Malignant renal rhabdoid tumour. Immunohistochemical and ultrastructural studies

In an effort to establish their possible histogenesis, three cases of renal rhabdoid tumour and their metastases were studied both by a battery of polyclonal and monoclonal antibodies using the avidin-biotin-peroxidase complex technique and by electron microscopy. Vimentin was demonstrated in renal rhabdoid tumour in two cases and in all metastatic deposits. Cytokeratin (39, 43 and 50 kD) was not demonstrable in the three renal rhabdoid tumours, but was strongly positive in all metastatic lesions in one case. Epithelial membrane antigen was present in one renal rhabdoid tumour and in pulmonary metastases in two cases. Ultrastructural study showed epithelial differentiation in all tumours: basal lamina and convergent tight junctions were demonstrated; intracytoplasmic intermediate filaments were present in all primary and metastatic tumours. Rhabdoid tumours thus exhibited heterogeneous immunophenotypic expression suggesting that they are derived from mesenchymal cells which are capable of differentiating into epithelial cells.     

Malignant rhabdoid tumour of the liver. A case report

A case of primary malignant rhabdoid tumour of the liver occurring in a 5-month-old girl is reported. Histologically the neoplasm presented the 'typical' features as described in malignant rhabdoid tumour arising in the kidney. In addition, some areas of the tumour showed a 'pseudoglandular' growth pattern. Immunohistochemistry revealed the neoplastic cells to be intensively positive for vimentin and for cytokeratin 19. Variable immunoreactivity for cytokeratin polypeptides 7, 8 and 19 was also detected. On electronmicroscopy the neoplastic cells contained bundles of intermediate filaments, tonofilaments and intercellular junctions. These findings are suggestive of a primitive epithelial differentiation.     

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.     

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.     

Malignant rhabdoid tumor of the vulva: Case report with cytological, immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature

A case of malignant rhabdoid tumor of the vulva in a 25-year-old female was examined. The patient presented with a subcutaneous nodule in the lefl labium majus. Smears of the material obtained by percutaneus fineneedle asplratlon demonstrated clusters of atypical cells with prominent nucleoli. The tumor measured 6 × 5 × 5 cm and appeared tan to brown on the cut surface and partly cystlc. Pathological findings obtalned from intraoperative frozen tlssue sections had been originally interpreted as rhabdomyosar-coma. Light microscopic examination revealed that polyge nal tumor cells having vesicular nuclei with prominent nucleoli were arranged in sheets and the great majority of the tumor cells contained an eosinophillc globular paranu-clear cytoplasmic Inclusion. Ultrastructurally, this cytoplas-mic inclusion corresponds to whirls of intermediate filaments. Vlmentln immunoreactlvity was detected in both the cytoplasm and cytoplamic inclusion of almost all the tumor cells. No cytokeratin and desmin immunoreactivlty were detected In the tumor cells. The Ki-67 labeling index was 36% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA Index = 0.95).     

Primitive neuroectodermal tumour of the central nervous system associated with malignant rhabdoid tumour of the kidney: report of a case

Malignant rhabdoid tumour of the kidney is a recently reported tumour presenting in young children. Irrespective of stage and despite intensive chemotherapy these tumours have a poor prognosis, with death usually occurring within a matter of months. A recent report has shown the association of second embryonal tumours of the central nervous system occurring in patients with the renal tumour; most of these second tumours have occurred in the posterior fossa. We report here an infant who presented with a mass in the right groin, showing features of a poorly differentiated sarcoma, possibly rhabdomyosarcoma. Further investigations revealed a tumour in the lower pole of the right kidney which was subsequently shown to be a malignant rhabdoid tumour. The child was given chemotherapy but re-presented at 10 months of age with hydrocephalus, irritability and spasms leading to death. At autopsy a large tumour was found filling the right lateral and third ventricles; histology showed a primitive neuroectodermal tumour with focal astrocytic differentiation. Residual rhabdoid tumour was restricted to a few para-aortic lymph nodes and focal lymphatic micrometastases in lungs. The association of two embryonal neoplasms of possible similar histogenesis is discussed.     

Malignant myoepithelioma of the breast

Malignant myoepithelioma of the breast is rare. A 50-year-old Japanese woman was admitted to our hospital because of a right breast tumor (11 × 10 × 5.5 cm). Core needle biopsy revealed malignant spindle cells. A mastectomy was performed. The tumor consisted of malignant spindle, round, pleomorphic and giant cells with many mitotic figures and necrotic areas. Tumor and osteoclast-like giant cells were scattered. Much lymphovascular permeation was seen. In a few areas, particularly on the tumor periphery, there were merges between the tumor cells and myoepithelial cells of the non-tumorous ducts, as if the tumor emanated from the duct myoepithelium. The tumor was invasive into the skin and pectoral muscle. Immunohistochemically, the tumor cells were diffusely positive for vimentin, CD10, α-smooth muscle antigen, and Ki-67 (labeling = 95%). The significant areas of the tumor were positive for S100 protein, p63, p53, CD68, caldesmon, desmin and TGFβ1. A few areas were positive for pancytokeratin (AE1/3), cytokeratin (CK) 5/6, and CK 34βE12. In contrast, the tumor cells were negative for pancytokeratins (WSS, CAM5.2), CK7, CK8, CK14, CK18, CK19, CK20, EMA, CEA, bcl-2, myoglobin, CD34, CD56, CD45, HMB45, GFAP, α-1-antitrypsin, synaptophysin, estrogen receptor, progesterone receptor, HER2/neu, MUC1, MUC2, MUC5AC and MUC6. The author diagnosed the tumor as malignant myoepithelioma, as myoepithelial markers (C10, p63, S100 protein, α-smooth muscle actin, caldesmon) were positive, and also because there was a transition between the tumor cells and myoepithelium of non-tumorous ducts. The grade of the tumor was high. The patient was treated with chemoradiation and was free of disease 5 months after the operation.     

Diagnosis of distal 22q11.2 deletion syndrome in a patient with a teratoid/rhabdoid tumour

We report an 18 year old patient with mild intellectual disability who was diagnosed with a late onset teratoid/rhabdoid tumour by histological and immunohistochemical studies. Array-CGH studies, performed on a peripheral blood sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumours. Although several constitutional chromosome conditions are known to have increased susceptibility to various forms of cancer, very little is known regarding the magnitude of risk for malignancy associated with distal 22q11.2 deletion syndrome. In view of this finding we suggest that patients diagnosed with distal 22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of tumour. This case demonstrates the need to carefully assess regions found to be deleted in individuals, referred for dysmorphia and/or developments delay, by array-CGH for the presence of genes known to be implicated in malignancy.     

Malignant myoepithelioma of the breast: a case report and review of literature

In this article, we described a malignant myoepithelioma of the breast (MMB) in a 69-year-old woman. Breast cancer derived from myoepithelial cells is very rare, usually benign. The diagnosis of MMB based on histological and immunohistochemical finding. In this case, the author diagnosed the tumor as MMB, because tumor tissues were immunopositive for 34βE12, P63, SMA, S-100, CD10, E-Cad and Ki-67, and immunnegative for CK5/6, desmin, ER, PR and C-erbB-2, because tumor tissue showed invasive growth and local hemorrhage or necrosis, suggesting malignant, and also because there was a transition between the tumor cells and hyperplastic myoepithelium of non-tumorous ducts. The patient’s postoperative recovery is smooth and regular following of patient is essential.     

Malignant rhabdoid tumour of soft tissue. An ultrastructural and immunohistological study of a pelvic tumour

A case of extrarenal malignant rhabdoid sarcoma arising in the pelvic soft tissues of a 12-year-old girl is described. By routine light microscopy the tumour resembled, in some areas, an embryonal rhabdomyosarcoma and, in other areas, a neuroblastoma. Electron microscopy revealed characteristic cytoplasmic aggregates of intermediate filaments, often with central clusters of organelle membranes surrounded by these filaments. Immunohistochemical stains showed strong cytoplasmic reactivity for vimentin. Staining for cytokeratin, myoglobin, desmin, neurofilaments, neurone specific enolase, S-100 protein and leucocyte common antigen was negative. A histogenetic origin from primitive mesenchymal cells is favoured. We strongly support the use of electron microscopy for the definitive diagnosis of small round cell undifferentiated sarcomas of childhood.     

Malignant rhabdoid tumor of the prostatic region

Summary We describe a malignant rhabdoid tumour of the prostatic region in a 14-year old boy. The tumour showed positive immunoreactivity for epidermal prekeratin, monoclonal cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and monoclonal vimentin but was negative for myoglobin, alfa-fetoprotein and lysozyme. Electron microscopy revealed pleomorphic cells with collections of paranuclear intermediate filaments, sheaves of tonofilaments and abundant microvilli in some tumour cells. Epithelial derivation was also suggested by occasional intracytoplasmic lumina and rare cell junctions.     

Malignant myoepithelioma of the breast metastasizing to the jaw

A breast tumor in a 52-year-old female was interpreted as a malignant myoepithelioma based on morphological and immunohistochemical studies. The tumor consisted of elongated cells with clear cytoplasm and lacked glandular components. The tumor cells were stained positively for keratin, S-100 protein, glial fibrillary acidic protein (GFAP) and muscle-specific actin. Distant metastasis in the right jaw developed 8 years after the initial surgery and the metastatic deposit showed a similar morphology and immunoreactivity. Myoepithelial tumors are generally considered as benign or low-grade lesions and distant metastasis has been rarely documented. The present case presents the possibility of delayed occurrence of distant metastasis in myoepithelial tumor of the breast. Received: 22 January 1999 / Accepted: 18 May 1999     

Malignant myoepithelioma of salivary glands: Clinicopathological features of ten cases

Malignant myoepithelioma of the salivary gland is discussed in terms of its clinical behaviour, morphological features and the frequent pre-existence of a pleomorphic adenoma. The study comprised six female and four male patients aged 14–63 years (mean age 38.9 years). Two tumours presented as intraoral lesions and eight were located in the parotid gland. Tumour cells displayed a morphological spectrum ranging from round epithelioid cells to spindle-shaped and stellate cells. Most cells displayed reactivity for high molecular weight keratins and in four tumours there was strong immunoreactivity for smooth muscle actin. Malignant myoepithelioma seems to arise in two different clinical settings: either de novo or in a recurrent pleomorphic adenoma. De novo malignant myoepitheliomas arise in normal salivary gland, tend to be more aggressive and have a short clinical history. Recurrences may not develop or may occur as a single event within a short time interval, and métastases develop in the lungs. Malignant myoepitheliomas arising in recurrent pleomorphic adenomas have a long clinical history, are characterized by multiple recurrences and have to be distinguished from aggressive carcinomas arising in these adenomas. In contrast, the tumours described in the present series arising in pleomorphic adenomas showed local aggressiveness and metastases did not occur until decades after the first treatment. The general opinion that all malignant tumours that arise from pleomorphic adenomas are highly aggressive is not confirmed by the present study.     

Familial rhabdoid tumour 'avant la lettre'—from pathology review to exome sequencing and back again

Here we provide compelling evidence that next‐generation sequencing will revolutionize diagnostics. We reappraised a case from 1991, published in 1993, describing the unique occurrence of an ovarian immature teratoma arising in a young woman and a clonally distinct intracerebral immature teratoma developing in her daughter. We conducted whole‐exome sequencing on constitutional DNA from the mother and her daughter and identified a previously unreported nonsense mutation (c.3533G>A; p.Trp1178^*) in the chromatin remodelling gene, SMARCA4, that was present in both individuals and was subject to nonsense‐mediated decay. Tumour analysis by Sanger sequencing revealed a somatic SMARCA4 mutation in both the mother (c.2438+1G>T) and her daughter (c.3229C>T; p.Arg1077^*), which are predicted to be truncating. As immature teratomas are classified as germ cell tumours, we performed a comprehensive mutation survey of 106 apparently sporadic germ cell tumours, but did not find any other clearly deleterious SMARCA4 mutations. Recently, inactivating mutations in SMARCA4 have been found in two cases of rhabdoid tumour predisposition syndrome type 2. In the light of these findings, renewed efforts to locate previously unobtainable tumour samples were successfully undertaken. Histopathological and immunohistochemical re‐analysis of the daughter's tumour revealed that it was indeed a rhabdoid tumour (atypical teratoid/rhabdoid tumour). In this context, the original pathology report of the mother's ovarian tumour was re‐interpreted as describing a malignant rhabdoid tumour of the ovary. This report raises the question as to whether molecular genetic analysis should be included in tumour classification, alongside more traditional microscopy‐based methods. The use of new sequencing technologies, particularly when applied to archived samples, will lead to many more 'molecular rediagnoses'. This is the earliest known case of rhabdoid tumour predisposition syndrome type 2 and the first described case with an autosomal dominant pattern of inheritance, only discovered through an exome sequencing project. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.