Yoshinori Urano

Yolk sac tumor (endodermal sinus tumor) and alpha-fetoprotein. A report of three cases.

Three instances of malignant teratomas with positive reaction for alpha‐fetoprotein (AFP) are presented. Sequential evaluations in them revealed that the production rate of AFP closely paralleled the amount of the viable malignant tumor tissue which fluctuated in the course of the diseases. Two of these tumors originated in the testis and a third in the presacral region. The microscopic sections of these malignant teratomas were carefully reviewed and it was concluded that they are properly classified as yolk sac tumor or endodermal sinus tumor. The occurrence of AFP in these tumors is best explained by the yolk sac notion, because it is known that large amounts of AFP are synthesized not only by the fetal liver, but also by the yolk sac at early embryogenesis. This phenomenon will conversely lend an additional support to the morphologic contention that these tumors are of yolk sac origin and deserves further investigation.

Alpha-fetoprotein, prealbumin, albumin, alpha-l-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.

A study on alpha-fetoprotein and endodermal sinus tumor

Abstract The phenomenon of alpha-fetoprotein production by testicular, ovarian, or sacrococcygeal teratocarcinomas is frequently observed but has not been well explained. This paper includes clinicopathologic studies of 19 cases of teratocarcinoma with positive AFP reactions. Sixteen of the 19 showed typical histologic features of endodermal sinus tumor (yolk sac tumor) of Teilum and one other was compatible with this diagnosis. 6,7 The occurrence of AFP in these tumors is best explained by the concept of endodermal sinus tumor; because it is known that large amounts of AFP are synthesized not only by the fetal liver but also by the yolk sac during early embryonic life, and because the diagnosis of endodermal sinus tumor itself implies that the tumor is of yolk sac origin morphologically. 13 More direct evidence of AFP synthesis was demonstrated by immunofluorescent technique in one of our cases. Immunofluorescence was seen only in that cell layer long defined as of yolk sac origin morphologically. Alpha-fetoprotein studies are valuable in following such patients, unless they are 1 mo of age or younger.

α-FETOPROTEIN IN YOLK SAC TUMOR

Although the a-fetoprotein ( A F P ) concentration is most frequently elevated in the serum of patients with hepatocellular carcinoma, as many as 62% of patients wth teratocarcinoma have been found to have abnormally high serum A F P concentrations.1 In 1967, Abelev and his co-workers 2 first reported that A F P was positive in 13 of 32 cases with testicular teratoblastoma and the rate of the positivity higher in those with the features of embryonal carcinomas.3 Masopust and his associates published a paper in 1968 stating that A F P was found in the sera of patients with ovarian, testicular, and presacral teratocarcinomas. Thereafter, more than 50 AFP-positive teratocarcinomas, originating in various sites including the ovary, testis, and the sacrococcygeal, mediastinal,: and intracranial ti regions, have been reported up to now, and many of the authors”’ have observed that determination of serum A F P concentrations reflected not only the progress of the illness but also the effectiveness of therapy, as it does frequently in hepatocellular carcinomas. The occurrence of the AFP in hepatocellular carcinomas and in some hepatic disorders has been well explained in connection with the synthesis of this protein by the fetal liver. However, the phenomenon of A F P synthesis by teratocarcinomas has not been well explained until recently. Specifically, unsolved questions have been ( I ) whether all malignant teratomas are AFPpositive and all benign teratomas AFP-negative, ( 2 ) why A F P is positive in teratocarcinomas, and (3) which part of the tumor tissue of teratocarcinoma synthesizes AFP. Concerning the second question mentioned above, the authors reported in 1973 three cases of AFP-positive teratocarcinomas that were originally classified as embryonal carcinoma * I but reclassified as yolk sac tumor (endodermal sinus tumor) after reexamination.!’ They pointed out that the occurrence of A F P in teratocarcinomas is best explained by the concept of a yolk sac tumor, because a yolk sac tumor (endodermal sinus tumor) is of yolk sac origin by definition, l 3 and because it is known that large amounts of A F P are synthesized by the fetal yolk sac as well as by the fetal liver.ll-lk The same explanation has been given independently by Ballas in 1972,l!’ and Wilkinson et al. in 1973.”’ To confirm this explanation, it was necessary to review a much larger series of AFP-positive teratocarcinomas with the concept of yolk sac tumor in mind.!’ I t is especially important to know which part of the tumor tissue of teratocarcinoma produces AFP, but there have been only a few works 2 1 4 3 that demonstrated immunofluorescent localization of A F P in teratocarcinomas since the first report by Mawas and his colleagues in l969.?’ This paper consists of a survey of A F P incidence in benign and malignant

RHABDOMYOSARCOMA WITH BONE MARROW METASTASIS SIMULATING ACUTE LEUKEMIA

Rhabdomyosarcoma manifested as a systemic disease is very rare and cases showing diffuse metastasis in the bone marrow are most unusual. Recently we encountered two cases of rhabdomyosarcoma with diffuse bone marrow metastasis which were clinically manifested as acute leukemia. The first patient was a 15‐year‐old female, who was admitted in 1982 with pancytopenia and many large primitive cells in bone marrow aspirates, hematological malignancy being diagnosed. Thereafter the bilateral breasts showed rapid swelling and a biopsy specimen revealed the histological features of typical alveolar rhabdomyosarcoma. The primary site of the neoplasm remained undetermined during the course. At autopsy, it was disclosed that the neoplasm originated from the left thigh and showed generalized metastasis. The second patient was a 38‐year‐old man, who was admitted in 1986 because of a nasal polyp obstructing the nasal cavity, and persistent nasal bleeding. Peripheral blood samples showed leucoerythroblastosis and thrombocytopenia, and large primitive cells were found In bone marrow aspirates, so that hematological malignancy was initially diagnosed. A biopsy specimen of the nasal polyp showed proliferation of large round cells and electron microscopy demonstrated the ultrastructural features of rhabdomyosarcoma.

Arteriovenous malformation of the spinal cord. Three-dimensional reconstruction of the intramedullary abnormal vessels.

We report a case of spinal arteriovenous malformation (AVM) in which detailed morphological examination of the intramedullary vascular lesion was carried out employing serial section studies. The relationship of the malformation to parenchymal lesions was evaluated. An abnormal vessel at the spinomedullary transition, whose lamina elastica was partially interrupted, was suggestive of a shunt vessel. The location of the intramedullary abnormal vessels and foci of softening of the spinal cord almost overlapped in distribution. Three-dimensional reconstruction of the intramedullary abnormal vessels demonstrated marked elongation and tortuosity of the original vascular architecture and they ended in the extramedullary abnormal vessels with thickened wall. Thus, our study showed that the intramedullary abnormal vessels were the result of secondary changes subsequent to pressure and volume overload inflicted upon the spinal venous system through AVM. Compression by tortuous elongation of the intramedullary vessels is the apparent cause of the parenchymal softening. A traumatic factor in the aetiology of the AVM was also discussed, since the patient had had two preceding episodes of traffic accidents with cranial and lumbar injury. Trauma seemed to be significant factor as a trigger of symptoms.

RENAL CELL CARCINOMA ORIGINATING FROM DYSPLASTIC KIDNEY

A case of renal cell carcinoma developing from a unilateral dysplastic kidney is presented. The patient was a 33‐year‐old woman who had lumbago one year and a half prior to death. Multiple abnormal uptakes of 67Ga were seen by scintigraphy. Bone marrow biopsy indicated adenocarcinoma but the primary site was unknown despite extensive examination. At autopsy the carcinoma was wide‐spread but no obvious primary‐appearing lesion was detected in all the organs except the left kidney. Incidentally the patient had unilateral (left) renal dysplasia. An elaborate study revealed the primary site of the carcinoma within the cystic structure of the dysplastic kidney. This tumor showed reactivity with Dolichos biflorus agglutinin associated antigen (DBA‐Ag), soybean agglutinin (SBA), and peanut agglutinin (PNA) which have reactivity with renal tubules.

Spinocerebellar degeneration with prominent involvement of the motor neuron system: autopsy report of a sporadic case

SummaryA sporadic case of spinocerebellar degeneration with prominent involvement of the motor neuron system is reported. A Japanese male without contributing family history, developed cerebellar ataxia at the age of 52, followed by generalized amyotrophy and ophthalmoplegia, and died aged 58. The clinical findings were pathologically verified as degeneration of the spino-ponto-cerebellar system and the motor neuron system, the latter almost identical to those of amyotrophic lateral sclerosis. Additional subclinical changes were found in the dentate nucleus and substantia nigra. Brain-stem nuclei subserving eye movements were well preserved, suggesting a supranuclear basis for the ophthalmoplegia. This unusual combination of system degenerations has on rare occasions been reported in the heredofamilial cerebellar disorders. As a sporadic case, however, this may be the first autopsy case of spinocerebellar degeneration with severe concurrent involvement of the motor neuron system.

AN AUTOPSY STUDY OF LUNG CANCER IN UNIVERSITY OF TOKYO FOR THE LAST 27 YEARS, FROM 1958 TO 1984, WITH SPECIAL REFERENCE TO THE CHARACTERISTICS OF LUNG CANCER IN JAPAN

Four hundred and sixty‐five male and 159 female consecutive autopsy cases of lung cancer, autopsied over the 27 years from 1958 to 1984, were analysed and were compared with other materials and mortality statistics, including statistics from other countries. Malignant tumor autopsy cases are gradually increasing and now comprise more than 60% of total autopsy cases. The percentage of lung cancer cases among all autopsy cases was 7% in males and 4% in females. The percentage of lung cancer in autopsies of patients with malignancies was about 13% for males and 9% for females. The most frequent fatal malignant tumors were gastric cancer, lung cancer, and leukemia. The relative incidence of gastric cancer was decreasing, while that of lung cancer was increasing. In the distribution of the histological types of lung cancer, adenocarcinomas were the most frequent types in both sexes. As has been noted in mortality statistics, we noticed a gradual shift in the peak age of lung cancer autopsy cases towards older patients. During the period under study, the peak shifted from patients in their sixties to patient in their seventies; this was true for most of the major histological types in both sexes. The male/ female ratio of all lung cancer cases was 2.9, which was much lower than the ratio found in the United States and Europe, and very similar to the ratio of the mortality rates in Japan and other Asian countries. It was pointed out that the male/female ratios by age‐group in each country is a very good reflection of the histological distribution.

GIANT MESENTERIC LYMPHOID TUMOR (CASTLEMAN'S LYMPHOMA) - A CASE REPORT

An autopsy case of a giant mesenteric lymphoid tumor in a 57‐year‐old female was examined anatomo‐biologically. A 17x15x6 cm3‐sized pinkish gray‐coloured medullary tumor occupying the mesenterium with no evident capsule, invaded the small intestine and pancrease head. Histologically, it was a lymphoid tissue consisting of hyalinized angio‐follicular architecture having epithelioid cells and tingible body macrophages in the follicles. Some small‐sized follicles showed typical Hassalloid architecture and other follicles consisted of monotonous growth of lymphocytes without a mantle zone, some of them fusing with each other. The histopathological appearance of the tumor was that of Castlemans lymphoma and of hyaline‐vascular type of Kellers Classification.13 There was another 0.6x0.5x0.5 cm3‐sized tumor having an angiofollicular architecture in the subserosa of the sigmoid colon. The present case was complicated with vertebral caries, hypogammaglobulinemia (1.2%), eosinophilia (50%) and panbronchobronchiolitis, the last one being responsible for her death.