Myron Susin

Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposis sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposis sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposis sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.

Cholinergic agonists attenuate renal ischemia–reperfusion injury in rats

Inflammation plays a significant role in the pathophysiology of renal ischemia-reperfusion injury. Local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors such that electrical or pharmacologic stimulation of this cholinergic anti-inflammatory pathway results in suppression of proinflammatory cytokine production. We examined the effects of cholinergic stimulation using agonists, nicotine or GTS-21, given before or after bilateral renal ischemia-reperfusion injury in rats. Pretreatment of rats with either agonist significantly attenuated renal dysfunction and tubular necrosis induced by renal ischemia. Similarly, tumor necrosis factor-alpha protein expression and leukocyte infiltration of the kidney were markedly reduced following treatment with cholinergic agonists. We found functional nicotinic acetylcholine receptors were present on rat proximal tubule epithelial cells. Cholinergic stimulation significantly decreased tubular necrosis in vagotomized rats after injury, implying an intact vagus nerve is not required for this renoprotective effect.

Lipoid nephrosis in Hodgkin's disease

Abstract Two cases of Hodgkins disease presenting as the nephrotic syndrome are described. Evaluation of the renal biopsy specimens by light microscopy, electron microscopy and immuno-fluorescent antibody staining was most compatible with a lipoid nephrosis type of lesion. In both cases there was a prompt and prolonged remission of the nephrotic syndrome when the Hodgkins disease was treated with radiation therapy.

Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection

Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1.

Histiocyte-rich B-cell lymphoma

This is the second report of histiocyte-rich B-cell lymphoma and the first case analyzed by flow cytometry and cytogenetic study. The immunophenotype determined by flow cytometry was that of a B-cell antigen-positive, surface immunoglobulin-negative B-cell lymphoma with 79% CD11c positive histiocytes. The lymphoid cells were composed of 76% neoplastic B-cells and 24% reactive T-cells. Immunohistochemical staining showed large numbers of histiocytes positive for CD68 and lysozyme in the lymph node and the bone marrow. Neoplastic lymphoid cells were positive for CD20, CD45, CD74 and CDw75. The monoclonality of the tumor cells was established by the evidence of rearrangements of the heavy chain and kappa light chain genes and a complex clonal cytogenetic abnormalities including t(8;14)(q11;q32). The tumor cells were large, pleomorphic lymphoid cells and showed no features resembling those of the L/H cells of Hodgkins disease as previously reported. The rapidly progressive clinical course in the present case is consistent with the clinical features shown in the original study. The histiocytic component in this tumor is presumably recruited by a lymphokine with the nature of a growth factor from the tumor cells that may also be responsible for the rapid proliferation of the tumor cells and the aggressive clinical course. This entity merits special recognition because it leads to a predictable poor prognosis and because of its potential of being misdiagnosed as true histiocytic lymphoma.

Mutational Status of Codons 12 and 13 of the N- and K-ras Genes in Tissue and Cell Lines Derived from Primary and Metastatic Prostate Carcinomas

N- and K-ras mutations at codons 12 and 13 were investigated using oligonucleotide hybridization analysis after PCR amplification and subsequent sequence analysis of the amplified DNA from the region of interest in the following prostatic primary and metastatic (met) carcinoma-derived cell lines: 1013L (primary), PC3 (bone met), DU145 (brain met), and LNCaP (lymph node met). We also examined fresh and archival primary and metastatic prostate tumor tissue and benign prostatic hypertrophy specimens. All prostatic cells and tissues examined contain at least one wild-type N- and K-ras allele with respect to codons 12 and 13. No mutations were found at N-ras codon 13. The only mutation seen in the prostatic cell lines and tissues was a K-ras codon 12 position II G-to-T transversion. Since these are established nonclonal cell lines that have adapted to tissue culture, it is possible that this mutation does not represent the mutational state of prostatic carcinoma in vivo. However, the lack of consistent mutation in the ras genes amplified directly from tumors suggests that when ras mutations occur during the progression of prostatic carcinoma, they are late-stage events not directly involved in the initial development of disease. Immunoprecipitation studies using pan-ras antibodies revealed no evidence of altered expression of Ras proteins.

The clonal origin of two cell populations in Richter's syndrome

A case of Richters syndrome was studied by morphology, immunohistochemistry, flow cytometry, and immunoglobulin gene rearrangement. Flow cytometric study clearly demonstrated two monoclonal populations. The use of double staining with CD 5/CD 19 antibodies accompanied by two-color flow cytometric analysis clearly defined the chronic lymphocytic leukemia population and separated it from the lymphoma population. Immunoglobulin heavy-chain gene analysis of blood and lymph node specimens revealed nonidentical as well as identical nongermline bands in these two populations. However, light-chain gene analysis demonstrated that both populations shared a common clonal origin. This result underscores the unreliability of using heavy chain genotype alone to identify clonal origin. Since post-rearrangement deletion, point mutation, and heavy chain switching occur in heavy chain genes, but are seldom seen in light chain genes, it is important to analyze both heavy and light chain genes to conclusively determine clonal origin.

Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil

Abstract We report a 21-year-old male with childhood-onset familial nephrotic syndrome and frequent relapses who manifested toxicity or treatment resistance to corticosteroids, cyclophosphamide, cyclosporin-A, and tacrolimus. Monotherapy with mycophenolate mofetil (MMF) resulted in maintenance of clinical remission for 14 months without noticeable toxicity, while allowing resolution of steroid-induced side effects. Our observation suggests that MMF may be useful in maintaining remission in nephrotic patients who manifest toxicity to standard immunosuppressive agents.

Kidney transplant nephrotic syndrome.

Abstract The incidence and clinical spectrum of nephrotic syndrome following kidney transplantation was evaluated in 81 patients who received a transplant between 1963 and 1971, and whose transplant functioned more than 10 months. The nephrotic syndrome developed in 24 patients (29.6 per cent). Eighteen patients received kidneys from living related donors, and six from cadaver donors. The original kidney disease was chronic glomerulonephritis in 15 patients and nonimmunologic diseases in 9. The over-all incidence of the transplant nephrotic syndrome did not differ between these two groups of patients. However, in patients with chronic glomerulonephritis, who had the nephrotic syndrome in the course of their original disease, the incidence of transplant nephrotic syndrome was higher than in those without a history of nephrotic syndrome. Most patients had one or more episodes of rejection prior to the onset of the nephrotic syndrome, and in about two thirds of the patients the nephrotic syndrome developed within 1 year after transplantation. Pathologic studies suggest that chronic rejection is the most common cause of the transplant nephrotic syndrome. The majority of patients had hypoalbuminemia and hyperlipidemia with increased beta lipoprotein, but urine protein was fairly selective, and the patients had minimal edema. Creatinine clearance at the beginning of the nephrotic syndrome was 10 to 70 ml/min (average 47 ml/min). Thirteen patients continued to do well for 16 to 94 months (average 51 months) after receiving their transplant with an average creatinine clearance of 47 ml/ min. There was no significant difference in graft or patient survival between transplant recipients who had the nephrotic syndrome and those who did not. Once the nephrotic syndrome is established, it appears to persist regardless of steroid or other immunosuppressive therapy.

Meningeal involvement in IgD myeloma with cerebrospinal fluid paraprotein analysis

Myelomatous meningitis is a rare occurrence in multiple myeloma. We report 2 cases of documented IgD myeloma with cytologic evidence of meningeal involvement in 1 and detailed paraprotein analysis in both. The occurrence of meningeal involvement in this rare form of plasma cell neoplasm may be more common than previously thought. Cancer 46:152–155, 1980.