Frequent detection of human herpesvirus-6 sequences by polymerase chain reaction in paraffin-embedded lymph nodes from patients with angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.

In search of a possible involvement of viral agents in angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) and AILD-like lymphoma (AILD-L), we studied the presence of human herpesvirus-6 (HHV-6) in the lymph node biopsies of 12 cases by polymerase chain reaction (PCR). Given the rarity of this lymphoproliferative disorder, we investigated archival specimens, consisting of formalin-fixed and paraffin-embedded tissues, obtained from patients with a clinical and histologic diagnosis of AILD and AILD-L. HHV-6 sequences were detected in the lymph node biopsies of 7 out of the 12 AILD and AILD-L cases examined. HHV-6 sequences were identified also in the involved liver and spleen tissues of one patient and in the PBMCs of two patients, all carrying viral sequences in the affected lymph nodes. We also used PCR to characterize the HHV-6 genomes, showing that two different viral strains are represented in the pathologic tissues. This study provides evidence of the presence of HHV-6 specific sequences in an unexpectedly high proportion of our series of AILD and AILD-L cases, suggesting a possible involvement of this lymphotropic virus in the pathogenesis of at least some cases of the disease.

Primary systemic anaplastic large-cell lymphoma (CD30+): advances in biology and current therapeutic approaches.

In 1985, Stein et al demonstrated the expression of the lymphoid activation antigen CD30/Ki by neoplastic cells. Fifteen years after the first description, anaplastic large-cell lymphomas (ALCL) are now thought to be a heterogeneous group in terms of their clinical, morphologic, phenotypic, cytogenetic, and molecular biology features. However, on the basis of a specific genetic anomaly and expression of a chimeric nucleophosmin anaplastic lymphoma kinase (NPM-ALK) protein and its variants, a distinct clinicopathologic entity defined as "ALK-positive lymphoma" or "ALKoma" can be recognized. Based on molecular and clinical criteria, 3 entities of primary ALCL can be identified: primary systemic ALK positive, primary systemic ALK negative, and primary cutaneous ALCL. This review focuses on advances in the knowledge of primary systemic ALCL biology and discusses therapeutic approaches based on ALK expression. The presence of this protein appears to be an important prognostic factor and, combined with an age-adjusted International Prognostic Index, could allow researchers to design more specific clinical trials aimed at finding new, more efficacious and less toxic treatments.

Cytogenetic and molecular studies in primary myelofibrosis.

Cytogenetic and molecular data of three patients affected by primary myelofibrosis with myeloid metaplasia (PMMM) evolving to blastic crisis are reported. The cytogenetic findings were uncommon. The first patient (female) showed an idic(X)(q13) as the sole alteration in chronic phase, with an additional r(7) in 67% of the cells of the blast crisis; the other two patients showed, in blast crisis, a partial trisomy of the long arm of chromosome 1, without translocation, as a unique structural abnormality. These findings confirm the presence of nonrandom, although nonspecific, alterations in PMMM that, in our cases, seem to be related to the multistep progression of the neoplastic process. Molecular investigations have been applied to study the genomic organization and the level of expression of genes such as bcr and calcyclin and c-fms protooncogene possibly involved in the molecular mechanisms underlying cell proliferation in hematopoietic cells. The data obtained are discussed with respect to the myeloproliferative disorder.

Sinus histiocytosis with massive lymphadenopathy.

To date, the morphological aspects of sinus histiocytosis with massive lymphadenopathy (SHML) have been fully described. The disease is characterized by an enlargement of lymph nodes in which the sinuses are dilated and infiltrated by histiocytes, often phagocytosing lymphocytes. Even if the prognosis is usually benign and not requiring therapy, several fatal cases have been reported. The etiology is still obscure and the biology is not yet completely clear. Recent immunophenotypical studies suggest that histiocytes may belong to the T-zone associated histiocyte lineage. They may be cytologically homogeneous, but can express different antigenic patterns according to their stage of differentiation. Cytogenetic and molecular aspects of the disease have only been sporadically investigated. In order to better understand the pathogenesis of SHML, which seems to be a disorder lying in between the fields of infections, immunological disease and neoplasia, it is considered very useful to systematically employ a variety of immunophenotypical, cytogenetic and molecular techniques to study the disease, particularly in cases which are clinically atypical or with a more aggressive evolution.

HCV and monoclonal gammopathies.

OBJECTIVE: To determine the prevalence of antibodies against HCV in monoclonal gammopathies with and without cryoglobulinemic activity. METHODS: 201 patients were divided into two groups: (I) 94 patients with monoclonal gammopathies with cryoglobulinemic activity, and (II) 107 with monoclonal gammopathies without cryoglobulinemic activity. Cryoglobulins were characterized by immunofixation; HCVAb were detected using second-generation ELISA and RIBA methods; in 38 cases the presence of HCV in peripheral blood mononuclear cells was evaluated by PCR. RESULTS: The HCVAb prevalence, as evaluated by RIBA, in Group I was 69.1% while in Group II it was only 14.9%. Histological and immunohistochemical study of the bone marrow in Group I patients frequently showed signs of nodular B-cell clonal expansion. CONCLUSIONS: Our data confirm the existence of a close correlation between HCV infection and the monoclonal gammopathies with cryoglobulinemic activity. HCV-positive cryoglobulinemic is characterized by self-limiting IgM monoclonal expansion associated with histological aspects of bone marrow lymphoid nodules that do not expand in the course of the disease like classic evolving lymphoproliferative processes.

Leptomeningeal carcinomatosis presenting as progressive multineuritis: clinical, pathologic, and MRI study.

Two patients developed a persistent illness characterized clinically and electrophysiologically by asymmetric involvement of spinal roots, of cranial and peripheral nerves. In the first case the disease was not discovered clinically but only after autopsy. The primary neoplasm remained undetected at autopsy. There was profound infiltration of the leptomeninges by tumor cells with features of metastatic adenocarcinoma. In the second patient onset of neurological symptoms occurred 16 years after surgery for breast cancer, which may be reasonably considered the primary malignancy-CSF cytology was positive only in the second patient in whom Gd-DTPA MRI supported the diagnosis. Our cases demonstrate that diagnosis in leptomeningeal carcinomatosis may be a challenging clinical problem.

Primary high-grade mucosa-associated lymphoid tissue-type lymphoma of the cervix presenting as a common endocervical polyp.

Lymphomas of the uterine cervix are uncommon neoplasms and typically appear as diffuse cervical enlargement. We describe a rare case of primary high-grade lymphoma of mucosa-associated lymphoid tissue of the uterine cervix in a 46-year-old white woman. The tumor, incidentally disclosed at gynecological examination, appeared as a single common polyp. Immunohistochemical investigation found the lesion to consist of a monomorphic CD20-positive infiltrate of large blasts and rare intermingling centrocyte-like lymphoid cells. A dense area of monotypic (lambda light-chain restriction) plasma cells was found beneath the endocervical mucosa; only a few scattered lymphoepithelial lesions were present. The neoplastic cells did not stain for CD5, CD10, CD23, CD43, or cyclin D1. A bone marrow biopsy displayed a paratrabecular, centrocyte-like B-cell infiltration, but no lymphadenopathy was detected by instrumental examination (computed tomographic scan, magnetic resonance imaging). The tumor was successfully treated by multiagent chemotherapy followed by total hysterectomy. To our knowledge, this case represents the second reported example of mucosa-associated lymphoid tissue-type lymphoma occurring in the uterine cervix. We highlight the very unusual gross appearance of this case and emphasize the difficulty of interpreting lymphoid infiltrates in the lower genital tract by microscopy.

Short bowel syndrome: experimental approach to increase intestinal surface in rats by gastric homologous acellular matrix.

BACKGROUND/PURPOSE: In this preliminary work the authors used homologous acellular matrix obtained by the gastric wall to increase the small bowel surface in Sprague-Downey rats; through this experimental model the authors verified that homologous acellular matrix can support cell migration and the reconstruction of the intestinal wall. METHODS: A tract of about 2 cm of tubular gastric acellular matrix was inserted with bilateral anastomosis in an isolated ileal loop, which was located in endoabdominal position through a short subcutaneous tunnel. Twelve animals were analyzed at each of the time-points ranging from 1 to 6 weeks after surgery. RESULTS: Histologic evaluation showed that the implanted matrix can be reintegrated in the normal small bowel in a period ranging between 3 and 6 weeks from surgery. The implanted matrix was organized with 4 different tonacae from the third week after the surgery, without interruption at the site of the anastomosis. CONCLUSIONS: To date, the authors do not have a demonstration of the function of the ileal loop reconstructed with this technique; based on these results the authors are engaged in an experimental trial of restoration of intestinal viability with the ileal prosthesis after 3 weeks to study its function.

A report of seven long survivors for evidence of prognostic factors in hairy cell leukemia.

The clinical hematologic and pathologic findings of 30 patients with hairy cell leukemia observed between 1966 and 1979 were studied. Twelve patients had long-lasting course of the disease. Seven of them displayed a survival greater than or equal to 120 months, whereas 18 patients died within 36 months of the diagnosis. Their clinical and laboratory characteristics (age of onset, sex, ESR, hemoglobin, WBC, neutrophils, monocytes, platelets, spleen and liver size) were analyzed to ascertain possible prognostic features. Multivariate discriminant analysis, performed both with a direct method and with a stepwise method (Wilks' method), provided a discriminant function able to correctly predict the prognosis of the disease in 83.3% of the examined cases. Spleen size, neutrophil count, age of onset, ESR and liver size turned out to be the most important prognostic factors; in contrast, splenectomy did not significantly affect the prognosis in our cases.

[Malignant histiocytosis. Histiocytic medullary reticulosis]. / Istiocitosi maligna. Histiocytic medullary reticulosis.

The Authors report a case of malignant histiocytosis apparently localized only in the spleen. The diagnosis of the disease, characterized at the onset by moderate leukopenia and thrombocytopenia, was made possible by the histopathologic examination of the spleen following splenectomy. The disease shows a chronic course. The Authors discuss the clinical and histological features of the case.

[Unusual association of hemolytic anemia and splenic metastases in a case of breast carcinoma]. / Rara associazione di anemia emolitica e metastasi spleniche in un caso di carcinoma mammario.

An unusual case of splenic metastasis associated with haemolytic anaemia in a patient with breast cancer is reported. Attention is drawn to the rarity of invasion of the spleen, and an account is given of the causes of haemolytic anaemia in carcinomatosis. A spectacular response to splenectomy was observed in the case reported.

[Aplastic anemia and myelodysplasia: a not-always-easy distinction]. / Anemia aplastica e mielodisplasia: una distinzione non sempre agevole.

The differential diagnosis between Myelodysplasia and Aplastic anaemia may be sometimes difficult, because clinical and morphological features may appear similar. Two cases, a Myelodysplastic syndrome with hypocellular and an Aplastic anaemia with hypercellular BM aspirates, are described in this report. Reciprocal connections between these two pathological entities, some biological aspects and the value of BM biopsy are also discussed.

[Tuberculous lymphadenitis. Apropos of a non-typical histological picture]. / Linfoadenite tubercolare. A proposito di un quadro istologico non tipico.

The case is presented of a young Somali with acute lymphadenitis. Whereas histological examination indicated abscessing granulomatous lymphadenitis, bacteriological studies revealed the presence of M. tuberculosis in the pus taken from the lymph node. Hence the aetiological diagnosis contradicted the morphological picture.

[Idiopathic myelofibrosis associated with an IgM-secreting immunocytoma]. / Mielofibrosi idiopatica associata ad immunocitoma IgM secernente.

A case of idiopathic myelofibrosis developing in conjunction with IgM secreting immunocytoma is described. The possible pathogenetic implications of the association between myeloproliferative and lymphoproliferative disorders are discussed.