Jun Hanai

Lymphoproliferative disorders in renal transplant patients in Japan

Post‐transplantation lymphoproliferative disorders (PT‐LPD) are characterized by a clinically and morphologically heterogeneous group of lymphoid proliferation occurring after organ or bone marrow transplantation. The immunodeficient state provides a basis for lymphomagenesis probably through activation of oncogenic viruses. Twenty‐four patients in whom PT‐LPD developed after renal transplantation in Japan were analyzed. They received hemodialysis for 4 to 226 (median 13) months before transplantation. In situ hybridization was performed to detect Epstein‐Barr virus (EBV). Polymerase chain reaction and Southern hybridization with primers in the tax and pol regions of human T‐cell leukemia virus type I (HTLV‐1) were performed on DNA extracted from paraffin‐embedded specimens. Immunohistochemical analysis revealed that 12 cases were B‐cell type, 10 cases (42%) T‐cell type and 2 NK‐cell type. Five of the T‐cell cases were classified as adult T‐cell lymphoma with proven HTLV‐1 genome in the tumor and seropositivity for the virus. These cases were classified as adult T‐cell lymphoma (ALT). More than 80% of B‐cell, 30% of T‐cell and both NK/T‐cell lymphomas were EBV‐positive. Co‐infection of EBV and HTLV‐1 was found in 2 cases with ATL. These findings showed that ATL is common among Japanese renal transplant patients, which might be due to transmission of HTLV‐1 via blood transfusion during hemodialysis.

RENAL NEOPLASIAS IN PATIENTS RECEIVING DIALYSIS AND RENAL TRANSPLANTATION: CLINICO-PATHOLOGICAL FEATURES AND P53 GENE MUTATIONS

BACKGROUND In Japan, the relative risk for renal cell carcinoma (RCC) in renal transplants was about 80-fold higher than that in the general population. Depressed immune surveillance due to the use of immunosuppressive agents was considered to cause cancer. Before renal transplantation, a vast majority of patients received hemodialysis, a known causative factor for acquired cystic disease of kidney (ACDK). Because ACDK is also considered to predispose to RCC, at least two risk factors for cancer accumulate in renal transplants. METHODS In our study, clinicopathological features together with p53 gene mutations were analyzed in 218 patients with RCC: 22 received dialysis followed by renal transplantation, 39 received dialysis alone, and 157 sporadic RCC. P53 mutations were analyzed on DNA extracted from paraffin-embedded specimens with use of single strand conformation polymorphism, followed by direct sequencing. RESULTS RCC in transplants shared several clinicopathological features with those in dialysis patients, which included small size and multiplicity of tumor, relatively high frequency of presence of ACDK, and papillary type of RCC. p53 gene mutations were infrequent in RCC of any clinical setting. CONCLUSIONS Atrophic kidney at the end-stage of renal failure and under dialysis have lesions of ACDK that might predispose to RCC in dialysis and transplant patients.

Catheterized Urine Cytology of Mucinous Carcinoma Arising in the Renal Pelvis

BACKGROUND Primary mucinous carcinoma of the renal pelvis is a rare tumor; therefore, criteria for cytologic diagnosis of this tumor have not been established. CASE An 81-year-old woman suffered from macrohematuria for six months and was found to have a tumor in the right kidney by radiographic examination. Catheterized urine obtained from the right renal ureter was viscous and contained spherical clusters of cells with occasionally vacuolated, lacy and basophilic cytoplasm. In the small to medium-sized nuclei, chromatin was coarse and granular, and the nuclear membrane was thin and nearly smooth. Large nucleoli were evident in some of the nuclei. These findings were consistent with adenocarcinoma possibly of mucinous type. CONCLUSION Preoperative diagnosis of mucinous carcinoma is possible by cytologic findings of catheterized urine together with clinical data.

Voided Urine Cytology of Papillary Renal Cell Carcinoma and Renal Calculus

BACKGROUND Preoperative diagnosis of cases of renal calculus complicated with papillary renal cell carcinoma (RCC) by image analysis is usually difficult. CASE A 50-year-old man who had a past history of renal calculus suffered from macrohematuria and abdominal pain for one month was admitted to our hospital. Ultrasonographic examination revealed a 4-cm tumor shadow in the right kidney; it was hypovascular in arteriography. Papillary cell clusters with abundant cytoplasm were found by the cytologic examination of voided urine. Their nuclei were oval and situated eccentrically in the cytoplasm. The nuclear/cytoplasmic ratio was increased. Fine, granular chromatin was distributed evenly, and the nuclear membrane was thin and nearly smooth. Several small nucleoli were evident. All these findings were indicative of a diagnosis of papillary RCC. Histology of nephrectomy specimens confirmed the diagnosis. CONCLUSION Voided urine cytology can be useful for screening and follow-up of patients with papillary RCC.

A case of breast cancer diagnosed by inguinal lymph node metastasis.

We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a Tl tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes.

Studies on Cerebral Lipidosis Prenatal Diagnosis of Tay‐Sachs Disease*

In the attempt to diagnose TSD, amniotic fluid was obtained by amniocentesis in a mother whose first child was TSD. Amniotic fluid and uncultured amniotic cells showed absence of hexosaminidase A. The fetus was diagnosed as TSD and the pregnancy was terminated through artificial abortion. Hexosaminidase A in the fetal brain and liver was deficient and an increase of ganglioside Gm2 was observed in the brain of the affected fetus.