Tsutomu Kasuga

Coronary artery lesions in Takayasu arteritis: Pathological considerations

SummaryThis communication reviews the clinical and pathological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed.

Neoplastic angioendotheliosis. Immunohistochemical and electron microscopic findings in three cases

Three cases of neoplastic angioendotheliosis (NAE) presenting with central nervous system (CNS) disease but no skin lesions are described. The histogenesis of the neoplastic cells is discussed. Microscopic examination showed accumulation of neoplastic cells in the vascular system throughout the body and their extravascular proliferation in several organs. Electron microscopic and immunohistochemical studies revealed the presence of Weibel‐Palade bodies and factor VIII‐related antigen in intravascular and extravascular neoplastic cells in two of the three cases. In the first case the neoplastic cells did not have any T‐cell markers. However, in one case no specific markers were found in the neoplastic cells by electron microscopic, enzyme histochemical, or immunohistochemical examination. These findings, although supporting the endothelial origin of the neoplastic cells, indicate the need for further consideration of whether NAE is actually a single disease entity or several different diseases.

Tumor-Promoting Effects of Both Iodine Deficiency and Iodine Excess in the Rat Thyroid

Thyroid tumor-promoting effects of iodine deficiency and iodine excess were investigated in a rodent 2-stage model to estimate an optimal iodine intake range that would not effectively promote development of thyroid neoplasia. Six-week-old male F344 rats were given a single subcutaneous injection of 2,800 mg/kg body weight N-bis(2-hydroxypropyl)-nitrosamine (DHPN) or saline vehicle, maintained on Remingtons iodine-deficient diet (21 ± 2 ng/g iodide), and supplemented with various amounts of potassium iodide up to 260 mg/liter in drinking water to generate conditions ranging from severe iodine deficiency to severe iodine excess. In DHPN-treated rats, both conditions significantly increased thyroid follicular tumorigenesis. In DHPN-untreated rats, iodine deficiency produced diffuse thyroid hyperplasia, characterized by small follicles with tall epithelium and reduced colloid, together with a decrease in thyroxine (T4) and an increase in thyroid-stimulating hormone (TSH). On the other hand, iodine excess produced colloid goiter, characterized by large follicles with flat epithelium and abundant colloid admixed with normal or small-sized follicles lined by cpithelium of normal height, together with normal serum T4 and slightly decreased TSH. These effects were directly proportional to the severity of iodine deficiency or extent of iodine excess and suggest that each condition has a different thyroid tumor promotion mechanism. Iodine intakes that showed the least tumor promotion were 2.6 and 9.7 μg/rat/day in this study. Promoting mechanisms and the problem of statistically estimating recommended daily iodine intake range are briefly discussed.

Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation to histological subtypes of lung cancer

The incidence of atypical bronchioloalveolar cell hyperplasia (ABH) of the lung was investigated to evaluate the possiblity of this lesion being a precancerous stage in the histogenesis of adenocarcinoma. Lobectomy and pneumonectomy specimens of 165 primary and 45 metastatic tumour cases were step-sectioned horizontally and examined histologically. An average of 51 blocks were taken in each case. Sixty-seven ABHs up to 10 mm in diameter were detected, only 2 lesions being associated with scar tissue. Age was one factor apparently related to ABH development, although not the major one. There was no correlation between smoking index and ABH occurrence. In males, the incidence was highest in association with adenocarcinoma (25.5% of cases, 0.8% of sections), followed by large cell carcinoma (25.0% of cases), squamous cell carcinoma (10.5% of cases) and metastatic tumours from other sites (4.8% of cases). In females, ABH was also more common together with adenocarcinoma (8.3% of cases) than with metastatic tumours (4.0% of cases). The differences in male incidences by case and by section between the adenocarcinoma and metastatic tumour categories were statistically significant (P<0.05,P<0.01 respectively) indicating that ABH may be a precancerous lesion capable of transformation of adenocarcinoma.

Melanocytes and melanosis of the oesophagus in Japanese subjects--analysis of factors effecting their increase.

Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.

Angiosarcoma of the scalp : Report of two cases with fatal pulmonary complications and a review of Japanese autopsy registry data

Two cases of angiosarcoma of the scalp were reported. The patients were elderly men and died from pulmonary complications, including pneumothorax, pulmonary haemorrhage and pneumonia, associated with metastatic tumours in the lungs. The data recorded from 95 autopsies of patients with angiosarcoma in Japan during 1980–1984 were analyzed. According to the anatomical distribution of the primary tumour, the patients could be subdivided into a scalp group and non-scalp group. In both groups, the most common metastatic site was the lung. The patients of the scalp group had more frequent pulmonary complications such as pneumonia, haemothorax, atelectasis and pneumothorax, when compared with the patients of the non-scalp group. In particular, pneumothorax was observed only in the patients of angiosarcoma of the scalp. The results indicate that angiosarcoma of the scalp tends to metastasize to the lung, especially to the subpleural or surface pleural area, and these metastatic tumours are prone to necrosis, causing characteristic pulmonary complications.

MUCOEPIDERMOID CARCINOMA OF THE THYMIC REGION

A case of mucoepidermold carcinoma in thymus in a 59‐year‐old Japanese female is presented. She died of cardiac tamponade due to tumor invasion after a 5 years clinical course. At autopsy the main tumor was found in the thymic region with metastases to the sternum, regional lymph nodes, pericardial, and left pleural cavity. The mucoepidermold carcinoma might be probably originated from a hens egg‐sized cyst which was located in the upper posterior aspect of the tumor‐Involved thymus. No teratomatous components were present. The cyst was most likely to be of thymic or bronchogenic cyst origin, though it was not determined, in view of the lining with pseudo‐stratified ciliated columnar epithelium of the cystic wall and the surrounding with the thymic tissue outside. Moreover, there was thymic hyperplasia with germinal center that was compatible with SLE‐like symptoms in her past history and autoimmune nature of the autopsy findings of pulmonary fibrosis.

Association of Sjögren's syndrome with pulmonary hypertension: report of two cases and review of the literature.

We report two autopsy cases of Sjögrens syndrome associated with pulmonary hypertension. The pulmonary muscular arteries of both cases showed concentric fibrocellular intimal proliferation, medial hypertrophy, and plexiform lesions. To determine the significance and pathogenesis of this rare association, we carried out morphometric and immunofluorescent studies and reviewed the seven similar cases reported in the literature. Depositions of immunoglobulin G, Clq, C3c, C4, and C5 were observed in the pulmonary arterial walls of both of our cases. Morphometric studies revealed increased medial thickness to radius ratios and intimal thickness to radius ratios of the pulmonary muscular arteries in both cases. Previously reported patients were all female, and those cases were frequently associated with Raynauds phenomenon. This report provides additional and convincing evidence for an association of Sjögrens syndrome and plexogenic pulmonary hypertension based on a detailed study of two cases and a review of the literature. The significance and pathogenesis of this association were examined, but not clarified. However, our studies add to the accumulating data suggesting a link between autoimmune diseases and chronic pulmonary hypertension.

Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia

SummaryBone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for biastic proliferation.

Malignant Clear Cell “Sugar” Tumor of the Kidney: Clear Cell Variant of Epithelioid Angiomyolipoma

Angiomyolipoma is a heterogeneous proliferation composed of an admixture of blood vessels, smooth muscle cells, adipocytes and peculiar myoid cells with variable melanin synthesis. Epithelioid angiomyolipoma, which often has malignant potential, has been reported previously.1 Recently clear cell “sugar” tumor has been described as a clear cell variant of epithelioid angiomyolipoma.2 Clear cell “sugar” tumor or epithelioid angiomyolipoma of the kidney is microscopically similar to renal cell carcinoma and, therefore, differential diagnosis is often difficult.2 However, the habitual presence of melanosomes in these lesions is significant and distinguishes them from renal cell carcinoma.1 We report a case of clear cell “sugar” tumor that consisted of pigmented clear cells resembling renal cell carcinoma. CASE REPORT A 23-year-old woman presented with left abdominal pain. The patient had no history of tuberous sclerosis. Ultrasonography and computerized tomography demonstrated a 10 9 cm. tumor in the left kidney and retroperitoneal lymph node swelling (fig. 1). Left nephrectomy and retroperitoneal lymph node dissection were performed. Macroscopic finding was an expansive tan colored renal tumor. The tumor was made up of clear cells with scattered sarcomatoid features, and some cells contained intracytoplasmic brown pigment. Immunohistochemically the expression of HMB-45, melanosome associated protein, was positive although other immunostains, including epithelial markers (epithelial membranous antigen and cytokeratin), vimentin and S-100, were negative (fig. 2). The melanosomes were detected via electron microscopy.