Hyalinizing trabecular adenoma of the thyroid. A report of three cases with immunohistochemical and ultrastructural studies

We have studied three examples of benign thyroid tumours which conform to the lesion recently described as hyalinizing trabecular adenoma. The prominent feature of this trabecular epithelial lesion is the extracellular deposition of an eosinophilic material that does not show the features of amyloid; the epithelial cells may be elongated, sometimes radially arranged around the eosinophilic material. All three tumours showed positive immunocytochemical staining for thyroglobulin, keratin, chromogranin and neuron-specific enolase. One tumour showed isolated cells with immunoreactivity for somatostatin, argyrophil cytoplasmic granularity with the Grimelius technique, and ultrastructurally demonstrable cytoplasmic electron-dense endocrine granules. The hyaline extracellular material in all three tumours showed strong immunoreactivity for both type IV collagen and laminin. Previous radiation may be important in the causation of this tumour, and it shows a frequent association with severe thyroiditis. We conclude that the main histological feature of this lesion, the hyaline material, is due to the overproduction of a basement membrane-like material by the neoplastic follicular cells. The presence in one tumour of evidence of endocrine differentiation may reflect the potential for follicular cells to show biphasic differentiation, a feature which may be more frequent than has been previously recognized. Several of the other features of this tumour--for example the frequent intranuclear cytoplasmic inclusions--may lead to diagnostic problems, and the entity deserves wider recognition.     

Medullary carcinoma of the thyroid: a cytological, immunocytochemical, and ultrastructural study.

The cytomorphological features of 38 cases of medullary carcinoma of the thyroid on FNAC were studied. These cases were retrieved from the files of the cytopathology laboratory. In addition, staining for calcitonin (19 cases), thyroglobulin (5 cases), neurone specific enolase (7 cases), and carcinoembryonic antigen (8 cases) was done. Electron microscopy was done in two cases. On morphology, the presence of amyloid together with cytoplasmic granules was found to be diagnostic. The plasmacytoid cell type and the mixed cell populations were most commonly observed. Pseudononuclear inclusions were seen in 58% of cases. Calcitonin was present in 74% of cases. NSE was noncontributory, whereas CEA was positive in one of the calcitonin negative cases.     

Low-grade renal collecting duct carcinoma. A case report with histochemical, immunohistochemical, and ultrastructural study

We report a rare tumor called low-grade renal collecting duct carcinoma. Grossly, the tumor consisted of multiple cysts and solid white nodules, measuring 10 cm in diameter and occupying most of the renal parenchyma. Histologically, the tumor was characterized by well-differentiated tubules lined by eosinophilic cells without papillary projections, abundant predominantly extracellular mucin, minimal cellular atypia, no desmoplasia, and rare mitoses. This tumor occurs in collecting ducts and the tumor cells were positive for epithelial membrane antigen, high-molecular-weight keratin, CD15, and mitochondrial antibody and negative for CD10. Few cells stained weakly positive for ulex europaeus. Ultrastructural study showed a large number of mitochondria according to the eosinophilic cells seen in light microscopy.     

Neuroendocrine carcinoma of the parotid gland: A report of two cases with ultrastructural and immunohistochemical studies

Two cases of primary small cell carcinoma of the parotid gland are reported. This rare neoplasm usually presents as a painful or painless mass in the gland. The finding of neurosecretory granules by electron microscopic study, combined with strong immunoreactivity for neuron-specific enolase and chromogranin, confirms the true neuroendocrine origin of the carcinoma. This tumor appears to have a better prognosis than small cell carcinoma of the lung, which it resembles histologically.     

A histopathological,immunohistochemical and ultrastructural study of intranuclear cytoplasmic inclusions in thyroid papillary carcinoma

Summary Intranuclear cytoplasmic inclusions (ICI) in 38 cases of thyroid papillary carcinoma were studied histopathologically, immunohistochemically, and ultrastructurally in order to examine the frequency of ICI and their relationship to both the histological structure and cytological findings in thyroid papillary carcinoma. The fine-structure and biochemical state of ICI were also studied. ICI occurred in all 38 cases. ICI occurrence ranged from one in several microscopic fields to more than ten per field. The number of ICI divided by the number of nuclei on the microscopic photographs ranged from 0.013 to 0.116. The frequency of ICI was strongly influenced by the state of nuclear chromatin and pleomorphism, but was not influenced by a pattern of papillary or follicular tumour growth. Immunohistochemically, 10-30% of ICI revealed strong thyroglobulin (Tg), which was ascertained by immunoelectron microscopy. Neither T3 nor T4 was detected in ICI (with some exceptions). Some ICI showed keratin and vimentin. PAS-positive ICI were observed. Ultrastructurally, enlarged r-ER, many Golgi vesicles and small vesicles (diameter of 300-500 nm) and sacs were observed in ICI. These findings suggested increased protein synthesis and/or protein accumulation Abundant secondary lysozomes, showing degradation of ICI, and bundles of condensed intermediate filaments were also detected. The character and genesis of ICI are discussed.     

Immunotoxicity of the organochlorine pesticide methoxychlor in female ICR,BALB/c,and C3H/He mice

Several types of pesticides, including organochlorines, are known to suppress or modulate immune responses. The present study evaluated the immunotoxicity of the organochlorine pesticide methoxychlor (MXC) in female BALB/c, C3H/He, and ICR mice. Mice were given oral MXC doses of 0, 30, 100, and 300?mg/kg each day for 7 consecutive days. On day 4, the mice also received an intravenous injection of sheep red blood cells (SRBC). The splenic plaque-forming cell (PFC) IgM response and the serum anti-SRBC IgM antibody titer were evaluated while splenic lymphocytes were counted by flow cytometry and the spleen underwent histopathological analysis. Significant decreases in IgM PFC responses were seen in BALB/c, C3H/He, and ICR mice that received MXC doses of 100 and 300?mg/kg. Similar changes in serum anti-SRBC IgM antibody titers occurred in three strain mice. Flow cytometric analysis revealed significantly decreased splenic T-cell (CD3⁺) populations in a dose dependent manner in BALB/c mice, and in the 300 mg/kg of MXC-treated group of C3H/He mice. Germinal center (GC) B-cell (CD19⁺PNA⁺) populations were significantly decreased in the 300?mg/kg of MXC-treated groups of all three mouse strains and in the 30 and 100?mg/kg of MXC-treated groups of BALB/c and C3H/He strain mice. Histopathological analysis revealed decreased cellularity of the periarteriolar lymphoid sheath (PALS; T-cell area) and decreased GC development in all three strains of mice treated with 300?mg/kg MXC. These results suggest that MXC has an immune-suppressive effect in mice, and that our protocol may be useful for rapidly detecting immunosuppression induced by environmental chemicals.     

Mucinous cystadenoma of the lung. A report of two cases with immunohistochemical and ultrastructural analysis.

We describe two patients who presented with solitary pulmonary masses that consisted of unilocular cysts lined by columnar mucinous epithelium. The cysts contained copious mucus. The epithelial lining of the cysts showed foci of stratification and papillary infolding. Histologically identical lesions have previously been termed unusual mucous cysts or mucinous cystadenomas. We believe that these tumors are true neoplasms differentiating toward the respiratory epithelial mucous cell. They should be distinguished from a variety of pulmonary neoplasms including bronchoalveolar carcinoma, bronchial mucous gland adenoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma.     

Papillary carcinoma of the thyroid. A histochemical, immunohistochemical and ultrastructural study with special reference to the follicular variant

Twenty-one papillary thyroid carcinomas (PTCs), grouped into predominantly papillary (14 cases), predominantly follicular (5 cases), and extremely follicular, i.e., follicular variant (2 cases) types, were studied in comparison with three cases each of follicular lesions including follicular carcinoma, follicular adenoma, adenomatous goiter and Graves' disease. Histochemical, immunoperoxidase, and electron microscopic analyses demonstrated no remarkable differences between the predominantly papillary and predominantly follicular PTCs, but the presence of common characteristics distinct from those of the follicular lesions. These two types of PTCs showed less glycogen, more mucoid material, more epidermal keratin, less thyroid hormone with relative predominance of T3 over T4, and more interdigitating reticulum cells (IDCs) than most of the follicular lesions. Ultrastructurally, the tumor cells of these PTCs had markedly irregular nuclei, a vesicular chromatin pattern, and small basally located lysosomes, in contrast with the cells in the follicular lesions which had smooth round nuclei, more heterochromatin, and apical or dispersed lysosomes of various sizes. The follicular variant PTCs showed some mixed features, such as glycogen in the follicular portion and mucoid material in metastatic papillary foci, positive keratin and IDCs but greater amounts of thyroid hormone, and a rather intermediate type of ultrastructure with only mildly irregular but vesicular nuclei and large apical as well as small basal lysosomes. These findings cytologically support the WHO definition of papillary carcinoma that includes tumors with variable mixtures of papillary and follicular patterns. However, separate consideration may be necessary with regard to the follicular variant.     

Medullary thyroid carcinoma with thyroglobulin immunoreactivity. A special entity?

Fourteen medullary carcinomas of the thyroid (MCT) immunoreactive for both thyroglobulin and calcitonin were studied by light microscopy and immunohistochemistry. Thyroglobulin immunoreactivity was seen in neoplastic follicles and/or in solid foci in the lymph node metastases of two cases. Colocalization of thyroglobulin and calcitonin was found in the same neoplastic cells of eight cases using a double immunostaining method; in three of these (including one with metastases), thyroglobulin was found to be colocalized with calcitonin gene related peptide as well. Our histological and immunohistochemical results support the assumption that MCT with thyroglobulin immunoreactivity is an unusual variant of the multihormone producing MCT and strengthen the hypothesis that a common stem cell is the origin of these tumors. The available clinical data suggest that thyroglobulin-positive MCT carry a better prognosis than thyroglobulin-negative MCT.     

Medullary carcinoma of the thyroid with carcinoid-like features.

AIMS: To show that medullary carcinomas of the thyroid are morphologically indistinguishable from gut carcinoids: the value of histochemistry in their identification and differential diagnosis from metastatic carcinoid tumours to the thyroid and some follicular cell neoplasms. METHODS: 15 thyroid medullary carcinomas with features of gut carcinoids were histochemically studied for the presence of argyrophil and argentaffin granules, and calcitonin, thyroglobulin, and serotonin immunoreaction. RESULTS: Histological features of midgut (classic) carcinoids were observed in two tumours, foregut carcinoids in 12, and hindgut carcinoids in one. All tumours showed, to a greater or lesser extent, a calcitonin immunoreaction and argyrophilia. These markers were present only in a small area showing a classic pattern of thyroid medullary carcinoma in the hindgut carcinoid-like neoplasm. Argentaffin granules and serotonin immunostaining occurred in occasional cells from four foregut carcinoid-like tumours. Thyroglobulin was not expressed in all cases and amyloid stroma was expressed in three. CONCLUSIONS: In some cases a diagnosis of metastatic carcinoid tumour to the thyroid can be considered only after ruling out clinically and histochemically medullary carcinoma of the thyroid. Immunolocalisation techniques are also essential for the differentiation between medullary carcinoma and thyroid follicular cell neoplasms that resemble carcinoid tumours. It is proposed that this tumour variant to be incorporated into current classifications as another histological subtype of C cell carcinoma.     

副神经节瘤样脑膜瘤的临床病理观察

脑膜瘤是较为常见的、发生于脑膜部位的中枢神经系统的肿瘤.脑膜瘤的组织学类型比较多,近年来有文献报道了一种新的脑膜瘤类型.称为"副神经节细胞瘤样脑膜瘤",目前对该种脑膜瘤是否是一种新的类型还有争议[1].我们在外检工作中遇到4例,为了提高对该肿瘤的认识,报道如下,结合文献讨论其临床病理特点及诊断、鉴别诊断要点.     

Urinary bladder neoplasms induced in BALB/c female mice with low doses of 2-acetylaminofluorene

Large numbers of female BALB/c mice were exposed to low levels of 2-acetylaminofluorene (2-AAF) in the diet. The dose response for urinary bladder neoplasms exhibited a shallow trend to low doses which increased sharply at the higher doses. The dose response over the entire dosage range gave the impression of a "threshold" type response below the mid-doses. Since the tumor incidence at the lower doses was less than 1.0 percent, relatively few urinary bladder tumors occurred. Thus, it was deemed advisable to re-examine noninvasive or early invasive bladder carcinomas and to study the dose response for only the "unequivocal" urinary bladder tumors. Examination of the dose response curves for "unequivocal" urinary bladder tumors showed a positive trend over the low end of the dose range. As a further check, an analysis was conducted on only invasive or metastasizing bladder carcinomas. In this case, there was no significant low dose trend. Thus, the shape of the low dose response curve for bladder carcinomas remains uncertain.     

Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and ultrastructural study of four cases.

We present the clinical, histologic, immunohistochemical, and ultrastructural findings of four cases of non-functioning oncocytic adrenocortical carcinomas. The patients' ages ranged from 39 to 71 years. There was no sex predilection. Large yellow-tan tumors (8.5 to 17.0 cm), well demarcated from the adjacent kidney, were seen with a thin rim of normal adrenal gland along one edge. One tumor invaded the inferior vena cava and extended up to the level of the right atrium, and another metastasized to bone. The other two tumors had similar morphologic features and therefore were considered carcinomas. Histologic sections of all four cases showed a diffuse proliferation of polygonal neoplastic cells with large nuclei containing prominent nucleoli and abundant granular and eosinophilic cytoplasm. Occasional mononuclear and binucleated giant cells were noted in one case. There were rare mitotic figures (less than one per 10 high power fields). All tumors were immunoreactive for cytokeratins (AE1/AE3 and CAM5.2). Inhibin was focally expressed by one tumor and its bone metastasis. Ultrastructurally, the cytoplasm of the neoplastic cells was packed with innumerable mitochondria. Cytologic atypia or mitotic rate cannot reliably predict the biologic behavior of oncocytic adrenocortical neoplasms. Large tumor size (4/4), extracapsular extension (3/4), blood vessel invasion (2/4), necrosis (4/4), and metastasis (1/4) are features of malignancy for oncocytic adrenocortical carcinomas. The treatment of these tumors is complete surgical excision.     

C-cell hyperplasia and medullary thyroid carcinoma in the rat. An immunohistochemical and ultrastructural analysis.

Medullary thyroid carcinoma (MTC) is a distinctive neoplasm which is derived from the calcitonin-producing intrathyroidal C-cell system and which develops commonly in untreated rats of various strains. Thyroid glands of Long-Evans rats ranging in age from 3 months to 3 years showed a spectrum of C-cell proliferative abnormalities. As compared to 3-month-old control rats, thyroids from 9- to 12-month-old animals exhibited mild diffuse C-cell hyperplasia (CCH). Thyroids from animals ranging from 1 to 3 years of age exhibited progressively more severe C-cell abnormalities including severe diffuse CCH, nodular CCH, and/or MTC. In contrast to the normal basal serum calcitonin levels in controls and in animals with mild diffuse CCH, animals with severe diffuse CCH, nodular CCH, or MTC had elevated basal serum calcitonin values. Nodular CCH was characterized by the replacement and enlargement of individual follicles by C-cells. Larger foci of nodular CCH were characterized by similar changes in multiple adjacent follicles or by an irregular expansion of individual follicles. MTC was characterized by penetration of the follicular basal lamina by C-cells with extension into the adjacent thyroid stroma. In addition to the high incidence of thyroidal C-cell abnormalities, diffuse and/or nodular parathyroid hyperplasia was commonly found. There was no evidence of chronic renal failure in these animals, and the serum calcium levels were within normal limits. Although the stimulus for the initial C-cell proliferation remains unknown, the appearance of MTC is preceded by relatively prolonged phases of CCH. These findings are essentially identical with those noted in human familial MTC and indicate that the rat provides a useful model system for studying the regulation of C-cell proliferation during the processes of neoplastic development and progression.     

Experimental production of actinomycetoma in BALB/c mice.

Chronic actinomycetoma associated with grain production was induced in BALB/c mice by subcutaneous inoculation of live Nocardia brasiliensis in Freund incomplete adjuvant into the hind footpads. Similar inoculation of N. asteroides and N. caviae resulted in local tumor formation which healed spontaneously after 5 months, the disease disseminating into the peritoneum, where masses or organisms could be detected. Grains were recovered from superficial skin lesions of N. caviae, but not from the N. asteroides-infected mice. Mycetoma lesions, appearing as early as 1 month after inoculation of 1.2 X 10(7) colony-forming units of N. brasiliensis per ml or as late as 3 months with inoculation of 1.0 X 10(5) colony-forming units per ml, became persistent and were readily detectable even 6 months after inoculation. No spontaneous healing occurred, and grains were recovered at different stages of the disease. Saline suspensions of N. brasiliensis also produced typical mycetoma lesions, although the incubation period was ca. 6 months. Adjuvant addition appeared to accelerate the onset of the disease. Experimental production of actinomycetoma in laboratory animals allows the study of many unanswered aspects of the disease and also provides a suitable model for therapeutic trials in the search for new and more effective chemotherapeutic agents.     

Early ultrastructural changes in the biliary epithelial cells of BALB/c and DDY mice immunized with swine serum

Electron microscopic observations were carried out on the biliary epithelial cells of BALB/c and DDY mice which had received an intraperitoneal injection of 0.2 ml of swine serum twice a week for 2 or 4 weeks. The most characteristic feature of the biliary epithelial cells of BALB/c mice was a marked increase in the number of vesicles having a close spatial relationship with the well-developed Golgi apparatus or rough endoplasmic reticulum (rER). In contrast, marked dilation of rER filled with moderately electron-dense material was conspicuous in the biliary epithelial cells of DDY mice. A prominent increase in the number of blebs and lateral and basal cytoplasmic protrusions in the dilated intercellular space of the biliary epithelium, and submucosal eosinophil infiltration, collagen fiber proliferation and gland hyperplasia with increased mucin secretion were common to both strains. This experimental model of bile duct disease also seems to be useful for investigating alteration of protein synthesis and secretion in epithelial cells.     

Secretory meningioma--a case report with histopathological,immunohistochemical and ultrastructural analysis.

Secretory meningioma have been described as a distinct variant of meningioma based on their histologic, immunohistochemical and ultrastructural features of epithelial and secretory differentiation of meningothelial cells with accumulation of secretory material in the form of hyaline inclusion. Secretory meningioma is also a benign tumor having similar biological behaviour to that of typical meningiomas: hence, it is important for it to be recognized and diagnosed correctly to avoid unnecessary radiation and chemotherapy. Here we present a case of secretory meningioma with typical morphologic features. The patient was a 56-year-old woman with bilateral visual disturbance. A well-circumscribed mass was present in the left frontal lobe of cerebrum with surrounding edema. The tumor was composed of whorls of meningothelial cells and abundant intra- and extracellular eosinophilic hyaline inclusions which showed immunoreactivity for epithelial membrane antigen(EMA) and carcinoembryonic antigen(CEA). Ultrastructural features also supported epithelial and secretory differentiation of tumor cells.     

Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

Organ tissue damage is a key contributor to host morbidity and mortality following infection with microbial agents. Severe immune responses, excessive cellular recruitment and necrosis of cells all play a role in disease pathology. Understanding the pathogenesis of disease can aid in identifying potential new therapeutic targets or simply act as a diagnostic tool. Burkholderia pseudomallei is a Gram‐negative bacterium that can cause acute and chronic diseases. The BALB/c mouse has been shown to be highly susceptible to aerosol challenge with B. pseudomallei and hence acts as a good model to study the acute and potentially lethal form of the disease melioidosis. In our study, BALB/c mice were challenged and culled at predetermined time points to generate a pathological time course of infection. Lung, liver and spleen were subjected to pathological and immunohistochemical analysis. The number and type of microscopic lesions within each organ, as well as the location and the mean percentage of neutrophils, B cells, T cells and Burkholderia capsule antigen within the lesions, were all characterized during the time course. Neutrophils were determined as the key player in tissue pathology and generation of lesions, with B cells playing an insignificant role. This detailed pathological assessment increases our understanding of B. pseudomallei disease.     

Oestrus cycle perturbations and hypotrophy of clitoral glands in malaria-infected female BALB/c mice

An experimental host-parasite association involving BALB/c female mice infected with Plasmodium vinckei petteri was used with the aim of investigating the morphological and physiological alterations induced by the parasite in the genital tract of the host. The vaginal oestrous cycle was monitored as a daily clue to the sexual physiology of the female mice, and a complete histological analysis of the genital tract was performed 36 days following parasite inoculation. The oestrous cycle showed strong transitory alterations during the first 30 days following infection. The occurrence of oestrus days increased during the first 10 days post-infection and then decreased to a subnormal value during the following 20 days. Infected mice also showed a remarkable hypotrophy of their clitoral glands 30 days after the beginning of the malarial infection. A probable cause of such perturbations is a significant hormonal imbalance triggered by the erythrocytic proliferation of the Plasmodium. The relationship between the immune response of the host and these physiological and morphological alterations, as well as the outcomes of these alterations on the sexuality of the rodent host are discussed.     

Inoculation of BALB/c mice with fish-pathogenic nodaviruses

To investigate the pathogenicity of fish-pathogenic nodaviruses (betanodaviruses) in mammals, weanling mice were inoculated with striped jack nervous necrosis virus (SJNNV; the type species of the genus Betanodavirus) or redspotted grouper nervous necrosis virus (RGNNV), which belong to different genotypes. After inoculation with 10(7.5) TCID50, either intramuscularly or intraperitoneally, mice remained clinically normal for the 14-day observation period. In a subsequent short-term (72 h) experiment, mice inoculated intramuscularly with 10(7.5) TCID50 yielded virus (10(6) to 10(5) TCID50/g) from muscle at the site of injection at 3, 24 and 72 h post-infection; they also yielded virus from the kidneys (10(5) TCID50/g) at 3 and 24 h post-infection, but by 72 h virus had become almost undetectable at this site. Throughout the experiment, no virus was detected in the sites that are target organs of betanodaviruses in fish, namely, the brain, spinal cord and eye. The results indicate that the mouse is not susceptible to betanodaviruses.