Abnormal Nuclear Structures (Micronuclei,Nucleoplasmic Bridges,and Nuclear Buds) in a Pleomorphic Giant Cell Carcinoma of the Stomach

A rare case of pleomorphic giant cell carcinoma of the stomach in a 70-year-old man is reported. Characteristic microscopic findings included a general lack of architectural cohesiveness, aggregates of mononucleated or multinucleated giant cells, extensive areas of coagulative necrosis, and numerous mitoses. Immunohistochemically, tumor cells displayed cytoplasmic immunoreactivity for cytokeratin AE1/AE3 as well as overexpression of p53 and Ki-67. Electron microscopy revealed paranuclear tonofilaments bundles in giant cells confirming their epithelial nature. Furthermore, giant cells contained two or more nuclei with heterogeneous size, nucleoplasmic bridges, nuclear buds, and micronuclei. Similar abnormal nuclear structures have been closely related to breakage-fusion-bridge type of mitotic disturbances in tumor cell lines, and have not been previously reported in a human tumor.     

Anaplastic Thyroid Carcinoma: An Ultrastructural Study of 10 Cases

Anaplastic carcinoma of the thyroid is an aggressive, rapidly fatal neoplasm that is generally believed to arise from the epithelium of the thyroid follicle. When differentiated carcinoma is not present, the diagnosis can be difficult and confusion with a sarcoma is frequently a problem. Ten anaplastic thyroid carcinomas have been examined by light and electron microscopy and compared with two biologically aggressive, solid follicular carcinomas. Ultrastructural study revealed evidence of epithelial differentiation in all the anaplastic carcinomas, confirming their origin from thyroid follicular cells. The study illustrates the value of electron microscopy in establishing the diagnosis of anaplastic carcinoma and in differentiating it from sarcoma.     

Giant Cell Pneumonia: Light Microscopy, Immunohistochemical, and Ultrastructural Study of an Autopsy Case

An autopsy case of measles giant cell pneumonia with intranuclear inclusion bodies is reported. This case of giant cell pneumonia was studied by light microscopy and immunohis-tochemistry using monoclonal and polyclonal antibody to measles and by electron microscopy (EM). Light microscopic examination showed multinucleated epithelial giant cells with intranuclear and intracytoplasmic inclusions. The giant cells contained prominent, sharply marginated, eosinophilic intranuclear inclusions typical of classic measles pneumonia. Presence of measles antigen was confirmed using both monoclonal and polyclonal antibodies by peroxidase antiperoxidase method. Monoclonal antibody stained positively for intracytoplasmic and intranuclear inclusions. Electron microscopic examination of lung tissue showed intranuclear inclusions of filamentous or worm like nucleocapsid materials in multinucleated epithelial giant cells. The results suggest that this is a case of measles giant cell pneumonia and the intranuclear inclusion bodies are measles viral particles.     

Abnormal nuclear structures (micronuclei, nucleoplasmic bridges, and nuclear buds) in a pleomorphic giant cell carcinoma of the stomach

A rare case of pleomorphic giant cell carcinoma of the stomach in a 70-year-old man is reported. Characteristic microscopic findings included a general lack of architectural cohesiveness, aggregates of mononucleated or multinucleated giant cells, extensive areas of coagulative necrosis, and numerous mitoses. Immunohistochemically, tumor cells displayed cytoplasmic immunoreactivity for cytokeratin AE1/AE3 as well as overexpression of p53 and Ki-67. Electron microscopy revealed paranuclear tonofilaments bundles in giant cells confirming their epithelial nature. Furthermore, giant cells contained two or more nuclei with heterogeneous size, nucleoplasmic bridges, nuclear buds, and micronuclei. Similar abnormal nuclear structures have been closely related to breakage-fusion-bridge type of mitotic disturbances in tumor cell lines, and have not been previously reported in a human tumor.     

Basement Membranes in Bronchogenic Squamous Cell Carcinoma: An Immunohistochemical and Ultrastructural Study

Basement membrane (BM) deposition at the interface of tumor cells and stroma was studied in 27 bronchogenic squamous cell carcinomas. Specimens from peripheral and central parts of each tumor were collected. These were frozen, formalin fixed and paraffin embedded or fixed in Karnovsky's fixative, and processed for electron microscopy. With the use of antibodies to type IV collagen and laminin, the BM was visualized by light microscopy with an indirect immunoperox-idase technique. Light microscopic findings were compared to ultrastructural observations. The peripheral parts of the tumors showed continuous BM in a recognizable preexisting alveolar pattern without evidence of invasive growth into the alveolar septa. In contrast, central parts showed highly variable BM deposition ranging from continuous to almost completely absent. Alveolar patterns were not observed in the tumor centers. The stromal compartment of the tumor centers contained many spindle cells with irregular pericellular BM-like material that could be identified ultrastructurally as myofibroblasts. Electron microscopy and immuno-histochemistry yielded virtually identical results. It is concluded that invasive growth in bronchogenic squamous cell carcinomas occurs in central parts of the tumor when the tumor periphery shows expansive growth without invasion of alveolar septa. The situation is different in invasive squamous cell carcinomas originating from other organs because of anatomical differences between the lung and solid organs.     

Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma): Ultrastructural and Immunohistochemical Demonstration of Neurofilaments

In this study we characterized a skin tumor that grew in the temporal region of a 69-year-old woman. On the basis of tumor morphology, a metastasis from a small cell carcinoma of the lung was initially suggested, but X-ray and bronchoscopic studies were negative. The tumor recurred twice within a year, yet no tumors were found elsewhere in the body. Ultrastructurally, cytoplasmic organelles compatible with neuroendocrine storage granules and perinuclear aggregates of intermediate-sized (8-10 nm) filaments were found in many tumor cells. Indirect immunofluorescence microscopy revealed neurofilament-type intermediate filaments in the tumor cells but no keratin-or vimentin-type filaments. Our results further demonstrate neural properties of this tumor type, which is generally considered to have its origin from Merkel cells, the cutaneous neuroendocrine cells.     

Primary Small Cell Neuroendocrine Carcinoma of the Kidney: Morphological, Immunohistochemical, Ultrastructural, and Cytogenetic Study of a Case and Review of the Literature

Poorly differentiated neuroendocrine carcinomas (PDNECs) of the kidney are extremely rare high-grade cancers accounting for only 42 cases reported in the literature. In this paper, we describe the morphological, immunohistochemical, ultrastructural, and for the first time, cytogenetic features of a renal PDNEC. In addition, we have reviewed the literature and compared the published clinicopathological data with our morphological and genetic results. The tumor arose within the kidney parenchyma and showed the typical histological features of a pure small cell PDNEC. Fluorescence in situ hybridization study demonstrated a complex chromosomal assessment indicative of a high degree of chromosome instability with gain of multiple chromosomes, loss of p53, and amplification of myc gene. These results suggest that renal PDNEC has a different genetic background to renal clear cell carcinoma, mainly characterized by the loss of the short arm of chromosome 3. Conversely, genetic alterations seem to resemble those of type 2 papillary renal cell carcinoma. The review of the literature demonstrated that PDNECs are associated with poor prognosis and that parenchymal tumors show some differences from those arising in the pelvis, in that parenchymal tumors are purely neuroendocrine while pelvic tumors are mostly mixed neuroendocrine–exocrine neoplasms.     

Neuroendocrine Carcinoma of the Skin (Merkel Cell Carcinoma): Ultrastructural and Immunohistochemical Demonstration of Neurofilaments

In this study we characterized a skin tumor that grew in the temporal region of a 69-year-old woman. On the basis of tumor morphology, a metastasis from a small cell carcinoma of the lung was initially suggested, but X-ray and bronchoscopic studies were negative. The tumor recurred twice within a year, yet no tumors were found elsewhere in the body. Ultrastructurally, cytoplasmic organelles compatible with neuroendocrine storage granules and perinuclear aggregates of intermediate-sized (8–10 nm) filaments were found in many tumor cells. Indirect immunofluorescence microscopy revealed neurofilament-type intermediate filaments in the tumor cells but no keratin-or vimentin-type filaments. Our results further demonstrate neural properties of this tumor type, which is generally considered to have its origin from Merkel cells, the cutaneous neuroendocrine cells.     

Multinucleated Giant Stromal Tumor of the Omentum: Report of a Case with Immunohistochemical and Ultrastructural Investigation

Multinucleated giant stromal cells (MGSC) have been described in a variety of lesions of various anatomical sites. They are generally believed to be derived from fibroblasts or myofibroblasts. Their size and bizarre appearance may lead to an erroneous interpretation of infiltrating malignant cells, but they are regarded as reactive in nature. MGSC also seem to participate in a neoplastic process and form a part of tumors called giant cell fibroblastomas (GCF). In GCF, multinucleated giant cells are sparsely scattered throughout the tumor, which is composed of loosely arranged spindle cells. Thus far, no tumor composed of MGSC entirely, to the best of the authors' knowledge, has been reported. This study involved an 80-year-old female with an omental tumor, which is believed to represent the first case of tumor of MGSC. The patient developed abdominal pain; a large abdominal tumor measuring 18 × 15 × 5 cm by computerized tomography was found located between the left lobe of the liver, the transverse colon, and the greater curvature of the stomach. Although the tumor was adherent to the above organs and infiltrating the omentum, it was resectable. Grossly, the tumor was highly vascular and the surface was shaggy with no recognizable capsule. The cut surfaces were red to tan with frequent cystic spaces containing bloody material. Microscopically, the tumor cells were large and multinucleated (2-6 nuclei) with prominent nucleoli. The cytoplasm was abundant and stained amphophilic. These tumor cells formed moderately cellular sheets filling the spaces between the varying sized vessels. There was prominent vascularity throughout the tumor. DNA study by image analysis revealed aneuploidy peaks. On immunohistochemis-try, the tumor cells were strongly positive for vimentin, moderately positive for actin along the periphery of the cytoplasm, and negative for cytokeratin, EMA, myoglobin, S-100, CEA, Factor Xllla, HMB-45, and HAM56 and KP-1. Ultrastructurally, the cytoplasm contained rich profiles of RER with scattered lysosomes. The cell borders were slightly irregular with occasional subplasmalemmal densities facing loosely arranged collagenous stroma. The light microscopic, immunohistochemical, and electron microscopic features of tumor cells were remarkably similar to MGSC. The tumor size and gross appearance suggested a malignancy, but it was a diploid tumor and the patient remains disease free 5 years after a complete resection.     

Amphicrine Medullary Carcinoma of the Thyroid with Luminal Differentiation: Report of an Immunohistochemical and Ultrastructural Study

A case of amphicrine medullary carcinoma of the thyroid is presented. The patient was an 18-year-old female with nonhereditary MEN lib, submucosal neuromas in the oral cavity, and a thyroid tumor that metastasized to regional lymph nodes. Histologically the thyroid tumor was composed of polygonal cells arranged in a solid/trabecular pattern admixed with mucus-producing goblet cells and displaying focal cytoplasmic lumen formation. Immunohistochemical stains were positive for calcitonin, carcinoembryonic antigen, and chromogranin. Electron microscopy demonstrated C-cells containing neurosecretory granules as well as intestinal-type microlumina. The presence of goblet cells and intestinal-type microlumina in medullary carcinoma of the thyroid is reminiscent of amphicrine tumors of the gastrointestinal tract and supports the hypothesis that the parafollicular C-cells of the thyroid may be of endodermal derivation.     

Amphicrine Medullary Carcinoma of the Thyroid with Luminal Differentiation: Report of an Immunohistochemical and Ultrastructural Study

A case of amphicrine medullary carcinoma of the thyroid is presented. The patient was an 18-year-old female with nonhereditary MEN lib, submucosal neuromas in the oral cavity, and a thyroid tumor that metastasized to regional lymph nodes. Histologically the thyroid tumor was composed of polygonal cells arranged in a solid/trabecular pattern admixed with mucus-producing goblet cells and displaying focal cytoplasmic lumen formation. Immunohistochemical stains were positive for calcitonin, carcinoembryonic antigen, and chromogranin. Electron microscopy demonstrated C-cells containing neurosecretory granules as well as intestinal-type microlumina. The presence of goblet cells and intestinal-type microlumina in medullary carcinoma of the thyroid is reminiscent of amphicrine tumors of the gastrointestinal tract and supports the hypothesis that the parafollicular C-cells of the thyroid may be of endodermal derivation.     

Glycogen-rich Clear Cell Carcinoma of the Urethra: An Ultrastructural Study

A 49-year-old black woman developed a urethral glycogen-rich clear cell carcinoma. She was treated with anterior pelvic exenteration. The resected lymph nodes, vagina, uterine cervix, endometrium, ovaries, and urinary bladder were free of neoplasm. Histologically the neoplasm consisted of clear cells growing in sheets and occasional papillary structures. In some areas, hobnail cells were present. Ultrastructurally, the cells had apical caps, short microvilli, and complex cell bases, and contained abundant glycogen. These features were identified in one, but not the other of two previously reported cases. Because glycogen-rich clear cell carcinomas of the lower urinary tract do not resemble ultrastructurally mesonephric remnants or carcinomas known to arise from them, these glycogen-rich clear cell carcinomas should not be called “me-sonephromas” as has been the practice.     

Differential Diagnosis between Uterine Carcinosarcoma versus Carcinoma with Sarcomatous Metaplasia: An Immunohistochemical and Ultrastructural Case Study

Uterine carcinosarcomas are biphasic neoplasms with carcinomatous and sarcomatous elements. However, several elements suggest that carcinosarcomas may be more closely related to carcinoma of the endometrium and that they arise from an unique stem cell. Recently, the authors observed an uterine tumor that at histologic examination showed an apparently double population of cells: malignant epithelial element admixed with mesenchymal spindle-shaped cells. The immunohistochemical stainings instead showed cytokeratin positivity and negativity for stromal markers. Electron microscopy showed the neoplastic tissue to be made of a single population of poorly differentiated epithelial cells, thus confirming the immunohistochemical findings and leading to the diagnosis of uterine metaplastic carcinoma.     

Glycogen-rich Clear Cell Carcinoma of the Urethra: An Ultrastructural Study

A 49-year-old black woman developed a urethral glycogen-rich clear cell carcinoma. She was treated with anterior pelvic exenteration. The resected lymph nodes, vagina, uterine cervix, endometrium, ovaries, and urinary bladder were free of neoplasm. Histologically the neoplasm consisted of clear cells growing in sheets and occasional papillary structures. In some areas, hobnail cells were present. Ultrastructurally, the cells had apical caps, short microvilli, and complex cell bases, and contained abundant glycogen. These features were identified in one, but not the other of two previously reported cases. Because glycogen-rich clear cell carcinomas of the lower urinary tract do not resemble ultrastructurally mesonephric remnants or carcinomas known to arise from them, these glycogen-rich clear cell carcinomas should not be called “me-sonephromas” as has been the practice.     

Columnar Cell Carcinoma of the Thyroid: MIB-1 Immunoreactivity as a Prognostic Factor

We report a case of columnar cell carcinoma of the thyroid. A 47-year-old Japanese man had a nonencapsulated thyroid mass that infiltrated the surrounding tissues extensively. Seventeen months after thyroidectomy he died of respiratory failure resulting from tracheal invasion. An autopsy showed distant metastases to the liver, lung, esophagus, and pancreas. Histologically, the thyroid mass consisted of tall columnar atypical cells with marked nuclear stratification. About one-fifth of tumor cells were immunopositive for MIB-1. The MIB-1 positive index of our case was extremely high, compared with that of ordinary papillary carcinoma. This case indicates that biological growth activity in columnar cell carcinoma may be similar to that of undiferentiated carcinoma of the thyroid, since the MIB-1-positive index is close to each other.     

Intriguing Case: Pulmonary Blastoma: An Ultrastructural and Immunohistochemical Study with Special Reference to Nuclear Filament Aggregation

A case is presented of pulmonary blastoma occurring in the right upper lobe of a 25-year-old man without distinct clinical features and laboratory abnormality. Light microscopic analysis revealed that the tumor was composed of branching glands and morulae embedded in a primitive but bland mesenchyme. Immunohistochemically the epithelial cells were im-munoreactive for cytokeratins, S-100 protein, protein gene product 9.5, chromogranin A, calcitonin, and Ki-67 (MIB-1); the mesenchymal cells were immunoreactive for vimentin, actin, cytokeratins, and Ki-67; and all the tumor cells were negative for p53, estrogen receptor protein, and human chorionic gonadotropin ß. Characteristically, many epithelial cells contained optically clear nuclei which were immunoreactive for biotin (M743). Electron microscopic analysis revealed that the optically clearing change was due to replacement of the central area of the nuclei by a mass of parallel-arranged 7- to 10-nm filaments, and biotin-immunoreactive products were mainly localized in the nuclear matrix. Additionally, spherical bodies were identified in the cytoplasm of the nuclear filament-aggregated cells, suggestive of an intimate pathogenetic association of the two morphological abnormalities. The similarity of the aggregated nuclear filaments to those observed in gestational endometrium and ovarian endometrioid carcinoma implies that a similar mechanism plays a role in the pathogenesis of these abnormalities.     

Myxoid Leiomyosarcoma of the Kidney Accompanying Ipsilateral Ureteral Transitional Cell Carcinoma: A Case Report with Cytological, Immunohistochemical and Ultrastructural Study

The authors report a case of myxoid leiomyosarcoma of the kidney accompanying ipsilateral ureteral transitional cell carcinoma. A 74-year-old male patient complained of turbid urine and macroscopic hematuria. He also complained of left back pain, appetite loss and weight loss. Computed tomography revealed a large mass in the left retroperitoneum. Urine cytology disclosed two types of malignant cells, atypical spindle-shaped cells and transitional cell carcinoma. Left total nephro-ureterectomy was performed. The left kidney was occupied by a 6X4X4 cm, multinodular and mucinous tumor. A transitional cell carcinoma of the left ureter was also observed. The renal tumor was composed of atypical spindle-shaped cells in the mucinous stroma, which showed positive immunoreactivity for anti-muscle-specific actin and anti-desmin antibodies. The ultrastructural examination revealed intracytoplasmic microfilaments with dense bodies, pinocytotic vesicles and junctional structure. These findings were suggestive of the myogenic feature of the case. Urine cytology revealed a number of sarcoma cells in this case since the sarcoma cells markedly invaded the renal pelvis and were apt to separate individually in myxoid stroma. Simultaneous and ipsilateral double malignancies of the renal sarcoma and ureteral transitional cell carcinoma have never been reported in the literature. Acta Pathol Jpn 41: 694–700, 1991.     

An Immunohistochemical and Ultrastructural Study of Case of Small-cell Neuroendocrine Carcinoma in the Ampullary Region of the Duodenum

One case of small-cell neuroendocrine carcinoma in the ampullary region of the duodenum is reported. The histological appearance of the tumor was identical to pulmonary small-cell carcinoma. Neuroendocrine differentiation was demonstrated immunohistochemically by positive immunoreaction for neuron specific enolase, Leu 7 and chromogranin, and ultrastructurally by the presence of scanty dense core neurosecretory type granules. Small-cell neuroendocrine carcinoma in the ampulla of Vater is extremely rare. To our knowledge, this is the sixth reported case.     

Primary Small Cell Neuroendocrine Carcinoma of the Urinary Bladder: A Clinicopathologic,Immunohistochemical, and Ultrastructural Evaluation

Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare but aggressive neoplasm that usually exhibits neuroendocrine differentiation. Here, the authors report a case of SCNEC in an 80-year-old man. The patient had gross hematuria and nodular mass involving the wall of the urinary bladder. Total cystectomy was done. The tumor consisted of small, uniform, round, and spindled-shaped cells with chromatin dark nuclei and numerous mitotic figures. The cells were reactive for chromogranin, neuron-specific enolase (diffuse), and keratin (focal). Ultrastructural studies revealed neurosecretory granules and intermediate filaments. The diagnosis of SCNEC with focal high-grade urothelial component was established. No metastasis was found at the time of diagnosis and the patient refused further chemotherapy or radiotherapy. The histogenesis, differential diagnosis, and prognosis of SCNEC of the urinary bladder were discussed.     

Immunohistochemical Features of Giant Cell Carcinoma of the Lung: Patterns of Expression of Cytokeratins, Vimentin, and the Mucinous Glycoprotein Recognized by Monoclonal Antibody A-80

Giant cell carcinoma of the lung (GCCL) is an uncommon and extremely aggressive variant of lung cancer. Characteristic microscopic findings include marked pleomorphism, aggregates of mononucleated or multinucleated giant cells (or both), a general lack of architectural cohesiveness, extensive necrosis, and endocytosis by the giant cells. Although the epithelial character of GCCL has been confirmed by a number of studies, controversy persists as to whether it represents a variant of poorly differentiated adenocarcinoma or of squamous carcinoma. Histochemical studies for mucosubstances have yielded variable and conflicting results. This report describes conventionally fixed and processed samples from 10 cases of GCCL studied with a panel of monoclonal antibodies (Mabs) recognizing different cytokeratin polypeptides (AE1, AE3, AE1/AE3 cocktail, and CAM 5.2), vimentin, and Mab A-80, the last of which binds to a mucinous glycoprotein associated with exocrine differentiation. All 10 cases of GCCL reacted with all cytokeratin Mabs; the extent and intensity of the reaction varied notably. All cases stained strongly and diffusely with Mab AE1 and AE1/AE3, the reaction was less extensive and weaker with CAM 5.2. Significantly, 2 cases reacted focally with Mab AE3. Nine cases reacted extensively and intensely with the vimentin Mab, often showing prominent paranuclear globular profiles. All cases reacted with Mab A-80; the reaction was often strong, but the extent was variable. Findings indicate that all GCCL are indeed cytokeratin positive but that most express polypeptides toward the low-molecular weight end of the spectrum; a small subset also expresses heavier polypeptides. This profile suggests that all GCCL display cytokeratins characteristic of adenocarcinoma but that a subset also shows polypeptides typical of squamous carcinomas; significantly, all GCCL retained their exocrine phenotype as defined by their positivity with Mab A-80. Moreover, the consistent if not invariable finding of vimentin positivity adds to an immunohistochemical profile that is distinct from that of the vast majority of lung cancers.