis coli gene (Apc) or in beta-catenin constitutes the primary transforming event. In this murine model, introduction of a biallelic deletion of FHL2 into mutant Apc(Delta14/+) mice substantially reduces the number of intestinal adenomas but not tumor growth, suggesting a role of FHL2 in the initial steps of tumorigenesis. In the lesions, Wnt signalling is not affected by FHL2 deficiency, remaining constitutively active. Nevertheless, loss of FHL2 activity is associated with increased epithelial cell migration in intestinal epithelium, which might allow to eliminate more efficiently deleterious cells and reduce the risk of tumorigenesis. This finding may provide a mechanistic basis for tumor suppression by FHL2 deficiency. In human colorectal carcinoma but not in low-grade dysplasia, we detected up-regulation and enhanced nuclear localization of FHL2, indicating the activation of FHL2 during the development of malignancy. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that FHL2 represents a critical factor in intestinal tumorigenesis.

[Langerhans cell histiocytosis in an adult patient associated with sclerosing cholangitis and cerebellar atrophy]. / Histiocytose langerhansienne de l'adulte avec cholangite sclérosante et atrophie cérébelleuse.

Langerhans' cell histiocytosis is a disorder in children or young adults, characterized by clonal proliferation of histiocytic cells, staining for CD1a, with uni or multifocal organ involvement. It's a rare condition in adults. We report a case of Langerhans' cell histiocytosis in an adult with sclerosing cholangitis which rapidly progressed to fatal liver failure and progressive cerebellar atrophy. Langerhans cell histiocytosis is a rare cause of sclerosing cholangititis in adults.

Primitive neuroectodermal tumor of the stomach.

Ewing sarcoma/primitive neuroectodermal tumor is classically a tumor of the soft tissue or bone in children and young adults, but several cases have been described in patients of all ages. Within the last decade, the clinicopathologic spectrum of Ewing sarcoma/primitive neuroectodermal tumor has been markedly expanded by recognition that the tumor may also have a visceral origin. We describe a case of primitive neuroectodermal tumor arising in the stomach of a 66-year-old woman. The neoplasm was excised using a radical surgical procedure. Microscopically, the tumor was made up of solid nests and sheets of round cells. Immunohistochemically, the tumor cells showed immunoreactivity for CD99, S100, neuron-specific enolase, and vimentin. A multiplex real-time polymerase chain reaction assay detected an EWS-ERG fusion. To our knowledge, this is the first description of a primitive neuroectodermal tumor arising in the stomach.

[Unusual parosteal osteochondromatous proliferation or Nora's tumor. A clinicopathological analysis of 4 cases]. / Prolifération ostéocartilagineuse parostéale bizarre ou tumeur de Nora. A propos de quatre observations.

Nora's lesion, also known as bizarre parosteal osteochondromatous proliferation (B.P.O.P.), involves mostly the small tubular bones of the hands and feet. Histologically, it is characterized by a proliferation of chondroid, bony and fibrous tissues, sometimes with high cellular density, bizarre chondrocytes but is devoid of cellular atypia and necrosis. Distinct blue color is noted at the interface of bone and cartilage. The most important lesions that present differential diagnostic problems are chondrosarcoma, parosteal osteosarcoma and florid reactive periostitis. The lesion is benign but may recur locally in as many as 55%. The clinical and pathological findings of four cases of Nora's lesion are presented.

[Postmenopausal frontal fibrosing alopecia. Report of 3 cases]. / Alopécie frontale fibrosante post-ménopausique.

Postmenopausal frontal fibrosing alopecia is a rare aspect of scarring alopecia concerning elderly women. It appears as a receding anterior hair line localised in the frontal and temporal regions. It is a particular pathologic and clinical form of lichen planopilaris. The histologic aspect is that of a lichenoïd inflammatory infiltrate affecting the dermal follicular junction, accompanied by a fibrous scarring aspect, the latter contributing to the diagnosis and individualization of this entity. Discoïd lupus erythematous is the main histologic differential diagnosis. Postmenopausal period is the only associated condition found in affected women. Evolution is unpredictable and does not seem to be modified by treatment.

[Renal tuberculosis and renal adenocarcinoma: a misleading association]. / Tuberculose rénale et adénocarcinome du rein: une association trompeuse.

The association of renal cancer and renal tuberculosis is uncommon. While the incidental discovery of renal cell carcinoma in a tuberculous kidney is a classical finding, the discovery of tuberculous lesions after nephrectomy for cancer is exceptional. The authors describe the case of a patient operated for renal cancer in whom histological examination revealed associated renal tuberculosis.