Clear CelI HepatocelIular Caxinoma with Abundant Myxoid Stroma

A case of the clear cell variant of hepatocellular carcinoma with an abundant myxoid stroma is presented. The tumor occurred in a 55 year old Japanese man, and swelling of the scrotum was the initial symptom. The patient underwent high-level orchiectomy, and the pathologic diagnosis was a metastatic tumor on the surface of the processus vaginalis and intact testis. Extensive examination failed to show a primary site. Subsequent autopsy revealed a large hepatic tumor and metastatic nodules with a prominent myxoid appearance in multiple organs. Histological-ly, each tumor consisted of uniform small tumor cells with clear cytoplasm attributed to abundant accumulation of glycogen particles, and an abundant myxoid stroma was also present. The tumor cells were positive for keratin, α1– antitrypsin, α1-antichymotrypsin, liver ferritin, prealbumin, and fibrinogen, but lacked α fetoprotein. These findings indicated that this case was hepatocellular carcinoma of the clear cell type with a prominent myxoid stroma. Acta Pathol Jpn 42: 897–903, 1992.     

Myxoid variant of epithelioid leiomyosarcoma of the uterus.

A rare case of myxoid variant of epithelioid leiomyosarcoma of the uterus in a 76-year-old woman is reported. Palpation and computed tomography revealed an enlarged uterus. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and a hemispheric tumor, measuring 2.7 x 2.5 x 1.8 cm, was found protruding into the uterine cavity of the upper uterine segment. The tumor contained a prominent myxoid stroma and epithelioid tumor cells, which were round and polygonal in shape and showed positive immunoreactivity for desmin and vimentin. High mitotic activity was observed in the tumor cells. Electron microscopic examination revealed bundles of filaments in the cytoplasm and fine reticular material in the extracellular matrix. Histochemically, the myxoid stroma contained abundant acid mucopolysaccharide. The tumor cells were considered to originate from smooth muscle cells, while the myxoid stroma expressed varying differentiation of uterine mesenchymal cells. The patient is currently well with no evidence of recurrence or metastasis one year after the operation.     

Squamous cell carcinoma with prominent myxoid stroma

Three cases of a squamous cell carcinoma with a prominent myxoid stroma are reported. One case in a 70-year-old woman had presented as a lump in the breast, the other two presented as polypoid lesions of the larynx and cervix uteri in a 65-year-old man and 61-year-old woman, respectively. The carcinomatous component was immersed in abundant extracellular mucosubstances. In addition to occasional squamous pearls, it displayed immunocytochemical evidence of high-weight keratin present in the neoplastic cells and, in one case, desmosomal attachment under electron microscopy. The extracellular mucosubstances proved to be similar to those seen in connective tissue. The differential diagnosis with histologically similar lesions has been taken into consideration, and it has been suggested that this newly described entity showing abundant myxoid stroma has to be distinguished from numerous benign and malignant myxoid soft tissue tumors.     

Clear cell variant of fibrolamellar carcinoma of the liver

Fibrolamellar carcinoma of the liver is a distinctive variant of hepatocellular carcinoma characterized histologically by trabeculae of oncocytic cells with intervening lamellae of collagen fibers. We describe a case with a prominent component of clear cells, a feature not previously recognized in this tumor type. The patient was a 59-year-old woman incidentally found to have a solitary liver tumor, measuring 5 cm. Pathologic examination revealed a circumscribed, firm, tan tumor with peculiar concentric streaks. Oncocytic cells and clear cells were arranged in trabeculae separated by lamellae of collagen or sinusoids. The clear cells possessed abundant finely reticulated clear cytoplasm, which was highlighted by trichrome stain and immunostaining with antimitochondria antibody. Ultrastructurally, the cytoplasm of the clear cells was packed with empty membrane-bound vesicles that occasionally contained short cristae. The features suggested that the clear cell change resulted from ballooning and rarefactive changes of mitochondria. Clear cell fibrolamellar carcinoma should not be confused with conventional clear cell hepatocellular carcinoma, since the former is associated with a more favorable prognosis.     

Myxoid Variant of Epithelioid Leiomyosarcoma of the Uterus

A rare case of myxoid variant of epithelioid leiomyosarcoma of the uterus in a 76-year-old woman is reported. Palpation and computed tomography revealed an enlarged uterus. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and a hemispheric tumor, measuring 2.7 X 2.5 X 1.8 cm, was found protruding into the uterine cavity of the upper uterine segment. The tumor contained a prominent myxoid stroma and epithelioid tumor cells, which were round and polygonal in shape and showed positive immunoreactivity for desmin and vimentin. High mitotic activity was observed in the tumor cells. Electron microscopic examination revealed bundles of filaments in the cytoplasm and fine reticular material in the extracellular matrix. Histochemically, the myxoid stroma contained abundant acid mucopolysaccharide. The tumor cells were considered to originate from smooth muscle cells, while the myxoid stroma expressed varying differentiation of uterine mesenchymal cells. The patient is currently well with no evidence of recurrence or metastasis one year after the operation. Acta Pathol Jpn 41: 778-783, 1991.     

Malignant melanoma with a myxoid stroma: a diagnostic pitfall on fine-needle aspiration biopsy

Malignant melanoma (MM), both primary and metastatic, may be associated with a prominent myxoid stromal reaction causing diagnostic confusion on fine-needle aspiration biopsy (FNAB), most often with sarcomas that demonstrate a myxoid stroma, particularly malignant peripheral nerve sheath tumor (MPNST). We present a case of a 32-yr-old man with no past medical history who presented with a unilateral neck mass clinically suspicious for lymphoma. FNAB produced a specimen composed of large sheets of anaplastic cells encased in a myxoid stroma that was S100 and vimentin-positive but HMB-45-negative. A diagnosis of MPNST was made. Excision demonstrated a metastatic MM of unknown primary, with a prominent myxoid stromal reaction. A repeat HMB-45 was again negative. Electron microscopy demonstrated intracytoplasmic melanasomes and cisternae of rough endoplasmic reticulum with intracisternal parallel tubules, confirming the diagnosis. Although HMB-45 is typically negative in both tumors, S100 should be strongly positive in myxoid MM and only focal in MPNST.     

Clear cell renal cell carcinoma with smooth muscle stroma

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.     

Dendritic fibromyxolipoma: A variant of spindle cell lipoma with extensive myxoid change,with cytogenetic evidence

Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67‐year‐old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed.     

Inflammatory myofibroblastic tumor of the uterus with prominent myxoid change

A surgical case of inflammatory myofibroblastic tumor arising in the uterine corpus and exhibiting prominent myxoid change of the stroma is reported. The patient was a 63-year-old woman with a large tumor mass that filled the uterine cavity and measured 11 cm in maximal dimension. The tumor had a gelatinous appearance and consisted of a loose proliferation of stellate or polygonal cells on a myxomatous background. Fascicular proliferation of spindle cells was also observed focally, and a chronic inflammatory cell infiltration was seen in many areas. Tumor cells had mild atypism and were immunoreactive for vimentin, alpha-smooth muscle actin, and anaplastic lymphoma kinase (ALK). Focal immunoreactivity for high-molecular-weight caldesmon (h-caldesmon) was also noted. The patient has been free from recurrence for 8 months. Inflammatory myofibroblastic tumor of the uterus occasionally shows prominent myxoid change of the stroma, and differentiation from myxoid leiomyosarcoma is problematic in these cases. Based on the immunoreactivity of tumor cells for ALK and h-caldesmon, the present tumor was considered inflammatory myofibroblastic tumor showing a focal phenotypic transition from myofibroblasts to smooth muscle cells.     

Metastatic hepatocellular carcinoma of skin diagnosed with hepatocyte paraffin 1 and a-fetoprotein immunostainings

A rare case of skin metastasis of hepatocellular carcinoma diagnosed with an aid of immunohistochemical stainings of hepatocyte paraffin 1 and a-fetoprotein is reported in this study. An 86-year-old Japanese man was admitted to our hospital due to cutaneous mass in the right chest. An incisional biopsy was performed, which showed proliferation of malignant cells with eosinophilic or clear cytoplasm arranged in solid nests. No trabecular pattern was recognized. Sebaceous carcinoma, clear cell sarcoma, malignant granular cell tumor, metastatic renal cell carcinoma, and metastatic hepatocellular carcinoma were suspected on hematoxylin and eosin preparations. An immunohistochemical study showed that the tumor cells were positive for cytokeratins, hepatocyte paraffin 1, and a-fetoprotein but negative for vimentin, desmin, a-smooth muscle actin, S-100 protein, epithelial membrane antigen, carcinoembryonic antigen, chromogranin, neuron-specific enolase, CD10, CD30, CD34, CD45, CD68, and HMB45. Metastatic hepatocellular carcinoma of the skin was diagnosed pathologically. This case suggests that skin tumors with eosinophilic cytoplasm should be examined by hepatocyte paraffin 1 and a-fetoprotein.     

Peritoneal washing cytology findings of disseminated myxoid leiomyosarcoma of uterus: report of a case with emphasis on possible differential diagnosis

We report the cytology findings of a rare case of myxoid leiomyosarcoma of the uterus with intraabdominal dissemination. The cytology showed uniformly dispersed spindly to polygonal "epithelioid" tumor cells focally linked by background matrix. Spindly tumor cells attaching to and radiating from branching capillary structures were also present. Occasionally, scattered "signet-ring" cells were found, mimicking metastatic poorly differentiated adenocarcinoma. The background mucoid substance was more conspicuous in the cell block sections. Gross and histologic examination of the surgical specimen revealed a large uterine leiomyosarcoma with prominent myxoid change. Ultrastructural study showed that the "signet-ring" appearance was mainly due to degenerative cytoplasmic change with ballooning of mitochondria, dilatation of endoplasmic reticulum, and elevation of outer nuclear membrane. In contrast to other spindle cell malignancies such as sarcomatoid mesothelioma, sarcomatoid carcinoma, or malignant melanoma, true sarcoma cells in general carry a distinctive cytologic appearance in washing/effusion fluid. In a correct clinical setting, the peculiar association with mucoid matrix and absence of classic lipoblasts should also raise the suspicion of metastatic myxoid leiomyosarcoma.     

Papillary carcinoma with nodular fasciitis-like stroma--a case report in pregnancy

We report a case of Papillary carcinoma with nodular fasciitis-like stroma that is a rare variant of Papillary carcinoma characterized by a prominent stromal cell proliferation that causes difficulties in cytologic and histologic diagnosis. The patient was a 34-year-old woman, pregnant, presented with a 1-year history of a growing mass in neck, dysphagia, and hoarseness. Physical examination revealed a firm nodular mass in thyroid gland. The fine needle aspiration biopsy specimen contained, besides diagnostic epithelial features of Papillary thyroid carcinoma, discohesive arrangement of bland spindle cells. Macroscopically, the specimen consisted of nodular tumor measuring 10 x 6 x 6 cm. Histologically the tumor was composed of small foci of neoplastic epithelial component distributed in abundant stroma. In immunohistochemistry, spindle cells in the stroma were positive for alpha-smooth muscle actin and the neoplastic cells showed positive staining for TTF-1 and progesterone receptor.     

Intracranial chondromyxoid fibroma extending into the jugular foramen

A case is reported of an intracranial chondromyxoid fibroma (CMF) in a 67 year old man. The tumor originated in the petrous part of the temporal bone and extended into the jugular foramen. Microscopically, the tumor showed a lobular appearance, and was composed of spindle or stellate cells in an abundant myxoid, chondroid stroma. Immunohistochemically, S-100 protein was positive in the tumor cells and myxoid stroma. Intracranial CMF, especially in an elderly person, is exceedingly rare. Clinical and pathological findings are presented with reference to the previously reported articles.     

Participation of liver cancer stem/progenitor cells in tumorigenesis of scirrhous hepatocellular carcinoma--human and cell culture study

Cancer stem cells reportedly participate in the tumorigenesis of some neoplasms. Scirrhous hepatocellular carcinoma is a variant of hepatocellular carcinoma with abundant fibrous stroma. Herein, we clinicopathologically examined scirrhous (29 cases) and conventional (50 cases) hepatocellular carcinoma with reference to cancer stem cells. Scirrhous hepatocellular carcinoma was classifiable into 3 types based on small neoplastic cells at the periphery of tumor cell nests. Of 29 cases of scirrhous hepatocellular carcinoma, 21 contained small neoplastic cells. Immunohistochemically, those cells were positive for cytokeratin 7 and ATP-binding cassette transporter G2. In 11 cases, those small tumor cells were also positive for cytokeratin 19, neural cell adhesion molecule, and epithelial cell adhesion molecule (type 1), whereas 10 cases did not show such additional expression (type 2). The remaining 8 tumors did not contain small tumor cells with stem cell features (type 3). In the central parts of tumor nests, carcinoma cells got hepatocellular markers and lost expression of neural cell adhesion molecule, and epithelial cell adhesion molecule, suggesting hepatocellular maturation. Transforming growth factor beta1, a fibrogenic cytokine, was also detected in those small tumor cells. Culture cells extracted as "side population" from hepatocellular carcinoma cell lines (HuH7 and PLC5) expressed more intensely cytokeratins 7 and 19, neural cell adhesion molecule, epithelial cell adhesion molecule, and transforming growth factor beta1 than did non-side population cells. Small tumor cells with stem cell features in scirrhous hepatocellular carcinoma may correspond to side population of culture cells and might be involved in fibrogenesis of scirrhous hepatocellular carcinoma.     

Epithelial marker-negative desmoplastic small round cell tumor with atypical morphology: definitive classification by fluorescence in situ hybridization

Desmoplastic small round cell tumor typically presents with abundant desmoplastic stroma containing nested primitive round cells bearing a polyphenotypic immunohistochemical profile. Lesions with minimal classic morphology pose a formidable diagnostic challenge. The current case represents one such example, arising as a large abdominal-pelvic mass in a 17-year-old female patient. The tumor was composed of a monomorphous population of small round cells lining microcystic structures and forming pseudoacini and fine anastomosing trabeculae and cords. The stroma was abundantly myxoid with only occasional thick desmoplastic septa. The tumor cells were variably immunopositive for vimentin, desmin, smooth muscle actin, synaptophysin, neuron-specific enolase, Bcl-2 and WT1 (nuclear); epithelial markers were negative. The definitive diagnosis of desmoplastic small round cell tumor was rendered with the demonstration of the characteristic EWS-WT1 gene fusion by fluorescence in situ hybridization. The current case emphasizes the utility of fluorescence in situ hybridization to demonstrate EWS-WT1 gene fusion in desmoplastic small round cell tumor with nonclassic morphologic and immunohistochemical features to avoid potential misdiagnosis.     

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.     

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 6 x 4 x 4 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.     

Rare renal tumor--mucinous tubular and spindle cell carcinoma

We report a rare case of renal tumor--mucinous tubular and spindle cell carcinoma in a 65-year-old man. The tumor, located in the right kidney, was well circumscribed. Microscopically, the tumoral proliferation was composed of cuboidal cells arranged in tubules, with abrupt transition to spindle cell morphology in a myxoid stroma. Because of the favorable prognosis with this type of tumor, mucinous tubular and spindle cell carcinoma must be differentiated from papillary renal cell carcinoma, especially the variant with sarcomatoid dedifferentiation.     

Myxoid melanoma of the skin

We report a case of cutaneous myxoid melanoma in a 61-year-old man. Histologically, the tumor, which showed an adjacent intraepidermal proliferation of atypical melanocytes, was composed of spindle-shaped and epithelioid cells with atypical nuclei, arranged in lobules and embedded in a prominent myxoid stroma. Primary cutaneous myxoid melanoma is rare: we found only one other example in the literature.