Latent Epstein-Barr virus infection is an unlikely event in the pathogenesis of immunoproliferative small intestinal disease.

BACKGROUND: The observed seasonal and geographic variations in the incidence of immunoproliferative small intestinal disease (IPSID) suggest that environmental factors contribute to its pathogenesis. One such environmental factor, the Epstein-Barr virus (EBV), has been associated with other B-cell lymphoproliferative disorders. METHODS: IPSID tissues obtained at the time of initial diagnosis were retrieved from the American University of Beirut pathology archives (1972-1983) and examined for EBV genetic information by colorimetric in situ hybridization (ISH) and polymerase chain reaction (PCR). Eight patients were identified, four of whom also had serologic and immunohistochemical evidence of alpha-heavy chain disease. Thirteen tissue samples from these eight patients were available for study: eight were intestinal and five were nodal. Non-Hodgkin's B-cell lymphoma cases (nine) were randomly selected from the same archive to serve as a control for EBV in that geographic location. The ISH method used a probe to the "W" repetitive region of EBV, with the human placental DNA probe as a control for sample preparation. The PCR method amplified a 110 base pair region in the long internal direct repeat with amplification of beta-actin as control for DNA preservation. Both assays used formalin fixed paraffin embedded Raji cells as a positive control. RESULTS: Neither ISH nor PCR demonstrated EBV in any of the eight patients with IPSID: The results for one of seven control blocks with adequate DNA preservation were positive when PCR was used but were negative when ISH was used. CONCLUSIONS: These findings do not support a role for EBV in the induction of B-cell proliferation in IPSID:

Mature B-cell acute leukemia: a clinical, morphological, immunological, and cytogenetic study of nine cases.

Nine patients who presented with acute lymphoid leukemia of mature B-cell phenotype without FAB-L3 morphology are discussed. All patients were male with a median age of 69 years. All patients had extensive bone marrow involvement at presentation with lymphoid leukemic cells in the peripheral blood. Six patients had extramedullary disease and 3 developed meningeal involvement sometime during the course of their illness. The leukemic cells were negative for terminal deoxynucleotidyl transferase in all 9 cases, and monoclonal surface immunoglobulin was demonstrated in all 8 cases evaluated with a lambda light chain predominance. Clonal chromosomal abnormalities were detected in 4 of 6 cases studied with no specific pattern identified, although abnormalities involving chromosome 8 were present in all 4 cases. Despite aggressive chemotherapy, only 2 patients achieved complete remission which was of short duration (1 month) in 1 patient. Eight patients died of their disease 1 week to 20 months after diagnosis with a median survival of 5.5 months. Mature B-cell acute leukemias that are not of the FAB-L3 type have a very aggressive clinical course and poor prognosis.

Acquired renal cystic disease in end-stage renal disease: an autopsy study of 155 cases.

Autopsy reports on 155 successive end-stage renal disease (ESRD) patients and 147 control patients without ESRD, matched for age, race and gender, were collected. Cystic transformation of the kidneys was noted in 58% of the ESRD patients and 13.6% of the control patients. There were 25 ESRD patients with renal adenoma and 3 with renal cell carcinoma. The single best predictor of cystic transformation or tumorous degeneration was patient's age. A statistically significant association between cystic transformation and gender, as well as the cause of ESRD, was also found. In contrast to previous reports we were unable to document a strong association between the incidence of either cystic transformation or tumorous degeneration with the duration of dialysis, nor did these two parameters correlate with mode of dialysis. We suggest that cystic transformation of the kidneys in ESRD is related to age and renal failure per se, is not strongly associated with duration of dialysis and is independent of mode of dialysis. Concomitant tumorous degeneration was frequent, but this was usually an incidental autopsy finding. Renal malignancy was uncommon and metastases were absent.

Light chain cast nephropathy and acute renal failure associated with rifampin therapy. Renal disease akin to myeloma kidney.

Acute renal failure developed in a patient with a normal serum creatinine level, after treatment with rifampin was begun for tuberculosis. Renal biopsy revealed an obstructive nephropathy due to tubular casts. Immunoperoxidase and immunofluorescence studies demonstrated the presence of heterogeneous light chains within these casts. This unique drug-induced renal disease is discussed with reference to the literature and to possible analogies with myeloma kidney.

Common variable hypogammaglobulinemia complicated by an unusual T-suppressor/cytotoxic cell lymphoma.

A patient with common variable hypogammaglobulinemia (CVH) who presented with recurrent sinopulmonary infections, nodular lymphoid hyperplasia of the small bowel, and intestinal giardiasis was studied. A diffuse lymphocytic lymphoma with small bowel, skin, and hepatic involvement subsequently developed in the patient. Light microscopy of the tumor revealed tissue infiltration with mononuclear cells having the morphologic features of T-lymphocytes. The malignant lymphocytes had characteristics of T-suppressor/cytotoxic cells as established by the absence of surface immunoglobulin and Leu 3 surface markers, and the presence of OKT3 and OKT8 surface markers. Peripheral blood lymphocyte studies revealed an increased number of T-suppressor cells, a reversal of the helper-suppressor ratio, and a generalized state of hyporesponsiveness to mitogen and antigen stimulation. No evidence of retroviral reverse transcriptase activity was detected in cultures of peripheral blood lymphocytes. The association between CVH and a lymphoma composed of cells with T-suppressor/cytotoxic surface markers has not been previously reported. The postulated role of T-suppressor cells in the failure of immunoglobulin synthesis in some forms of CVH suggests that the finding of a T-suppressor/cytotoxic cell lymphoma complicating CVH may be more than fortuitous.

Biclonal gammopathy (IgG kappa and IgG lambda) in a patient with non-Hodgkin's lymphoma.

We report a case of non-Hodgkin's malignant lymphoma with biclonal gammopathy (IgG kappa and IgG lambda) involving both serum and urine. Detailed immunologic studies of the tumor disclosed two morphologically indistinguishable clones of cells that were responsible for the production of the two monoclonal immunoglobulins. This, to our knowledge, is the first documented case of a biclonal gammopathy involving a single heavy-chain class with both kappa and lambda light chains in a non-Hodgkin's lymphoma. Lesions resembling lymphomas must not be assumed to be inflammatory simply because the cells express both kappa and lambda antigens.

Endometrial carcinoma of the prostatic utricle: a tumor of prostatic origin.

Endometrial carcinoma of the prostatic utricle previously was believed to be of müllerian origin. We report 2 cases studied by ultrastructural and immunoperoxidase techniques. Our results, as well as those presented by others, demonstrate the prostatic origin of this tumor.

Cardiac papilloma. A case report with evidence of thrombotic origin.

A pulmonic valve cardiac papilloma was found in a patient with coagulopathy and disturbed right ventricular hemodynamics. Fibrin was demonstrated within the cores of the papillae, lending further support to the thrombotic derivation of these lesions. The tumor's papillary configuration was thought to be the result of molding by the turbulent blood flow at that site.

Burkitt cell leukemia following therapy for Hodgkin disease.

Two adults with advanced Hodgkin disease-one treated with combination chemotherapy, and one with chemotherapy and radiation therapy-developed Burkitt cell leukemia four and seven years after diagnosis, proved by cytochemical and ultrastructural study. Acute lymphocytic leukemia must be considered in the evaluation of therapy-related leukemias.

Familial osteogenic sarcoma occurring in pagetoid bone.

In a father and son who had familial Paget's disease of bone, secondary osteogenic sarcomas involving identical anatomic sites developed at about the same age. A review of the literature revealed 35 additional cases of familial osteogenic sarcoma arising in 14 families, mainly among siblings. The relationship of osteogenic sarcoma to Paget's disease and the familial aspects of both conditions are discussed. This is the first recorded instance of a vertical male-to-male transmission of Paget's disease and osteosarcoma.

Importance of terminal hepatic venule thickening.

Thickening around the terminal hepatic venule (THV) in alcoholics has been implicated as a marker for fibrosis and cirrhosis. To test this hypothesis, we evaluated 107 liver biopsy specimens from patients with normal liver histologic features (12), fatty livers (30), mild alcoholic hepatitis (15), and florid alcoholic hepatitis (29). Twenty-one follow-up liver biopsy specimens from patients with fatty liver and alcoholic hapatitis were also available for this study. Two observers (S.M.N., V.H.N.) graded 18 histologic features on a scale of 0 to 3. There was no significant difference in the prevalence of THV thickening in normal biopsy specimens and in various forms for alcoholic liver injury. There was also no correlation between the degree of THV thickening and steatosis, necrosis, or inflammation. Thickening of the THV was most common in the presence of lobular and subsinusoidal fibrosis. Cirrhosis developed in nine of ten alcoholic patients who had subsinusoidal and lobular fibrosis. These findings illustrate that the marker for progressive fibrosis and development of cirrhosis is lobular and subsinusoidal fibrosis and not the isolated thickening of the THV.

Cystic lymphangioma of the spleen.

Splenic cysts are uncommon, with fewer than 600 cases reported in the world literature. This report concerns a case of cystic lymphangioma of the spleen, consisting of a large splenic cyst with associated multiple, small, subcapsular cysts and lymphangiectasia. The cysts are lined by endothelium, and they conform to the characteristics of dilated lymphatic channels. Lymphangioma of the spleen is thought to arise from congenital obstruction of lymphatic flow, with subsequent dilatation of lymphatic channels. The diagnosis and treatment of splenic cysts are discussed and a new classification of splenic cysts is proposed.

Genetic and immunological aspects of familial chronic active hepatitis (type B).

Thirteen family members of a patient with chronic active hepatitis type B were investigated. The family included both parents, 6 sons, and 5 daughters. The parents were second cousins. HBsAg, liver tests, immunological evaluation, and HLA typing were performed on all subjects. Percutaneous liver biopsies were done on the mother and 5 of the 6 sons. The mother and all 6 sons had HBs antigenemia. The mother was free from any evidence of liver disease whereas all 6 sons had abnormal liver and immunological tests. The liver biopsies of 5 sons showed chronic active hepatitis with variable degrees of progression toward cirrhosis. The 6th son could not be biopsied in view of his prolonged prothrombin time. The father and the 5 daughters were HBsAg negative and had no evidence of liver disease. Immunological abnormalities were present in all of the effected children and in the mother and 3 daughters. This is the second report in the English literature on the familial occurrence of chronic active hepatitis type B. It emphasizes the predominance of this entity in the male offspring and confirms the presence of immunological abnormalities in the relatives of such patients. There was no evidence to link the inheritance of an immunological abnormality to clear the HBsAg to the histocompatibility complex.

The association of adenocarcinoma of the lung and blastomycosis from an unusual geographical location.

A case of North American blastomycosis acquired outside the American continent and presenting with a left hilar mass is reported. The progressive hilar enlargement, despite adequate antifungal treatment, raised the possibility of drug resistance, concomitant tuberculosis and carcinoma. Non-invasive diagnostic studies including cultures, cytology and fibreoptic bronchoscopy were negative. On thoracotomy, both blastomy cosis and a poorly undifferentiated adenocarcinoma were evident.

"Mediterranean abdominal lymphoma" or immunoproliferative small intestinal disease. Part II: pathological aspects.

The pathology of 25 cases of Mediterranean abdominal lymphoma, better designated as immunoproliferative small intestinal disease (IPSID), are reported from the American University of Beirut Hospital. The series includes nine cases with documented alpha heavy chain disease (alpha-HCD). The disease is characterized by the presence of a diffuse and compact bandlike lymphoplasmacytic infiltration of the proximal small intestinal mucosa. The presence of a concomitant malignant lymphoma in the intestine and/or mesenteric lymph nodes, and of alpha-heavy protein in the serum is commonly encountered. Two histopathologic variants of IPSID are present. The first is characterized by the diffuse infiltration of the mucosa, at sites away from tumoral masses, by either pure plasmacytic infiltration, or mixed lymphoplasmacytic infiltration. This variety is associated with the immunoblastic sarcoma type of malignant lymphoma, and with alpha chain disease (alpha-HCD). The second variant is characterized by a diffuse follicular lymphoid hyperplasia pattern in the small intestinal mucosa. The associated malignant lymphoma is diffuse and undifferentiated often having a starry-sky pattern. This variety is not associated with alpha-HCD. Both histologic variants share the same clinical antecedents. In five patients, mesenteric lymph nodes harbored immunoblastic sarcoma while the intestinal mucosae of the same patients were involved with a benign appearing lymphoplasmacytic infiltration. This finding stresses the need for staging laparatomy. Three patients, with alpha-HCD, had peripheral lymph node involvement with immunoblastic sarcoma. The disease apparently evolves in two stages: an immunoproliferative phase, probably reversible, and a later development of malignant lymphoma. The term immunoproliferative small intestinal disease accurately describes the nature of the entity.

Enteric fever: a clinicopathologic study of 104 cases.

The records of 104 patients with culture-proven enteric fever were reviewed and evaluated as to the clinical signs, laboratory findings, pathologic features and complications of the disease. One patient with fatal disseminated intravascular coagulation and enteric fever is also presented. Fever and bradycardia were the leading clinical signs followed by splenomegaly, hepatomegaly and rose spots. The principal complications of enteric fever included anemia, typhoid hepatitis, relapse and bleeding. Evidence of typhoid hepatitis was present in 30% of the patients tested. The pathology consisted of typhoid nodules of variable frequency and size depending upon the severity of the condition. The relationship of typhoid hepatitis to relapse seems to be more than coincidental as four out of seven patients who had relapse had abnormal liver tests. The occurrence of disseminated intravascular coagulation in enteric fever is rare; however, awareness of such a potential complication may be life-saving to the patient.

Direct immunofluorescence in the diagnosis of toxoplasmic lymphadenitis.

The diagnosis of toxoplasmic lymphadenitis was established through the demonstration, by direct immunofluorescence, of toxoplasma cysts and trophozoites in a cervical lymph node biopsy which also had a characteristic histopathology. The patient had cervical lymphadenopathy and increased specific fluorescent antitoxoplasma IgG and IgM antibodies.