Yuko Ohjimi

Sarcomatoid carcinoma of the urinary bladder: A clinicopathologic and immunohistochemical analysis of 14 patients

Sarcomatoid carcinoma of the urinary bladder is a rare entity, in which both the histogenesis and biological behavior remain controversial. We herein describe the clinicopathologic and immunohistochemical profiles of sarcomatoid carcinomas and discuss the significance of cell adhesion molecules in the development of this peculiar neoplasm. The authors examined formalin-fixed and paraffin-embedded tissue samples from 14 patients with sarcomatoid carcinoma of the urinary bladder. An immunohistochemical analysis was performed by using antibodies against epithelial and mesenchymal antigens as well as adhesion molecules. Most patients suffered from an advanced stage of the tumor, extending to the muscular layer (7 cases) or to the perivesical tissues (5 cases). Microscopically, all 14 tumors were composed predominantly of a carcomatoid component and an obviously carcinomatous component. The sarcomatoid component was composed of a mixture of spindle cells, round cells, and pleomorphic giant cells. The carcinomatous components consisted of papillary or nonpapillary high-grade transitional cell carcinoma (TCC). The zones of gradual transition between the carcinomatous and the sarcomatous elements were focally apparent in each tumor. The findings of an immunohistochemical examination indicated that both carcinomatous and sarcomatoid components expressed epithelial antigens (pankeratin or EMA), even though the staining pattern varied from case to case. As for cell adhesion molecules, the carcinomatous components were positive for E-cadherin (8 of 12), CD44s (8 of 12), and CD44v6 (6 of 12). Although the sarcomatoid components were also positive for E-cadherin (5 of 12), CD44s (4 of 12), and CD44v6 (3 of 12), these rates were lower than those in the carcinomatous components. Six patients died of their disease between 5 and 36 months after the diagnosis was made. The recognition of sarcomatoid carcinomas has important therapeutic and prognostic implications. It seems appropriate to treat these neoplasms in the same manner as conventional high-grade TCCs with similar degrees of invasion. We consider that sarcomatoid carcinomas should be regarded as a high-grade carcinoma that shows a prominent pseudosarcomatous dedifferentiation. The sarcomatoid component of sarcomatoid carcinomas may result from either anaplastic changes or dedifferentiation related to the process of losing cell adhesion molecules.

Short arm of chromosome 1 aberration recurrently found in pigmented villonodular synovitis

Pigmented villonodular synovitis (PVNS) is a relatively uncommon benign lesion that is characterized by diffuse synovial proliferation, mainly occurring in knee joints. Cytogenetic reports about this lesion are few and they describe the presence of numerical and structural chromosome aberrations. We obtained PVNS tissue from the left knee joint of a 53-year-old female, and performed cytogenetic analysis. Fluorescence in situ hybridization (FISH) was also performed by using the formalin fixed, paraffin embedded PVNS tissue. Two seemingly unrelated clones were found: the first clone had structural abnormalities of chromosome 1, 3, and 18, and the second one had trisomy 7 as a sole numerical abnormality. FISH using a chromosome 7 specific alpha-satellite DNA probe revealed that interphase nuclei possessed two or three signals. We describe the clonal aberrations found in a case of PVNS. The deleted lesion of the chromosome 1 (1p10-1p31.3) includes the locus of coagulation factor III gene (1p22-p21), and the coagulation factor V (1q21-q25) locus includes another breakpoint that is 1q25. In addition, recurrent structural abnormalities at the short arm of chromosome 1 have been reported. These facts might play some role in the hemorrhagic tendency and histogenesis of these lesions.

Malignant fibrous histiocytoma. A tumor of facultative histiocytes showing mesenchymal differentiation in cultured cell lines.

The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologio characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors, and immunophagocytosis. However, these cells differed from monocyte‐derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu‐M1 (CD15) and Leu‐M3 (CD14), which recognize the cells of the monocyte‐macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.

Ossifying fibromyxoid tumor of soft parts. Cytogenetic findings.

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown.

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

Cytogenetic analysis of Bednar tumor (pigmented dermatofibrosarcoma protuberans) has not been reported previously. Here, we report the identification of a supernumerary ring chromosome in a Bednar tumor by chromosome painting with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Chromosome painting with FISH demonstrated that the supernumerary ring chromosome was composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed by CGH. These results indicate that Bednar tumor and dermatofibrosarcoma protuberans are characterized by the same chromosomal features. To our knowledge, this is the first report that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22.

Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.

To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as “facultative histiocytes” with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (<2%), and S-100 protein (<1%). Our results indicate the presence of heterogeneity of “histiocytic” cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton- type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.

A case of lipoblastoma with t(3;8)(q12;q11.2)

We studied a single case of lipoblastoma in a 4-year-old boy. Cytogenetic analysis of the tumor cells showed two abnormal clones: 47,XY,t(3;8)(q12;q11.2),+mar, and 46,XY,t(3;8)(q12;q11.2). To our knowledge, this is the second report of chromosome findings in this rare tumor. Although lipoblastomas are frequently confused with myxoid liposarcomas, breakpoints in our patient were different from those of myxoid liposarcoma.

Tumoral calcium pyrophosphate dihydrate crystal deposition disease. A clinicopathologic analysis of five cases.

We describe five cases of tumoral calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) and discuss the clinical, radiological and pathological features. Patients included 4 males and 1 female, ranging in age from 49 to 70 years (median, 63 yrs). The wrist was involved in two patients. The thumb, palmar aspect of the proximal phalanx of the middle finger and dorsum of the carpal bone of the hand were involved in one patient each. In one patient, a preoperative diagnosis of chondrosarcoma had been made. Macroscopically, the lesion was a circumscribed whitish-gray mass with a more or less chalky appearance, measuring between 1.0 to 6.2 cm (median, 2.5 cm). Histologically, all five lesions contained areas of calcification with crystal deposits and chondroid metaplasia. The majority of crystals were rhomboid in shape, characteristic of CPPD, but some needle-shaped crystals were also identified, which resembled urate crystals. A review of the 54 reported cases of tumoral CPPDCD including our series indicated that they could be divided into two categories based on anatomic location: central (head and neck) type (n = 33) and distal (extremity) type (n = 21). Patients of these two groups were not different with respect to age and gender, but those with the central type often presented with a painful mass (15 patients, 46%), or neurological disturbances (11 patients, 33%). Patients with the distal type presented with a painless mass or swelling (12 patients, 57%), but none had neurological signs, although 8 (38.1%) presented with acute attack similar to tophaceous gout. Tumoral CP-PDCD should be differentiated from tophaceous gout, tumoral calcinosis, and malignant or benign tumors.

Epithelioid sarcoma with an 18q aberration.

Epithelioid sarcoma is a peculiar soft-tissue neoplasm of uncertain origin, which is characterized by an epithelioid morphology of tumor cells coexpressing epithelial (keratin) and nonepithelial (vimentin) antigens. We herein report a new cytogenetic abnormality with der(22)t(18;22)(q11;p11.2) in a case of epithelioid sarcoma that occurred in the elbow of a 75-year-old man. Histologically, the tumor demonstrated a multinodular proliferation of epithelioid cells, with positive immunostaining for keratin, epithelial membrane antigen (EMA), and vimentin. Cultured tumor cells obtained from fresh surgical materials were frozen in plastic ampules and stocked in a liquid nitrogen freezer. Six years after surgery, the cells were recovered from the freezer and utilized for both morphologic and cytogenetic analyses. These cultured cells both before and after the freezing exhibited essentially the same epithelioid morphology and immunophenotypes as those of the original tumor. A chromosome analysis, together with fluorescence in situ hybridization (FISH), demonstrated a 61-67 modal population, and a characteristic clonal abnormality with der(22)t(18;22)(q11;p11.2). Other clonal abnormalities included numerical (-3, -4, +7, -13, -14, -16, -18, +20, -22) and structural (8p+, 9p+, 12p+, i(21q)) aberrations. Some variant clones also demonstrated i(18q). Since the breakpoint at 18q11 is similar to that reported in synovial sarcoma, this finding may support the presence of a histogenetic relationship between epithelioid sarcoma and synovial sarcoma. Our study thus indicates that the storage of frozen cells is useful for both morphologic and cytogenetic analyses of soft tissue tumors.

Renal Primitive Neuroectodermal Tumor: A Morphologic, Cytogenetic, and Molecular Analysis with the Establishment of Two Cultured Cell Lines

We report two patients with renal primitive neuroectodermal tumor (PNET) in whom the diagnosis was established by both a cytogenetic and a molecular analysis. Histologically, both renal tumors were composed of uniform immature round cells with a positive immunoreactivity for 013 (p30/32 MIC2). The cytogenetic analysis with in situ hybridization (chromosome painting) demonstrated reciprocal translocation t(11;22)(q24;q12) specific to PNET in the cultured cells derived from each tumor. The reverse transcriptase-polymerase chain reaction (RT-PCR) in both tumors demonstrated EWS/ FLI-1 fusion transcripts, representing the molecular equivalent of t(11; 22). A Southern blot analysis also confirmed EWS gene rearrangement in both renal tumors. In addition, the authors also established two new cell lines (designated as FU-RPNT-1 and FU-RPNT-2) from renal PNETs. When transplanted into athymic mice, FU-RPNT-1 and FU-RPNT-2 reproduced and maintained the morphologic and molecular characteristics of the original tumors. In conclusion, the detection of t(11; 22) and EWS/FLI-1 fusion transcripts is considered to provide a novel adjunctive method for diagnosing renal PNET. These newly established cell lines thus may be used to investigate the biologic behavior related to renal PNETs.