A novel case of rhabdoid colon carcinoma associated with a positive CpG island methylator phenotype and BRAF mutation

Colon carcinoma with rhabdoid characteristics is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a colon adenocarcinoma with rhabdoid features in a 71-year-old woman, localized to the right colon and associated with local lymph node and liver metastasis. The patient died within 8 months from surgery despite target chemotherapy. The tumor was enriched in cells with a typical rhabdoid-type morphology displaying a marked and diffuse vimentin staining. Cells were also positive for epidermal growth factor receptor (EGFR), p53, Ki67, and β-catenin and negative for cytokeratin 20/cytokeratin 7, E-cadherin, and CDX2. Remarkably, the promoter regions of 4 of 5 specific genes that define the so-called "CpG island methylator phenotype," including mutL homolog 1 (MLH1), were methylated. Consistently, microsatellite instability was detected. A BRAF V600E mutation and no KRAS mutations were identified. Finally, 4 tumor suppressor gene promoters CDH1, CDKN1B, CDKN1C, and MGMT were not methylated. This is the first case of a colorectal carcinoma with rhabdoid features, "CpG island methylator phenotype," high microsatellite instability associated with a BRAF mutation, and patient poorer outcome.     

Follicular thyroid carcinoma with rhabdoid phenotype

The aim of this paper is to highlight the occurrence of an unusual histological variant of follicular carcinoma of the thyroid. Three cases are presented: each of the tumours contained a significant population of rhabdoid cells (accounting for 30–40% of the total tumour content). They were all found in female patients aged 65, 43 and 56 years, who presented with enlarged thyroid glands and were subjected to lobectomies. The tumours contained foci of well-differentiated follicular carcinoma, with areas of capsular and vascular invasion, and an accompanying rhabdoid cell component that merged with the neoplastic follicles. Immunohistochemically, the follicular component was positive with thyroglobulin, but the rhabdoid cells were negative in all three cases. The cytoplasmic aggregates in the rhabdoid cells were strongly positive for epithelial markers and vimentin. Two tumours pursued an aggressive biological course similar to other composite extrarenal rhabdoid tumours. A rhabdoid component accompanying thyroid follicular carcinomas is an adverse prognostic factor. Received: 21 October 1998 / Accepted: 5 May 1999     

Uterine leiomyomas with inclusion bodies: an immunohistochemical and ultrastructural analysis of 12 cases

We describe 12 cases of leiomyoma with intracytoplasmic inclusion bodies, which were detected in a group of 447 leiomyomas examined at our institution between December 2005 and March 2006. Ten of these tumors were typical leiomyomas, and two cases represented atypical (bizarre) leiomyoma. In some cases, the presence of intracytoplasmic inclusion bodies resulted in a rhabdoid or skeletal muscle-like appearance of the tumor cells. Ultrastructurally, there were two types of inclusions. One of them consisted of an abnormal aggregation of intermediate and actin filaments. Another type of inclusions was composed of dense granular material without an apparent fibrillar structure. The ultrastructure of the inclusions correlates with immunohistochemical and histochemical stainings. The inclusions with apparent fibrillar arrangements were PAS negative, stained red by trichrome, and were, at least at the periphery, actin-, desmin-, and h-caldesmon-positive. The dense granular inclusions were at least focally PAS-positive, stained red by trichrome, and were negative immunohistochemically. The intracytoplasmic inclusions were found in atypical (bizarre) leiomyomas of the uterus and occasionally in epithelioid leiomyomas and leiomyosarcomas. However, to the best of our knowledge, these inclusions have not been found in typical uterine leiomyomas to date.     

Papillary thyroid carcinoma with anaplastic transformation showing a rhabdoid phenotype solely in the cervical lymph node metastasis

We describe a rare case of anaplastically transformed papillary thyroid carcinoma with a rhabdoid phenotype appearing solely in a metastatic focus. A 77-year-old man presented with a rapidly enlarging, painful right lateral cervical mass. CT scan revealed a tumor in the right upper pole of the thyroid gland and a right lateral cervical mass. Examination of surgically resected specimens disclosed that the thyroid tumor was a well-differentiated papillary carcinoma (2.0 cm in diameter), and the right lateral cervical mass was an anaplastic carcinoma (2.4 cm in diameter) showing a rhabdoid phenotype with scant amounts of a papillary carcinoma component in the periphery, considered to be transformed through the metastasis of the papillary thyroid carcinoma in a cervical lymph node. The rhabdoid cells had eccentric nuclei with conspicuous nucleoli and spherical hyaline cytoplasmic inclusions, which are immunoreactive for vimentin and sarcomeric actin. Ultrastructurally, these had globular aggregation of thin and intermediate filaments. Nuclear immunoreactivity for INI1 indicated that the tumor had no INI1 abnormalities, suggesting a secondary rhabdoid tumor. Recurrence developed in the right cervical and mediastinal lymph nodes, and the patient died of disease 6 months after surgery. A rhabdoid phenotype is a pathological hallmark indicating the aggressive nature not only in the neck region, but also in other organs.     

Gastrointestinal stromal tumor of the stomach with rhabdoid phenotype: immunohistochemical, ultrastructural, and immunoelectron microscopic evaluation

A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination.     

Cecal adenocarcinoma with prominent rhabdoid feature: report of a case with immunohistochemical, ultrastructural, and molecular analyses

Colorectal adenocarcinoma with rhabdoid phenotype is extremely rare, and only 1 case of adenocarcinoma showing rhabdoid dedifferentiation has been reported. The authors present another case of cecal adenocarcinoma with prominent rhabdoid feature in a 66-year-old man. The 13-cm sized tumor consisted mainly of rhabdoid cells and partly of adenocarcinoma, and transition from adenocarcinoma to rhabdoid areas was noted. Ultrastructural analysis revealed intracytoplasmic aggregates of intermediate filaments in the rhabdoid cells. Adenocarcinoma cells were diffusely immunoreactive to cytokeratin 7 and AE1/3, but occasionally positive for vimentin. The rhabdoid cells were negative for cytokeratin 7, weakly/focally immunoreactive to AE1/3, and diffusely positive for vimentin. These results suggested that the rhabdoid cells were dedifferentiated adenocarcinoma. Analysis of the rhabdoid cells with molecular techniques is also presented.     

Fine-needle aspiration cytology of pulmonary adenocarcinoma of fetal type: report of a case with immunohistochemical and ultrastructural studies.

This report describes the fine-needle aspiration (FNA) cytology of a case of adenocarcinoma resembling fetal lung in a 53-yr-old male, a very uncommon malignant tumor of the lung that is similar to an early stage of lung differentiation. FNA smears revealed relatively small, fairly uniform tumor cells appearing as cohesive cell groups and scattered, isolated cells, some of them showing a rosette or acinus pattern. In addition, clusters of larger cells with eosinophilic cytoplasm and prominent nucleoli existed contiguously with the small cells or separately. The possibilities of an unusual type of adenocarcinoma, carcinoid tumor, and pulmonary blastoma were suggested by the cytologic findings. Immunohistochemical studies performed on a resected tumor tissue showed immunoreactivity for alpha-fetoprotein, neuron-specific enolase, and somatostatin, and endocrine-type granules were found ultrastructurally. This type of adenocarcinoma is considered to have a histogenesis similar to that of pulmonary blastoma. To our knowledge this is the first reported case in the cytologic literature.     

伴横纹肌样特征的肺癌1例报道及文献复习

目的报道1例伴横纹肌样特征的肺癌,并复习相关文献。方法石蜡包埋组织连续切片分别做HE染色、Alcianblue黏液组化染色和免疫组化染色,光镜观察。结果肿瘤突出于右上肺支气管腔,HE染色显示在差分化癌组织中可见横纹肌样特征的癌细胞,约占30%,其细胞质丰富,细胞质内可见明显的嗜酸性包涵体,细胞核偏位,可见核仁。癌组织黏液染色阴性。免疫组化染色显示,vimentin和p63呈弥漫性强阳性,CKpan、CAM5·2、TTF-1和synaptophysin呈灶性阳性,嗜酸性包涵体对CAM5·2呈阳性反应,CEA、chromograninA、SCLC、myoglobin及desmin阴性。结论伴横纹肌样特征的肺癌是原发性肺癌少见的特殊亚型,可存在于差分化非小细胞肺癌中,并可显示灶性神经内分泌分化。     

An ultrastructural and immunohistochemical study of cutaneous metastasis of biliary system carcinoma

An 81-year-old Japanese man noticed red papules and subcutaneous tumors on his face and trunk about 2 months before entering our clinic. He had been suffering from biliary system cancer for about one year.Light microscopic findings: Tumor cells, which formed various-sized glands lined by columnar cells, were observed in the dermis and subcutaneous tissue.Electron microscopic findings: In tumor cells, intracytoplasmic lumina lined with microvilli were observed. Cell organelles, such as mitochondria and rough-surfaced endoplasmic reticulum, were relatively well-developed. From these findings, it seems that the characteristics of these tumor cells resemble those of the biliary system.     

Malignant soft tissue neoplasms with the histologic features of renal rhabdoid tumors: An ultrastructural and immunohistochemical study

Five round cell neoplasms of the soft parts that histologically resembled malignant rhabdoid tumors of the kidney were studied. The tumors were composed mainly of poorly differentiated round or, sometimes, polygonal cells, with a minority of elongated cells; the cytoplasm of many of the cells contained filament-laden acidophilic inclusions. Ultrastructurally, the intracytoplasmic structures were seen to consist of aggregates of 10-nm intermediate filaments, and immunohistochemical staining revealed the presence of cytokeratin and vimentin. All five patients with this tumor had an aggressive clinical course; three of the patients died shortly after the initial diagnosis. As this tumor does not seem to be linked to any known entity, it is referred to as malignant rhabdoid tumor of the soft parts and could be a heterogeneous entity.     

Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases.

Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15-75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-keratin and vimentin in all 10 cases, for keratin 7 in eight of eight, for calretinin in nine of 10, and for keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.     

Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.     

Female urethral adenocarcinoma with a heterogeneous phenotype

We here report a very rare case of female urethral adenocarcinoma. A 77-year-old woman presented with urinary retention. Cystoscopy showed a urethral tumor and the biopsy material showed adenocarcinoma. Macroscopically, the tumor measuring 3.0 x 3.0 x 2.4 cm was predominantly observed around the periurethral area on the proximal side. Histologically, patterns of columnar/mucinous adenocarcinoma, clear cell adenocarcinoma and papillary/micropapillary carcinoma were observed, but there was no evidence of a cribriform pattern. Immunohistochemically, neoplastic cells of at least one of three components were positive for CK7 and CK20 or CA125. We suggest that female urethral adenocarcinoma with a histologically and immunohistochemically heterogeneous phenotype may originate from cells within urethral or paraurethral tissue, such as urethritis glandularis or intestinal metaplastic epithelium and Mullerian tissue.     

Malignant rhabdoid tumour of the uterus: an immunohistochemical and ultrastructural study

Summary Malignant rhabdoid tumours (MRTs) are highly aggressive neoplasms which most frequently occur in the kidney of young children. Several cases of primary MRT occurring in extra-renal sites have been reported, particularly in the soft tissues. We report a case of primary MRT of the uterus, a very rare site for this neoplasm, with morphological, immunohistochemical and ultrastructural features corresponding to restrictive morphological criteria for MRT. The possible differential diagnoses were considered.     

Mucinous colorectal adenocarcinoma with signet-ring cells: immunohistochemical and ultrastructural study

A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as revealed after histological evaluation, was examined ultrastructurally. The authors also analyzed the immunohistochemical data of the tissue for serotonin, vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon, using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling method for light and electron microscope, respectively. Electron microscopically mucinous adenocarcinoma was characterized by the formation of small lumen. Adenocarcinoma cells were full of mucous granules of varying electron density, providing a good environment for the tumor cells to grow. They also exhibited a significant loss of microvilli and intracytoplasmic junctions, which could allow the cells to disseminate. Signet-ring cells were located in the basal site of the ducts or in the lamina propria and appeared neoplastic, with mucin accumulation intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic organelles were decreased and at the periphery of the cell. The PAP method demonstrated that these cells were strongly positive for bombesin and also positive for vasointestinal polypeptide (VIP). The immunogold method detected bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic membranes, whereas VIP was localized mainly in the plasma membrane. The location of signet-ring cells combined with the immunoreactivity for bombesin and VIP indicated that signet-ring cells were of neuroendocrine origin and probably dedifferentiated enterochromaffin-like endocrine cells. These findings have implications for understanding the biological behavior of these composite malignant tumors and could help in the knowledge of the origin of signet-ring cells.     

Prostatic stromal sarcoma with rhabdoid features

Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis).     

Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants

Cartilage engineering is a strategic experimental goal for the treatment of multiple joint diseases. Based on the process of embryonic chondrogenesis, we hypothesized that cartilage could be engineered by condensing chondrocytes in pellet culture and, in the present study, examined the quality of regenerated cartilage in direct comparison with native cartilage. Chondrocytes isolated from the sterna of chick embryos were cultured in pellets (4 x 10(6) cells per pellet) for 2 weeks. Cartilage explants from the same source were cultured as controls. After 2 weeks, the regenerated cartilage from pellet culture had a disc shape and was on average 9 mm at the longest diameter. The chondrocyte phenotype was stabilized in pellet culture as shown by the synthesis of type II collagen and aggrecan, which was the same intensity as in the explant after 7 days in culture. During culture, chondrocytes also continuously synthesized type IX collagen. Type X collagen was negatively stained in both pellets and explants. Except for fibril orientation, collagen fibril diameter and density in the engineered cartilage were comparable with the native cartilage. In conclusion, hyaline cartilage engineered by chondrocytes in pellet culture, without the transformation of cell phenotypes and scaffold materials, shares similarities with native cartilage in cellular distribution, matrix composition and density, and ultrastructure.     

Malignant rhabdoid tumour of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin

A malignant rhabdoid tumour of the bladder is reported from a girl aged 6. Detailed immunohistochemical and ultrastructural investigations provide evidence which suggests a histiocytic origin for this controversial neoplasm.     

Parachordoma: An ultrastructural and immunohistochemical study

A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6- sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.