Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators.

Patients with amyotrophic lateral sclerosis (ALS), who survive longer on a life-support system, exceeding the natural course of this disease, show new features of ALS. We report here a clinico-pathologic study of a 51-year-old patient with sporadic ALS who developed progressive external ophthalmoplegia 3 years after he remained on a respirator and died 5 years later, 13 years after the onset of his illness. The external ophthalmoplegia was initially accompanied by preserved doll's eye phenomenon, which later became absent. Autopsy revealed not only degeneration of the upper and lower motor neuron systems typical of ALS, but also degeneration of the Clarke's dorsal nuclei, spinocerebellar tracts, substantia nigra and inferior olives in addition to intracytoplasmic neuronal inclusion bodies in various areas. The oculomotor and abducens nuclei were variably involved, accompanied by neurogenic atrophy of the extraocular muscles. Our case report is consistent with the idea that ALS comprises a heterogeneous group of disorders, and also indicates that long-term use of respirators may make some patients with this illness prone to developing atypical clinical and neuropathologic features which are not observed during the natural course of ALS.

Bone metastasis from colorectal cancer in autopsy cases.

The incidence of bone metastasis from colorectal cancer is reported to be 10.7% in autopsy cases. However, the characteristics of the primary cancers, as well as the patterns of bone metastasis, remain unclear. We analyzed the clinical and autopsy records of 118 patients with primary colorectal cancer treated either surgically or conservatively and eventually autopsied between 1970 and 1987 at Toranomon Hospital in Tokyo. Bone metastasis was detected in 23.7% (28/118). The average age of patients with bone metastasis was lower than that in patients without bone metastasis (P < 0.02). Cancers to the rectum and cecum were accompanied by bone metastasis more frequently than cancers of other portions of the colon. Signet-ring cell carcinoma showed a high incidence of bone metastasis (P = 0.041). Bone metastasis from colorectal cancer was associated with liver or lung metastases (P < 0.0001). These results indicated that bone metastasis from colorectal cancer is not as infrequent as previously described.

Enterogenous cyst of the cerebellopontine angle cistern: case report.

A case of an enterogenous cyst located in the cerebellopontine angle cistern is presented. These cysts have usually been found in the spinal canal, and their intracranial occurrence is exceptional. In the present case, the cyst was lined histologically by a single epithelial layer of cuboidal cells with some glandular structures resembling the fundic glands of the stomach. The unusual location of the cyst and its histological features are discussed.

Calcified intracranial metastatic tumor mimicking meningioma--case report.

A 60-year-old female presented with mild cerebellar dysfunction due to a calcified tumor attached to the undersurface of the tentorium cerebelli demonstrated by cranial computed tomography, and a lung mass on a chest x-ray film. The calcified nature and location made preoperative differentiation between metastatic brain tumor and meningioma difficult. Operation subsequently revealed that the brain tumor was a metastasis from lung adenocarcinoma. Metastatic brain tumors can be calcified, and should be considered in the differential diagnosis of calcified intracranial lesions.

Primary intracranial amelanotic melanoma--report of an autopsy case.

Primary intracranial amelanotic melanoma was verified at autopsy in a 38-year-old male. Correct diagnosis of amelanotic melanoma needs electron microscopy or immunohistochemistry, since Masson staining is negative due to the absence of melanin pigment. We adopted the following criteria for clinical use: macroscopically not dark and microscopically negative for Masson staining, but ultrastructurally various melanoma types present. Although the clinical profile of this case is consistent with melanotic melanoma, the more detailed features of primary intracranial amelanotic melanoma require future study.

[An autopsy-verified case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180 point mutation].

An autopsied case of Creutzfeldt-Jakob disease is reported. A 79-year-old Japanese female showed extrapyramidal sign (resting tremor, and rigidity) and dementia. She developed myoclonus and became akinetic within one year from the onset, and then died of pneumonia at age of 81. None of the members of her family had neuromuscular disorders. CT and MRI studies revealed progressive brain atrophy. Consecutive study of EEG did not reveal periodic synchronous discharges (PSD). Codon 129 polymorphism (Met/Val) and codon 180 point mutation (Val/Ile) were detected. The autopsy revealed spongiform change of cerebral cortex and negative Kuru plaques, confirming the diagnosis of Creutzfeldt-Jakob disease. Immunohistochemical study revealed weak synaptic prion staining. Western blot analysis showed positive Proteinase K resistant prion protein. Gene analysis of autopsied brain showed the same prion DNA polymorphism and mutation. The combination of codon 129 polymorphism and 180 point mutation might associate with an atypical clinical form of CJD, which shows the extrapyramidal signs at the onset, and negative PSD in EEG.

Cancer of the gastric cardia and the habit of smoking.

The habits of smoking and drinking were investigated in relation to pathologic findings in the stomachs of 1,347 patients who had undergone surgery for gastric cancer at Toranomon Hospital between 1977 and 1986. There were 1,210 patients (807 males and 403 females) with single gastric cancer and 137 (117 males and 20 females) with multiple gastric cancer. The most frequent location of the tumor in cases of single gastric cancer was the middle third (47.8%), followed by the distal third (33.4%), upper third (13.1%) and cardiac region (5.7%). Tobacco consumption was positively associated with gastric cancer in males (odds ratio as the approximate relative risk = 2.8), whereas alcohol consumption was not. Neither tobacco nor alcohol consumption was positively associated with gastric cancer in females. Among male patients with single cancer, the habit of smoking was more prevalent in those with cancer of the cardia than in those with cancer of other portions of the stomach (p less than 0.01).

[Evaluation of autopsy cases in pancreatic cancer].

The incidence of pancreatic cancer has increased recently. The average age of pancreatic cancer patients in our series was 60.6 years; the male to female ratio was 2.3:1. As for tumor location, the head (45.5%) was the most frequent followed by the body (32.7%) and the tail (20%). Pancreatic cancers were histologically classified as duct carcinoma (88.2%), acinar cell carcinoma (0.9%), islet cell carcinoma (1.8%) and undifferentiated carcinoma (9.1%). In 17 cases (15.5%), diabetes mellitus was an accompanying complication.

The role of the biopsy in diagnosis of early gastric cancer.

In order to determine the reliability of endoscopic biopsy in diagnosis of early gastric cancer, and to clarify the problems with biopsies, preoperative endoscopic biopsies from 771 early gastric cancer cases were reviewed and analyzed clinicopathologically in comparison with surgically resected specimens. The 771 cancers were surgically resected at the National Cancer Center Hospital during the period from 1972 to 1982. Definite histological diagnosis was obtained in 87.4% of the carcinomas at the initial biopsies. Repeated biopsy raised the percentage of correct definite diagnoses to 96.1%. False-negative (including suspicion of cancer) diagnosis was most frequent in the case of depressed lesions (50 lesions). Half of the false negatives were found to be due to sampling errors by the endoscopists. The other half of these 50 lesions were diagnosed as "suspicious of malignancy" because of the histological difficulty in differentiating early gastric cancer from regenerative atypia with intestinal metaplasia, or because there was not enough information, or for the other reasons. Most of the 31 false-negative diagnoses at the initial biopsy from elevated lesions were reported as adenoma (group III) or suspicious of carcinoma (group IV), indicating that differential diagnosis between well-differentiated adenocarcinoma and adenoma is very difficult. The result of the present study suggests that repeated biopsy from correct sites and discussion of the lesions between clinicians and pathologists are very important.

Seroconversion from HBs-Ag to anti-HBs in a case of liver cirrhosis associated with hepatocellular carcinoma.

This paper reports a case of liver cirrhosis associated with hepatocellular carcinoma (HCC) of a woman who was converted from hepatitis B surface antigen (HBs-Ag) positive to antibody against HBs-Ag (anti-HBs) positive in the serum through an immunoregulatory steroid rebound phenomenon. The histology of the biopsy specimen taken before the seroconversion showed an early stage of liver cirrhosis with moderate infiltration of mononuclear cells. At autopsy about 3 years after the seroconversion, the liver tissue free of the tumor was in an early stage of liver cirrhosis. Fibrosis did not advance as compared with the biopsy specimen. In addition, mononuclear cell infiltration decreased remarkably and piecemeal necrosis disappeared after the seroconversion. The immunohistologic examination of hepatocytes demonstrated that positive stainings for HBs-Ag and for hepatitis B core antigen (HBc-Ag) in the biopsy specimen turned to be negative in the autopsy specimen. These facts indicate that the steroid rebound phenomenon eliminated free hepatitis B virus (HBV) in the hepatocytes in the absence of massive necrosis of hepatocytes. HBV-DNA integration was proved in the genome of HCC by molecular hybridization method.

Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C.

Hepatitis C virus RNA as detected by reverse transcription and nested polymerase chain reaction was monitored in 16 patients with chronic hepatitis C treated with interferon. Hepatitis C virus RNA became undetectable after 4 to 8 wk of interferon administration in 13 of the 16 patients. During 6 mo of follow-up, 5 of the 13 patients who became negative for hepatitis C virus RNA after interferon administration remained negative, and all five continued to have normal ALT levels. Repeat liver biopsy in these five patients revealed histological improvement. Antibody to hepatitis C virus, which was initially positive in all treated patients, fell to undetectable levels in three of the five patients. In contrast, aminotransferase levels rose again in all eight patients who had become hepatitis C virus RNA negative but had again exhibited hepatitis C virus RNA after completion of therapy. In 16 untreated patients, hepatitis C virus RNA remained detectable. These results indicate that detection of hepatitis C virus RNA may be useful as a marker of viral replication in chronic hepatitis C; they also suggest that interferon should again be administered to patients who become hepatitis C virus RNA negative on treatment but again exhibit this marker of viral replication when treatment is stopped.