Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy

We investigated the presence of anti-human T-lymphotropic virus type I (HTLV-I) IgM in sera and cerebrospinal fluid from patients with HTLV-I-associated myelopathy (HAM) by Western blot analysis. Analyses of 36 serum samples revealed that most patients (31/36; 86.1%) had anti-HTLV-I IgM, whereas only four of 23 (17.4%) HTLV-I carriers had it. In studies of cerebrospinal fluid, anti-HTLV-I IgM was detected in 24 of 36 (66.7%) HAM patients, whereas none was detected in nine HTLV-I carriers. The differences were statistically significant (p less than 0.01). These results suggest that persistent active replication of HTLV-I occurs in the central nervous system as well as in the peripheral blood of HAM patients, and may contribute to the development of HAM.     

Case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain]

We reported a case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain and lungs. A 21-year-old man was admitted because of one month history of low grade fever, headache, nausea, and amnesia. He developed agammaglobulinemia following Epstein-Barr virus infection at 3-year-old, and thereafter was administered 7.5g of immunoglobulin every 3 weeks with a diagnosis of XLP. Physical examination was unremarkable on admission. Neurological examination revealed disorientation of time, and bilateral gaze-evoked nystagmus. Neuropsychological tests demonstrated impairment of recent memory and calculation. Pleocytosis (83/microl) and increase of protein (1269 mg/dl) and IgG (141 mg/dl) in the CSF were observed. Brain MRI showed multiple nodular lesions with high intense signal on T2-weighted images and Gd-DTPA enhancement on T1-weighted images. Chest CT showed multiple nodular lesions in the bilateral lungs. The needle lung biopsy was performed, which showed infiltration of lymphocytes around the vessels. An immunohistochemical study showed that the infiltrating cells were mainly CD8 positive T lymphocytes. B lymphocyte and plasma cells were not seen. The histological findings excluded intravascular malignant lymphoma and lymphomatoid granulomatosis. Therefore we diagnosed lymphoid vasculitis. The patient developed pancytopenia caused by hemophagocytic syndrome 48 days after admission and was treated with 1 g of methylprednisolone per day for 3 days and a tapered dose of steroid (500 mg to 125 mg of methylprednisolone and 60 mg to 10mg of predonisolone) for 21 days, which resulted in the improvement of clinical features (hemophagocytic syndrome and central nervous system symptoms) and the abnormal CSF findings. The multple nodular lesions in the brain and the lungs shrank 1 month after treatment and disappeared 11 months later. There are few reports concerning lymphoid vasculitis with XLP, and no effective treatment has been described. Our case suggests that steroid therapy may be useful for the treatment of lymphoid vasculitis in XLP.     

Cross-cultural validation of the Japanese version of the lung cancer subscale on the functional assessment of cancer therapy-lung.

BACKGROUND: The Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, which consists of a core questionnaire (the General Measure of FACT [FACT-G]) and a 9-item Additional Concerns comprised of a 7-item Lung Cancer Subscale (LCS), was developed in an English-speaking culture. The validation of the Japanese FACT-G was reported previously, and this report describes the cross-cultural validation of the LCS. METHODS: The Japanese version of the LCS was developed through an iterative forward-backward translation sequence used throughout the FACT Multilingual Translation Project. In evaluating psychometric performance, its construct validity was investigated with Cronbach's alpha coefficient and factor analysis. Clinical validities of a known-groups comparison and longitudinal validity were also investigated. RESULTS: The FACT-L was administered twice to 180 patients with lung cancer within 2 weeks. The Japanese LCS had borderline values for Cronbachs alpha coefficients (0.62-0.67). Factor analysis indicated that the LCS had the three dimensions of respiratory symptoms, appetite plus body weight, and clear thinking. For clinical validity, a known-groups comparison showed that the LCS could differentiate patients according to truth disclosure, as Japanese doctors sometimes do not fully inform terminally ill patients. However, responsiveness was not proved when performance status was used as an anchor, probably owing to the short interval between the administration of the two measures. CONCLUSION: The Japanese version of the LCS asked questions about multiple symptoms of patients with lung cancer, as did the original English LCS. The longitudinal clinical validity of the Japanese version should be investigated in future clinical trials.     

Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines

In a previous study, we used a murine monoclonal antibody, A7, against human colon carcinoma as a drug-carrier to treat colorectal cancer.¹ In the present study, we found that MAb A7 also reacted immunohistochemically with 73% of human pancreatic carcinoma cell lines, with the A7 antigen mainly being detected on the cell surface. However, the A7 antigen was found in only 9% of the spent media of these human pancreatic carcinoma cell lines by ELISA. On the other hand, the positive incidence of CA19-9, POA, ferritin, CEA, DU-PAN-2 and SLX in those spent media was 100%, 64%, 64%, 55%, 55% and 36%, respectively. These results suggest that the A7 antigen may only rarely be shed into the sera of pancreatic cancer patients, in which case MAb A7 could be a suitable drug-carrier in targeting chemotherapy for pancreatic cancer patients.     

Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease]

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.     

Primary leiomyosarcoma of the thyroid gland

Primary leiomyosarcoma of the thyroid gland is extremely rare, and to the best of our knowledge only five well-documented cases have been reported in the world literature. We herein report a 58-year-old female patient with primary leiomyosarcoma of the thyroid who was successfully treated by total thyroidectomy with a modified neck dissection. Immunohistochemically, the tumor cells showed positive reactivity to α-smooth muscle actin and vimentin. Radical surgery was thus considered to be essential in the treatment of this rare but rather aggressive malignancy.     

A Case of Glucagonoma with Liver Metastasis: Complete Response to Dacarbazine

Abstract: We report a case of glucagonoma syndrome with liver metastasis, who responded completely to dacarbazine chemotherapy. A 77-year-old woman complained of itching skin eruptions (diagnosed as necrolytic migratory erythema) and weight loss. She was found to have glucose intolerance, anemia, hypoproteinemia and hyperglucagonemia. Abdominal CT and celiac arteriography showed a hypervascular tumor in the pancreatic tail and a metastatic tumor in the left hepatic lobe. Immunohistochemical examination of the metastatic liver tumor obtained by laparoscopic biopsy revealed the tumor cells to be positive for glucagon. The patient was treated with 20 courses of 300 mg/day intravenous dacarbazine for 5 consecutive days followed by a 4 week drug-free interval. No major side effects were noted. Treatment resulted in disappearance of the skin lesions and correction of anemia, glucose intolerance, hypoproteinemia and hyperglucagonemia. Follow-up abdominal CT showed complete resolution of both the primary pancreatic tumor and the metastatic liver tumor. We suggest that dacarbazine be considered as the treatment of choice for metastatic glucagonoma.     

Familial occurrence of differentiated,nonmedullary thyroid carcinoma

Familial occurrence of differentiated, nonmedullary thyroid carcinoma in 23 patients from 11 families is reported. Five patients were male and 18 were female. The familial relationship of patients was parent and child in 12 cases from 6 families, and siblings in 11 cases from 5 families. Carcinoma of other organs was noted in other members in 8 families. Histological examination revealed 18 papillary, 2 follicular, and 2 anaplastic carcinomas (the 2 anaplastic carcinomas were considered to be transformed from preexisting differentiated carcinoma). In 1 case, the histological type was unknown. The average diameter of the primary lesion was 29.9 mm. Cervical lymph node metastasis was found in 77.8% and local recurrence in 28.6% of the patients. Solid and invasive growth was dominant. On HLA typing, phenotypes of B₇ and DR₁ were significantly redominant in familial patients compared with nonfamilial patients and normal Japanese. Moreover, the haplotype of B₇-C_w7-DR₁ was observed in 5 of 13 patients tested. It is suggested from these observations that some types of differentiated, nonmedullary thyroid carcinoma may show familial occurrence and that they may have common factors with regard to the genetic and immunologic basis of the disease.

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Resumen Se informa la ocurrencia familiar de carcinoma bien diferenciado, no medular, de tiroides en 23 pacientes provenientes de 11 familias, 5 hombres y 18 mujeres. La relación familiar fue padre e hijo en 12 casos de 6 familias, y hermanos en 11 casos de 5 familias. Se observé la presencia de carcinoma de otros órganos en otros miembros de 8 familias. El examen histopatológico reveló 18 carcinomas papilares, 2 foliculares, y 2 anaplásicos (los 2 fueron considerados como transformación de carcinomas diferenciados preexistentes). En un caso no fue conocido el tipo histológico. El diámetro promedio de la lesión primaria fue 29.9 mm. Se hallaron metástasis en ganglios cervicales en 77.8% de los pacientes y recurrencia local en 28.6%. El crecimiento sólido e invasivo apareció como característica dominante. En la tipificación HLA aparecieron como significativamente predominantes los fenotipos de B₇ y DR₁ en pacientes familiares en comparación con pacientes no familiares y japoneses normales. Por otra parte, el halotipo de B₇-C_W7-DR₁ fue observado en 5 de 13 pacientes investigados.Como resultado de estas observationes se sugiere que algunos tipos de carcinomas diferenciados, no medulares, pueden demostrar ocurrencia familiar y que pueden poseer factores comunes relacionados con las bases genéticas e inmunológicas de la enfermedad.

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Résumé On a étudié les caratéristiques du cancer de la thyroïde, dans sa variété différenciée non médullaire, survenu chez 23 patients provenant de 11 familles. Cinq patients étaient des hommes, 18 des femmes. La relation familiale était parent/enfant dans 12 cas provenant de 6 familles, et frère/soeur dans 11 cas provenant de 5 familles. Des membres de 8 autres familles présentaient un cancer d'un autre organe. Il y avait 18 cancers papillaires, 2 cancers folliculaires, et 2 cancers anaplasiques (on a considéré que les 2 cancers anaplasiques étaient des transformations à partir de cancers différenciés préexistants). Dans un cas, le type histologique était inconnu. Le diamètre moyen de la lésion primitive était de 29.9 mm. On a retrouvé des métastases ganglionnaires cervicales chez 77.8% des patients et une récidive locale chez 28.6%. Les tumeurs étaient principalement solides et invasives. Par rapport aux cancéreux non familiaux et à la population japonaise normale, il y avait plus de phénotypes B₇ et DR₁ au système HLA. L'haplotype B₇-C_W7-DR₁ était observé chez 5 des 13 patients testés.On suggère que certains types de cancer différenciés, non médullaires, ayant des facteurs communs génétiques et immunologiques, peuvent survenir dans une même famille.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.