Simultaneous production of amylase and adrenocorticotropin by lung cancer--with special reference to electron microscopic and immunohistochemical studies

The tumor tissue from a lung cancer patient who showed elevated serum amylase and adrenocorticotropin was investigated ultrastructurally and immunohistochemically. On microscopic examination, the tumor was diagnosed as small-cell carcinoma. Electron microscopy revealed that some of the tumor cells possessed small endocrine-like dense cored granules. The tumor cells also contained large zymogen-like granules within the cytoplasm, which possessed microvilli and formed the lumen, indicating their adenocarcinomatous differentiation. An electrophoretic analysis of the serum amylase showed that the major amylase elevated was of the salivary type. Immunohistochemical staining by the antihuman salivary amylase antibody disclosed that various portions of the tumor actually contained the salivary amylase. The evidence suggests that the small-cell carcinoma cells showed "confused differentiation", thereby expressing amylase and ACTH simultaneously.     

Pleomorphic adenoma of the salivary gland. With special reference to histochemical and electron microscopic studies and biochemical analysis of glycosaminoglycans in vivo and in vitro.

Pleomorphic adenoma of the salivary gland is classified into two types based on the morphology of the cells and biochemical analysis of glycosaminoglycans. Type 1: the tumors consisted mainly of spindle cells, producing a large amount of mucinous material, and contained not only chondroitin 4- and 6-sulfate and hyaluronic acid but also heparan sulfate. When the tumors of this type were dissociated and cultivated, spindle cells proliferated vigorously as mulitlayer and secreted mucinous substance into the intercellular space. The cells looked like non-epithelial cells in a conventional culture bottle, but showed an epithelial-like arrangement when they were cultivated in sponge matrix or inoculated subcutaneously into mice. Fine fibres stained with orceine or resorcin-fuchsin were observed in the intercellular material both in resected tissue and in culture. Type 2: the tumors consisted mainly of ductal cells, having no mucinous area, and contained little heparan sulfate. When the tumors were cultivated, the growth of epithelial-like polygonal cells was observed in monotonous pattern, producing scanty intercellular substance, and proliferating, as monolayer, much less rapidly than the cells of Type 1.     

Light and electron microscopic studies of perineural invasion by esophageal carcinoma

Light and electron microscopic findings on perineural invasion by human esophageal squamous cell carcinoma are reported. Perineural invasion was observed histologically in 30 of a total of 129 cases (23%) of esophageal squamous cell carcinoma and in 11 of the 24 cases (46%) in which tumors infiltrated other organs by passing through the esophageal adventitial layer. Electron microscopic observation showed that the perineurium of peripheral nerves was completely surrounded by carcinoma cells and that marked degeneration and loss of perineural cells occurred. Irregularly thickened basal laminae were detected in the perineurium. For nerves incompletely surrounded by carcinoma tissue, the free portion of the perineurium revealed degenerative findings similar to those for completely surrounded nerves. Cytoplasmic projections of the leading margin of the invading cancer tissue were located in the degenerated perineurium, contained many lysosomes, and were not always surrounded by basal laminae. These observations suggest that invading carcinoma tissue actively contributes to the degeneration of the perineural sheath and that the special pattern of carcinoma tissue surrounding the peripheral nerves results from infiltration along the degenerated sheath of the perineurium.     

Malignant struma ovarii. Light and electron microscopic study

Malignant struma ovarii is a very rare tumor, consisting of a struma ovarii with malignant change. Only 17 examples with metastases have previously been reported. We present a case which involved both ovaries and produced multiple metastases. Microscopy and ultrastructure were identical to a mixed papillary and follicular carcinoma of the thyroid gland. Characteristic ultrastructural features of malignant struma ovarii are: microvilli on the surface and in the cytoplasmatic vacuoles; oncocytic transformation of cytoplasm of some cells; and presence of electron dense, granular and crystalline material (colloid) in the follicles and vacuoles. The patient's thyroid was normal. We conclude that malignant struma ovarii can only be diagnosed wheb a carcinoma arising in the thyroid gland can be excluded. Ultrastructure examination may provide useful diagnostic features separating malignant struma ovarii from strumal carcinoid and serous adenocarcinoma.     

Health effects of cadmium with special reference to studies in Japan.

This paper gives an overview of the health effects of cadmium with special emphasis on the natural history of cadmium poisoning. The following questions are discussed: (1) Do the renal changes caused by cadmium result in both glomerular and tubular dysfunction? (2) What is the fate of these renal changes? (3) What is the relationship between renal changes and osteomalacia? (4) Is there a dose-response relationship between cadmium exposure and renal dysfunction? (5) What is the solution to the enigma of cadmium and respiratory cancer? Although innumerable papers have been published, the above questions remain unanswered. The natural history of cadmium poisoning is ironically more complicated than that of communicable diseases in man despite the fact that the element is static and not propagated in living organisms.     

Aspiration cytology of neuroblastoma. Light and electron microscopic correlations

Fine-needle aspiration biopsy (FNAB) smears from 16 cases of neuroblastoma are reviewed, and various cytomorphologic features helpful in diagnosing this tumor are described. Cytoplasmic processes were present in ten cases, and pseudorosettes in three cases. Electron microscopic study of FNAB samples revealed that all diagnostically important features, such as cell processes, neurosecretory granules, and synaptic cell junctions, could be recognized. These findings indicate that FNAB studied by light and electron microscopy is an effective method for diagnosing neuroblastoma.     

Light and electron microscopic studies on a transplantable thyrotrophic pituitary tumor in the mouse

A transplantable pituitary tumor induced in a male C57Bl mouse by radiothyroidectomy has been studied by light and electron microscopy. The primary tumor was highly differentiated and composed of hypersecretory cells which showed the morphological characteristics of the thyroidectomy cell. The tumor was followed through four transfers in radiothyroidectomized hosts. Autonomous tumors growing in normal hosts appeared during the fifth transfer generation. The first dependent tumor grafts showed highly differentiated cells of the same appearance as the primary tumor cells. Through the following transfers there was a progressive dedifferentiation of the tumor cells although the majority of them could, in the electron microscope, be identified as thyrotrophic tumor cells with morphological signs of secretory function. In the autonomous tumors most of the cells were dedifferentiated and only a few cells showed signs of secretory function. The results of the morphological study support earlier observations on the hormone activity of transplantable thyrotrophic tumors. These have shown that primary and dependent tumors are highly functional, but that autonomous tumors display a progressive decrease in hormone production. The findings also confirm earlier morphological observations that autonomous tumors are dedifferentiated, but both the light and electron microscopic observations in this study suggest that there is a progressive dedifferentiation of tumor cells in hormonedependent tumors as well.     

Aspiration cytology of Ewing's sarcoma. Light and electron microscopic correlations

Fine-needle aspiration biopsy specimens from 15 histologically proven cases of Ewing's sarcoma of the bone were studied by both light and electron microscopy. Large glycogen deposits in the Ewing's sarcoma cells could be easily recognized in smears stained routinely with Diff-Quik (American Scientific Product, McGraw Park, IL). These deposits appeared as punched-out clear spaces in the cytoplasm. Ultrastructurally the tumor cells could be divided into chief cells and dark cells. The chief cells were further categorized based on their nuclear morphologic features into cleaved, noncleaved, and intermediate cells. The dominant cell was noncleaved in eight, cleaved in three, and intermediate in four cases. All five tumors with abundant glycogen were composed predominantly of noncleaved cells. The tumor cells in aspiration material appeared to be irregular in shape, and some had cytoplasmic processes. In one tumor these processes were quite prominent; this caused some difficulty in differentiation from neuroblastoma.     

Hypothesis for the histogenesis of atypical epithelial proliferation in the stomach

Atypical epithelial proliferation has been described in various ways, such as ATP, and IIa-subtype, an adenoma, and as dysplasia in the stomach. Although the gross findings are variable, showing a protruded and/or concave appearance, these lesions have an intimate relationship with the intestinal metaplasia. Atypical epithelial proliferation lesions develop in 2 fashions. The first type, of proliferation is a superficial type with the capability of transition to the deep non-atypical glands, and may arise in association with a superficial type of intestinal metaplasia. The second type of proliferation may arise from an area affected by complete intestinal metaplasia, in the mitotic region in the bottom of the gland. The majority of the protruded types may arise from the first lesion described, and the majority of the concave types from the second.     

Diffuse heterotopic multiple cysts of the stomach with special reference to the histogenesis and relationship with gastric cancer

Ten patients with diffuse multiple glands or cysts in the submucosal layer of the stomach have been extensively studied. The structure of the cyst wall showed two patterns, consisting of monolayer cuboidal or cylindrical cells and pseudoantral or parietal mucosa. All of the multiple cysts were in the submucosal layer under the gastric mucosa with intestinal metaplasia. In these mucosal layers, erosion and ulcer were frequently observed. Four patients had multiple gastric cancers, and the cancers were surrounded by the metaplastic gastric mucosa. We speculated this disorder to be a peculiar regenerative change after gastritis, especially erosion. That repeated erosion and regeneration leads to carcinoma in the stomach with diffuse, heterotopic multiple cysts.