Hisako Endo

Telomerase activity and telomere length in benign and malignant human thyroid tissues

Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P<0.006), respectively. Our findings suggest that change in telomerase activity and telomere length may be important for development of thyroid tumors.

Pathology of the human spinal ganglia in varicella-zoster virus infection.

SummarySpinal ganglia from a patient who died on the 6th day of varicella infection were examined by immunofluorescence and electron microscopy, and were compared with spinal ganglia from a patient dying on the 17th day of herpes zoster infection. In herpes zoster, typical intranuclear inclusion bodies were found in neurons, satellite cells and fibroblast-like cells of the ganglia, which contained numerous naked virus particles. In varicella, few changes were found by light microscopy but viral antigen was detected in a few neurons and satellite cells by immunofluorescence. Electron microscopy revealed scattered virus particles near the nuclear membrane of a neuron, satellite cells and capsular cells and enveloped particles in the cytoplasma of satellite cells. The particles in the nuclei were mostly naked virions with specific crescent-like inner-nuclear structure; those in the cytoplasm had complete and incomplete envelopes and showed pleomorphism. A “virus-like” intranuclear filament found in mononuclear cells in herpes zoster and a “plexiform vermicellar array” found in the nuclei of neurons in varicella are at present considered to be non-specific nuclear changes caused probably by viral infections.

Sebaceous Epithelial-myoepithelial Carcinoma of the Salivary Gland: Clinicopathologic and Immunohistochemical Analysis of 6 Cases of a New Histologic Variant

Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is an uncommon, low-grade malignant tumor. A recent report demonstrates sebaceous differentiation in this tumor even though its significance has never been documented as a precise histologic variant. Six cases of EMC exhibiting sebaceous differentiation (sebaceous EMC) of the parotid gland were analyzed for their clinicopathologic features and immunohistochemical characteristics. In addition, primary salivary sebaceous carcinomas were also examined for comparison. In our series, the incidence of sebaceous EMC was 0.2% among 3012 cases of parotid gland tumors and 14.3% of all EMC cases. The 6 patients comprised 2 men and 4 women, age ranging from 77 to 93 years (mean, 83.7 y). Neither cervical lymph node nor distant organ metastases were found in any cases of sebaceous EMC and no patients died of disease, though local recurrences developed in 1 patient. Conversely, cervical lymph node metastasis was detected in 2 of 3 patients with sebaceous carcinoma, 1 of whom died of disease at 12 months. Histologically, all 6 tumors had an area of sebaceous differentiation admixed with features of bilayered ductal structures typical of EMC. A component of sebaceous differentiation was distributed diffusely in 4 tumors and focally in 2. Cytologic atypia of sebaceous EMCs was lesser than that of sebaceous carcinomas. Immunohistochemically, putative myoepithelial markers such as α-smooth muscle actin, calponin, p63, cytokeratin 14, S-100 protein, and vimentin were highly expressed in sebaceous EMC. However, the expression of the latter 4 markers was also observed in primary sebaceous carcinomas, whereas these tumors were all negative for α-smooth muscle actin and calponin. Positive immunoreactivity for epithelial membrane antigen, adipophilin, and perilipin confirmed sebaceous differentiation in EMC. These results indicate that sebaceous EMC is a low-grade malignancy, similar to conventional EMC. Our data also suggest that immunohistochemical examination of specific myoepithelial markers is helpful in distinguishing sebaceous EMC from sebaceous carcinoma, which may occasionally be associated with an aggressive clinical course.

An immunohistochemical study of bronchial cells producing surfactant protein A in the developing human fetal lung

A study on immunohistochemical localization of pulmonary surfactant protein A (SP-A) in the developing human fetal lung was performed using a monoclonal antibody, PE10, against human SP-A. At 21 weeks of gestation, a few bronchial cells positive to PE10 were observed to be scattered in the main and segmental bronchi. The number of these cells appears to increase until the 32nd week of gestation, and then decrease thereafter, almost disappearing by 39 weeks. On the other hand, alveolar type II cells and Clara cells positive to PE10 began to appear at 29 weeks, increase in number until around 39 weeks, and remain constant throughout adulthood. A few bronchial glandular cells positive to PE10 were still noticed in the fetal lung. This is the first report of the presence of SP-A-containing cells in the fetal lung. This is the first report of the presence of SP-A-containing cells in the human fetal bronchial epithelium (not Clara cells in the terminal bronchiolus), proving the regularity of the sequential distribution of SP-A-containing cells in the bronchoalveolar system during pulmonary development.

Successful treatment tailored to each splanchnic arterial lesion due to segmental arterial mediolysis (SAM): report of a case.

Segmental arterial mediolysis (SAM) is a rare condition characterized by splanchnic arterial catastrophe caused by mediolysis. We report a 59-year-old man with a ruptured splenic arterial aneurysm who was successfully treated by coil embolization. He underwent additional resection of large gastroepiploic and residual splenic aneurysms. Pathological examination showed mediolysis and tearing, compatible with SAM. Furthermore, he developed acute dissection of the superior mesenteric artery (SMA) one and a half years later, demonstrated by computed tomography. This report demonstrates that SAM is characterized by multiple lesions of the splanchnic arteries at different times, and requires treatment suited to the lesions, including careful long-term observation.

Gastric cancer with metastasis to the gingiva

The present case report describes a gastric cancer which showed unusual metastasis in the oral region. A 56‐year‐old male patient underwent total gastrectomy and splenectomy due to advanced gastric cancer in the upper third of the stomach. Fifteen months later, he presented with anorexia and gingival swelling of durations of approximately 3 and 1 month, respectively. The gastric tumor was histologically a signet ring cell and a poorly differentiated cancer with a moderate degree of vascular invasion. Biopsy specimens from the gingival tumor revealed a signet ring cell cancer. Other metastatic sites were the brain, limb bones and abdominal lymph nodes. A bone scintigram revealed an abnormal uptake in the limb bones, while it did not exhibit any abnormality in the oral region. Correlation between the histology of the gingival tumor with that of the gastric cancer, as well as the absence of a gingival tumor at the time of prior gastrectomy, led to a diagnosis that the gingival tumor was a metastasis from gastric cancer. Gastric cancer metastasizing to the oral region, either the osseus or the oral soft tissue, is very rare. Although it cannot be proved without an autopsy, negative findings in the mandible by bone scanning in the present case suggest that direct gingival metastasis can be considered, rather than mandibular metastasis involving the gingiva. Hematogenous spread could be a mechanism of metastasis for this unusual tumor.

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis

Abstract Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59‐year‐old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low‐grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow‐up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.

MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF A CASE OF MUCOPOLYSACCHARIDOSIS II (HUNTER'S SYNDROME)

An autopsy case of a 19‐year‐old boy who had shown typical gargoyle features, strictly consistent with mucopolysaccharidosis type II (Hunters syndrome) was reported. Histologically, cytoplasmic vacuolar change was found In hepatocytes, sinusoidal epithelium of spleen, follicular cells of thyroid, Sertoli cells of testis, chromophobe cell of pituitary and generalized fibroblast‐like cells including meninges, cardiac valve and periosteum. The vacuoles consisting of membrane‐bound structures with flocculus protein‐like material and occasional electron dense bodies on electron microscopy, were considered to be the site of mucopolysaccharide deposition by histochemical analysis. Deposition of lipid material consistent with so‐called membranous cytoplasmic body was observed in the neurons of central, peripheral and autonomic nervous system. Hepatosplenomegaly could be explained by cytoplasmic deposition, but the cause of cardiomegaly remained further to be studied. Biochemically hepatic mucopolysaccharide was identified as heparan sulfate, while in the kidney dermatan sulfate and heparan sulfate were detected. The correlation between morphology and biochemistry, and between deposition and degeneration was discussed.

Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active degradation process.

Abdominal aortic aneurysm (AAA) is a common disease caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta. Currently no biomarkers have been established to indicate the disease status of AAA. Tenascin‐C (TN‐C) is a matricellular protein that is synthesized under pathological conditions. In the current study, we related TN‐C expression to the clinical course and the histopathology of AAA to investigate whether the pattern of TN‐C expression could indicate the status of AAA. We found that TN‐C and matrix metalloproteinase (MMP)‐9 were highly expressed in human AAA. In individual human AAA TN‐C deposition associated with the tissue destruction, overlapped mainly with the smooth muscle actin‐positive cells, and showed a pattern distinct from macrophages and MMP‐9. In the mouse model of AAA high TN‐C expression was associated with rapid expansion of the AAA diameter. Histological analysis revealed that TN‐C was produced mainly by vascular smooth muscle cells and was deposited in the medial layer of the aorta during tissue inflammation and excessive destructive activities. Our findings suggest that TN‐C may be a useful biomarker for indicating the pathological status of smooth muscle cells and interstitial cells in AAA.

I-CELL DISEASE (MUCOLIPIDOSIS II)

An autopsy case of I‐cell disease was examined by histological, hlstochemlcal, ultrastructural and biochemical methods. Cultured fibroblasts contained numerous PAS‐ and oil‐red O positive granules consistent with lysosomes. The β‐galactosidase activity was specifically low in liver of the patient. The fiboblast‐llke cells Including the cardiac valves, periosteum and stromal cells of the organs were closely similar to those found in mucopolysaccharidoses histochemically as well as ultrastructurally. Lipid‐like materials were observed massively in the myocardium and in the neurons of spinal ganglia, and from these organs excessive amount of ceramlde tri‐hexosides (GTH) was extracted. In a few hepatocytes the dense membrane‐bound bodies suggestive of lipids were found by electron microscopy. Swollen glomerular epithelium contained strongly colloidal‐iron positive material, but the amount of mucopolysaccharides in kidney was not elevated. In this paper, the relationship among the morphology, the material stored and the enzymes was discussed.