Adrenocortical carcinoma in infancy. Report of a case with immunohistochemical and ultrastructural studies

A case of adrenocortical carcinoma associated with congenital heart defect in a 6-month-old Japanese girl is reported. A fist-sized tumor was incidentally noted in the right hypochondrium upon admission for cardiac surgery. No clinical endocrinopathy was evident in this case. The resected tumor was encapsulated with smooth surface and no invasion to adjacent tissues or organs was observed. Histologically, the tumor was composed of small cells with granular or clear cytoplasm, and occasional giant cells with single or multiple nuclei. By electron microscopy, the tumor cells showed various nuclear contours with distinct nucleoli and had a moderate amount of cytoplasm containing abundant rough endoplasmic reticulum and mitochondria with variable-sized electron-dense granules. Intercellular desmosome-like junctions were observed in some tumor cells. Immunohistochemically, the tumor cells contained granules positive for estriol, progesterone and cortisol. These morphological findings including electron microscopic features suggested that the tumor cells had a malignant character.     

结肠嗜酸细胞癌2例临床病理分析

目的 探讨结肠嗜酸细胞癌的病理组织学特点、诊断及鉴别诊断。方法 对2例结肠嗜酸细胞癌手术切除标本进行光镜、免疫组化染色及电镜观察。结果 结肠嗜酸细胞癌组织学特点为细胞圆形、多边形,胞质丰富,胞质内见弥漫分布的强嗜酸性颗粒,细胞核中度异型性,核仁明显;癌细胞呈巢状排列,伴有腺管及乳头形成。免疫表型：癌细胞CK19、EMA阳性表达,不表达SMA、S-100蛋白及CgA。PAS染色阴性。电镜观察细胞质充满大量线粒体,缺乏内分泌及外分泌颗粒。结论 嗜酸细胞癌是不同于低分化腺癌及神经内分泌癌的一种特殊类型细胞癌。     

LIGHT AND ELECTRON MICROSCOPIC STUDY OF NONFUNCTIONING PARATHYROID CARCINOMA

A case of nonfunctioning parathyroid carcinoma in a 69-year-old female has been studied by light and electron microscopy. The tumor, located on the left side of the anterior neck, was well encapsulated by connective tissue but showed invasion to the capsule and to the thyroid. The tumor cells exhibited a trabecular arrangement surrounded by capillary networks but focally showed several ductal structures. They were polygonal in shape, had a large nucleus showing frequent mitosis and poor cytoplasm containing glycogen. Some tumor cells had clear and abundant cytoplasm, and resembled water-clear cells of the parathyroid. Immunohistochemically, no thyroglobulin was demonstrated in the tumor tissue. Electronmicroscopically, the tumor cells with high N/C ratio contained poorly developed cell organelles and abundant glycogen particles. They were poor in secretory granules and had no conglomeration of lipid. Desmosomes and tonoflbrils were observed. The ratio of the reported number of nonfunctioning parathyroid carcinoma to that of functioning one in Japan was compared with that in western countries. No difference of the ratio was found between these two, when identical criteria were employed.     

Pseudopapillary solid cystic tumor arising from an extrapancreatic site

A case of pseudopapillary solid cystic tumor arising in the omentum of a 46-year-old woman is presented. A well-defined, encapsulated tumor measuring 5.2 x 4.0 x 4.0 cm was histologically characterized by a combination of solid and pseudopapillary growth patterns of tumor cells with abundant pale-to-eosinophilic cytoplasm. No pancreatic tissue was observed within or adjacent to the tumor. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and alpha1-antichymotrypsin. Ultrastructurally, the tumor cells contained electron dense granules of variable sizes, most likely representing lysosomes. Flow cytometry showed a diploid DNA content with a high S-phase fraction. The patient was well without recurrence 3 months after diagnosis. It is important to include pseudopapillary solid cystic tumor in the differential diagnosis of omental tumors.     

Hepatocellular Carcinoma Containing Endocrine CelIs: An Autopsy Report of Triplecancer Involving the Liver, Kidney and Thyroid

An autopsy case of triplecancer (hepatocellular carcinoma of the liver, renal cell carcinoma of the kidney, and papillary carcinoma of the thyroid) was reported. Histological features of primary hepatic tumor suggested undiffer-entiated hepatocellular carcinoma (Edmondson Steiner's Grade IV). However, certain tumor cells showed distinctive argyrophilic reactions and electron microscopy revealed small round granules resembling electron dense endocrine secretory granules in their cytoplasm. Immuno-histochemistry demonstrated that tumor cells showed a positive reaction for AFP while some others were positive for chromogranin A. lmmunohistochemical demonstration of AFP production by tumor cells indicated their he-patocyte origin. No endocrine syndrome had been present and no alternative primary source of the endocrine tumor was detected. Tumors of the kidney and thyroid were considered to be incidentally combined. Acta Pathol Jpn 42: 904–910, 1992.     

Neuroendocrine carcinomas of the skin: light microscopic, ultrastructural, and immunohistochemical analysis

Three primary skin carcinomas were analyzed by light microscopy, immunohistochemistry, and electron microscopy. In all cases, local recurrences, regional lymph node metastases, distant metastases, or all three developed. One patient had elevated serum calcitonin levels that did not decrease after thyroidectomy but did return to normal after removal of the skin tumor recurrences, its metastases, or both. The tumor cells were arranged in solid clusters; a trabecular arrangement was occasionally seen. In 2 cases the cells were of intermediate size and showed vesicular central nuclei and pale, moderately abundant cytoplasm. In the remaining case the cells were distinctly smaller and either round or fusiform. Mitoses were more abundant in the latter case than in the former two. By immunohistochemistry, calcitonin- and somatostatin-containing cells were demonstrated in all cases and ACTH in one. By electron microscopy, the cases consisting of intermediate-size cells displayed moderately abundant neurosecretory-type granules irregularly dispersed throughout the cytoplasm. The case consisting of smaller cells displayed fewer and smaller granules that tended to concentrate in slender cytoplasmic processes. We conclude that these tumors constitute parts of the broadening spectrum of neuroendocrine skin carcinomas that may derive from Merkel cells.     

Hepatocellular carcinoma containing endocrine cells. An autopsy report of triplecancer involving the liver, kidney and thyroid.

An autopsy case of triplecancer (hepatocellular carcinoma of the liver, renal cell carcinoma of the kidney, and papillary carcinoma of the thyroid) was reported. Histological features of primary hepatic tumor suggested undifferentiated hepatocellular carcinoma (Edmondson-Steiner's Grade IV). However, certain tumor cells showed distinctive argyrophilic reactions and electron microscopy revealed small round granules resembling electron dense endocrine secretory granules in their cytoplasm. Immunohistochemistry demonstrated that tumor cells showed a positive reaction for AFP while some others were positive for chromogranin-A. Immunohistochemical demonstration of AFP production by tumor cells indicated their hepatocyte origin. No endocrine syndrome had been present and no alternative primary source of the endocrine tumor was detected. Tumors of the kidney and thyroid were considered to be incidentally combined.     

ULTRASTRUCTURAL STUDIES ON A CAROTID BODY TUMOR

Light and electron microscopic studies were made on a large carotid tumor. Light microscopy revealed adenomatous formation with dark granules giving a positive Grimelius silver reaction in the lumen and cytoplasm of chief cells. Electron microscopy showed that the tumor consisted mainly of clear cells and a few dark cells. Electron dense granules were observed both in the cytoplasm of the tumor cells and in the lumen. Microfilaments were prominent in the cytoplasm of both types of tumor cells.     

Atypical thymoma (WHO B3) with neuroendocrine differentiation: report of a case

We report a case of type-B3 thymoma manifesting neuroendocrine differentiation. The patient was a 42-year-old woman who complained of shoulder pain but had no symptoms of myasthenia gravis or anemia. The tumor was located in the anterior mediastinum and had directly invaded the pericardium and left lung. Histological examination revealed that the tumor was lobulated by bands of fibrous tissue, perivascular spaces were scattered throughout the tumor, and there were a few intraepithelial lymphocytes. The vast majority of lymphocytes in the perivascular spaces and in the lobulated tumor were immunohistochemically positive for TdT, MIC2, and CD1a. The majority of tumor cells were polygonal and medium or large in size. The tumor cells were weakly positive for synaptophysin, chromogranin A, CD56, and NSE. Small nests of small, relatively uniform polygonal cells were observed facing the fibrous bands. These cells resembled the cells of carcinoid tumors and were strongly positive for NSE, synaptophysin, chromogranin A, and CD56. Ultrastructurally, sparse dense-core granules were observed in the cytoplasm of a few tumor cells. This is a unique case of thymoma with neuroendocrine differentiation, and to the best of our knowledge this is the first such case ever reported.     

Neuroendocrine Carcinomas of the Skin: Light Microscopic,Ultrastructural, and Immunohistochemical Analysis

Three primary skin carcinomas were analyzed by light microscopy, immunohistochemistry, and electron microscopy. In all cases, local recurrences, regional lymph node metastases, distant metastases, or all three developed. One patient had elevated serum calcitonin levels that did not decrease after thyroidectomy but did return to normal after removal of the skin tumor recurrences, its metastases, or both.

The tumor cells were arranged in solid clusters; a trabecular arrangement was occasionally seen. In 2 cases the cells were of intermediate size and showed vesicular central nuclei and pale, moderately abundant cytoplasm. In the remaining case the cells were distinctly smaller and either round or fusiform. Mitoses were more abundant in the latter case than in the former two.

By immunohistochemistry, calcitonin- and somatostatin-containing cells were demonstrated in all cases and ACTH in one. By electron microscopy, the cases consisting of intermediate-size cells displayed moderately abundant neurosecretory-type granules irregularly dispersed throughout the cytoplasm. The case consisting of smaller cells displayed fewer and smaller granules that tended to concentrate in slender cytoplasmic processes.

We conclude that these tumors constitute parts of the broadening spectrum of neuroendocrine skin carcinomas that may derive from Merkel cells.     

Paraganglioma of the Cauda Equina

A case of paraganglioma of the cauda equina is reported. The patient was a 55 year old Japanese woman who complained of lower back pain and gradual weakening of the left lower extremity, she was diagnosed as having a spinal cord tumor, and the tumor was removed surgically. Histologically, the tumor was encapsulated, and consisted of solid nests of large, polyhedral epithelioid cells with abundant eosinophilic cytoplasm. The nests were separated from each other by a thin fibrovascular stroma. Grimelius staining revealed neurosecretory granules in the cytoplasm of the tumor cells. This was further confirmed by electron microscopic observation. The tumor cells were immunohistochemically positive for neuron-specific enolase (NSE), but negative for glial fibrillary acidic protein (GFAP). On the basis of the histologic, immunohisto-chemical and electron microscopic features of the tumor cells, the tumor was diagnosed as paraganglioma. The cauda equina is a rare location for this type of tumor, and only a limited number of cases have been reported.     

Paraganglioma of the cauda equina. A case report and review of the literature

A case of paraganglioma of the cauda equina is reported. The patient was a 55-year-old Japanese woman who complained of lower back pain and gradual weakening of the left lower extremity, she was diagnosed as having a spinal cord tumor, and the tumor was removed surgically. Histologically, the tumor was encapsulated, and consisted of solid nests of large, polyhedral epithelioid cells with abundant eosinophilic cytoplasm. The nests were separated from each other by a thin fibrovascular stroma. Grimelius staining revealed neurosecretory granules in the cytoplasm of the tumor cells. This was further confirmed by electron microscopic observation. The tumor cells were immunohistochemically positive for neuron-specific enolase (NSE), but negative for glial fibrillary acidic protein (GFAP). On the basis of the histologic, immunohistochemical and electron microscopic features of the tumor cells, the tumor was diagnosed as paraganglioma. The cauda equina is a rare location for this type of tumor, and only a limited number of cases have been reported.     

Estrogen-producing adrenocortical carcinoma. A light and electron microscopic study

A case of adrenocortical carcinoma with feminization seen in a man aged 35, is reported. The levels of estron (E1) and estradiol (E2) in the venous blood draining the tumor were high, and it was confirmed by in vitro assay of tumor cells taken from the primary tumor of the left adrenal gland that the tumor produced estrone. The light microscopic examination demonstrated that the primary tumor was composed of mixture of large cells with pleomorphic nuclei and vacuolated cytoplasm and uniform cells with ovoid nuclei and eosinophilic cytoplasm. The electron microscopic examination on the latter cells revealed numerous large and irregularly shaped mitochondria with mostly tubular or lamellar and occasionally vesicular cristae and electron-dense matrix, well-developed smooth-surfaced endoplasmic reticulum in the cytoplasm. However, lipid droplets and lysosomes or lipofuscin granules were scanty. From these findings, it is suggested that cells of the present tumor have characteristics of those in the zona reticularis of the adrenal cortex as well as in the fetal cortex, and the functional property of this tumor is well correlated with its morphological features.     

Indeterminate cell tumor of the spleen

Indeterminate cell tumor is an extremely rare neoplasm that mainly occurs in the skin. We report a case of indeterminate cell tumor arising from the spleen, a previously unreported site for indeterminate cell tumor. Histologically, the tumor showed nests, nodules, and sheets of large polygonal cells with mostly oval nuclei; open chromatin; variable nucleoli; and abundant, eosinophilic cytoplasm. Some cells possessed irregularly convoluted nuclei with nuclear grooves and granular cytoplasm, suggestive of Langerhans cells. Immunohistochemically, the tumor cells were diffusely positive for S-100 and CD1a and negative for Langerin. No Birbeck granules were found by electron microscopy. Clinical and radiologic examination showed no other organomegaly or lymphadenopathy. A diagnosis of primary indeterminate cell tumor of the spleen was rendered. To the best of our knowledge, this is the first indeterminate cell tumor reported in the spleen. Biologic insights into dendritic cells in the spleen and the pertinent literature on these entities are reviewed.     

ULTRASTRUCTURAL STUDY OF GRANULAR CELL AMELOBLASTOMA

A granular cell ameloblastoma occurring in the anterior mandible of a 49-year-old woman has been studied both histologically and ultrastructurally. Histologically the tumor in this case showed a mixed type of follicular, granular cell, and acanthomatous type of ameloblastoma. Many granular cells seemed to gather around the periphery of each tumor island. Electron-microscopically the cytoplasmic granules were measured as approximately 0.6 μ in diameter, and were surrounded by limiting membrane. Most of these granules revealed high electron density and their contents showed various patterns — osmiophilic homogeneous, fingerprint, and small particles — and were identified as lysosomes. However, no enamel matrix precursor was identified in either lysosome or cytoplasm. All the granular cells showed regular nuclei and no degeneration. Though lysosomes might play a role of autophagy and of remodeling the cytoplasm, its presence seems to have an active function in tumor cells, as opposed to the aging or degenerating function.     

Alveolar soft part sarcoma of the uterine cervix

A rare case of an alveolar soft part sarcoma of the uterine cervix in an 8 year old girl is presented. The patient was admitted because of genital bleeding lasting for 7 months. A polypoid tumor, 2times1.5 cm in diameter, was found in her external uterine os and was surgically resected. Microscopically, the tumor consisted of a uniform sheet of tumor cells in the cytoplasm which contained granules and which were stained with periodic acid-Schiff, both before and after the diastase digestion. Alveolar arrangement of the tumor cells was manifested with reticulin silver impregnation. Dense, membrane bound granules were evident at an ultrastructural level in the cytoplasm of the tumor cells. An immunohistochemical examination demonstrated a positive reaction for anti-desmin, anti-myoglobin, anti-HHF35 and anti-neuron specific enolase in the cytoplasm.     

Retroperitoneal paraganglioma with multiple pulmonary metastases detected six years after complete resection of the primary tumor

Multiple pulmonary metastases from a retroperitoneal non-functional paraganglioma developed in a 69-year-old woman, who had been operated on for complete resection of a primary tumor about 6 years previously. An open-lung biopsy specimen revealed tumor cells possessing round or oval vesicular nuclei, numerous nucleoli and abundant, granular eosinophilic cytoplasm. Tumor cells showed small nests surrounded by distinct fibrovascular stroma. Upon electron microscopic examination, tumor cells were found to consist of chief cells that contained many mitochondria, a small number of dense-core granules and synapse-like structures. This case was worth reporting in order to emphasize the value of long-term follow-up, even after successful resection, and the usefulness of electron microscopic examination. This study was presented at the 25th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Matsumoto, September 28–30, 1993.     

Mixed Medullary-Follicular Carcinoma of the Thyroid Immunohistochemical and Electron Microscopic Studies

A case of mixed medullary follicular carcinoma of the thyroid is reported. Grossly, the tumor was a solid, grayish white, well circumscribed mass without lymph node metastasis. Microscopically, the tumor showed both medullary and follicular areas. The follicular areas occupied discrete portions of the tumor, and were considered to be neoplastic. Tumor cells in the medullary area were polyhedral or spindle-shaped. There was no amyloid deposition within the tumor. Immunohistochemically, tumor cells in the medullary area were positive for calcitonin and negative for thyroglobulin. Some cells lining the follicles were positive for thyroglobulin. By electron microscopy, two types of tumor cell were observed. One type contained numerous cytoplasmic secretory granules, whereas the other type had few granules and showed a prominent rough endoplasmic reticulum. These findings suggested that this mixed medullary follicular carcinoma of the thyroid presented neoplastic changes within a common cell lineage.     

Mixed medullary-follicular carcinoma of the thyroid. Immunohistochemical and electron microscopic studies

A case of mixed medullary-follicular carcinoma of the thyroid is reported. Grossly, the tumor was a solid, grayish-white, well circumscribed mass without lymph node metastasis. Microscopically, the tumor showed both medullary and follicular areas. The follicular areas occupied discrete portions of the tumor, and were considered to be neoplastic. Tumor cells in the medullary area were polyhedral or spindle-shaped. There was no amyloid deposition within the tumor. Immunohistochemically, tumor cells in the medullary area were positive for calcitonin and negative for thyroglobulin. Some cells lining the follicles were positive for thyroglobulin. By electron microscopy, two types of tumor cell were observed. One type contained numerous cytoplasmic secretory granules, whereas the other type had few granules and showed a prominent rough endoplasmic reticulum. These findings suggested that this mixed medullary-follicular carcinoma of the thyroid presented neoplastic changes within a common cell lineage.     

Pancreatic endocrine tumor with partial acinar cell differentiation

We examined a 70-year-old woman in whom a pancreatic endocrine tumor with partial acinar cell differentiation had been diagnosed. She had neither endocrine nor exocrine symptoms. The tumor was located in the pancreatic tail and measured 12.5 x 9.5 x 8 cm. It had a capsule, was composed of multiple adhesion nodules, and was elastically soft, medullary, and yellowish white. The neoplastic cells had large, irregular, oval nuclei; prominent eosinophilic nucleoli; and abundant eosinophilic cytoplasm with many fine granules. The cells had proliferated in islet-like solid medullary, trabecular, acinar, and papillary patterns. Most neoplastic cells were strongly positive for synaptophysin. 10 to 25% of the neoplastic cells were positive for alpha1-antitrypsin. Neuroendocrine and zymogen granules were simultaneously observed in the cytoplasm of the same neoplastic cells at the ultrastructural level. The tumor may be considered an amphicrine tumor.