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.

Persistent polyclonal B lymphocytosis: morphological, immunological, cytogenetic and molecular analysis of an Italian case.

We describe a case of persistent polyclonal B-cell lymphocytosis (PPBL) studied by morphological, immunological, cytogenetic and molecular analysis. PPBL is a rare lymphoproliferative disorder with an unclear natural history. Although a few cases of malignancies are observed during PPBL, this disorder is usually considered to be an indolent syndrome. A longer follow-up in a larger number of patients is needed in order to clarify the natural history of PPBL and its potential to transform into a malignancy. As PPBL is a rare disease, establishing an international PPBL registry could be the most effective way to understand the natural history of this disease and to discover its etiologic factors.

Human herpesvirus 6 latently infects early bone marrow progenitors in vivo.

We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways.

Expression of human herpesvirus-6 antigens in benign and malignant lymphoproliferative diseases.

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas, 14 Hodgkin's disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called "mummified" Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder.

Lymphotropic herpes virus (EBV, HHV-6, HHV-8) DNA sequences in HIV negative Castleman's disease.

Aim-To evaluate the possible involvement of lymphotropic herpes viruses in Castleman's disease.Methods-Archival formalin fixed, paraffin wax embedded biopsy specimens from 16 HIV negative patients (11 with localised and five of multicentric disease) were studied. Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and human herpes virus-8 (HHV-8) DNA was detected using PCR. PCR was also used to characterise the EBV genomes and the clonal status of the lesions.Results-EBV sequences were identified in nine (56%) cases. The main EBV genotype detected was type 1. Two (12%) cases were positive for both HHV-6 and EBV sequences. HHV-8 sequences were detected in one case of localised Castleman's disease, the sequence of which differed from that of the HHV-8 prototype. No clonal immunoglobulin gene rearrangements were found.Conclusions-EBV DNA was detected in a substantial proportion of cases, suggesting that it may have a role in the pathogenesis of Castleman's disease, unlike HHV-6 which was detected rarely. This is the first report of HHV-8 specific sequences in the localised from of the disease.

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.

[Noma in a patient with acute leukemia allergic to penicillin]. / Noma in paziente con leucemia acuta allergica alla penicillina.

Noma has virtually disappeared from Europe, but is still found in certain parts of Africa, South America and Asia. In our case the etiologic agent was Pseudomonas aeruginosa sensitive to antibiotic therapy that we used (pefloxacin and netilmicin). Another characteristic aspect of our case is the rapid infaust evolution. In this report will be discuss the pathogenesis and the reason of the failure of the antibiotic therapy especially in immunodeficiency patients.

[Efficacy of erythropoietin in anemia of patients with immuno-lymphoproliferative disease]. / Efficacia dell'eritropoietina nell'anemia dei pazienti con malattie immuno-linfoproliferative.

Anemia is a common complication of lymphoproliferative syndromes. The exact pathogenic mechanism of this anemia is unclear. Many patients require progressive and persistent blood transfusions. We treated 10 patients (8 with multiple myeloma, 1 with non Hodgkin Lymphoma, 1 with chronic lymphocytic leukemia) by administering low doses of recombinant human erythropoietin (60 U/kg 3 times a week s.c.). All patients presented anemia with hemoglobin levels less than 10 gr/dl; renal function was not impaired (serum creatinine levels less than 1.2 mg/dl or creatinine clearance greater than 60 ml/min). A response was defined as an increase of hemoglobin level of at least 2 gr/dl or stop of red-cell transfusion within the first 3 months of treatment. Nine patients (90%) responded to treatment with a significant increase in the hemoglobin concentration. Two patients presented a cerebral stroke not correlated with erythropoietin administration.

A cytomorphological and immunohistochemical study of bone marrow in the diagnosis of essential mixed type II cryoglobulinemia.

BACKGROUND: Type II essential cryoglobulinemia may be associated with a lymphoproliferative disorder of beta lineage that shows a low degree of malignancy. METHODS AND RESULTS: The authors report a case recorded of 35 patients (30 females and 5 males) affected by mixed cryoglobulinemia type II (MC II) that has been typed by immunofixation, a procedure that allows the identification of minute amounts of monoclonal components. In 20 patients with the "essential" form, the bone marrow histology revealed the presence of nodular aggregates of lymphocytes that were consistent with the diagnosis of immunocytoma in 14 cases and of early stage plasmocytoma in 1 case. The immunohistochemical analysis carried out in 5 of these cases allowed the identification of B lymphocytes in the nodules, thus confirming the diagnosis of low malignancy lymphoma. In our series the percentage of proliferative disorders of B lymphocyte lineage was 66%. CONCLUSIONS: Our results indicate that the cytohistological analysis of bone marrow is highly recommended in the study of essential mixed cryoglobulinemia and that histological analysis supplemented with immunohistochemistry is preferred to the simple cytological analysis of bone aspirate.

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.

New clinical criteria for the assessment of liver involvement in Hodgkin's disease.

The hepatic involvement in Hodgkin's disease, histologically verified in 133 patients who underwent laparotomy or laparoscopy, proved to be singly related to the following clinical findings: result of the liver isotopic scan, liver and/or spleen enlargement, serum albumin less than or equal to 3.5 g/dl, GOT and/or GPT greater than or equal to 20 mU/ml, serum alkaline phosphatase (SAP) greater than or equal to 210 mU/ml, BSP retention at 45 min greater than or equal to 6.5% and ESR greater than or equal to 51 mm at 1 hr. Such clinical findings were jointly evaluated and further selected by means of a logistic discriminant analysis, and the simplest function with the best discriminant ability between involved and non-involved liver was made by liver scan, spleen enlargement, BSP retention and GOT (89.5% of correct diagnoses). Since the Ann Arbor clinical criteria for liver involvement showed correct diagnoses in 69-80% of the cases, more reliable criteria can be proposed. So, liver involvement is highly probably (a) when three or more of the five variables indicated above are abnormal, or (b) when a markedly abnormal liver scan is associated with alteration of at least one of the other four parameters: otherwise liver will be non-involved.