Biomedical subjects

Masaharu Fukunaga

Publications and source records attributed to Masaharu Fukunaga.

At least 19 recordsLinked to original sources

PubMed2006

Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens.

A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

Adolescent↗

PubMed2006

Hepatoid carcinoma with serous component of the fallopian tube: a case report with immunohistochemical and ultrastructural studies.

A very rare case of hepatoid carcinoma with serous component arising in the fallopian tube of a 79-year-old woman is presented. The lesion was a 5.0-cm unencapsulated, yellowish-white soft mass. The tumor was composed of hepatoid carcinoma (90%) and serous carcinoma (10%) components. The hepatoid carcinoma was histologically characterized by a proliferation of round to polygonal cells arranged in a trabecular, tubular, sinusoidal, papillary, or solid pattern. The serous component in the fallopian tube also showed in situ lesions. Both components showed an infiltration into the surface of the left ovary, omentum, peritoneum including the pouch of the Douglas, and serosa of the colon. Immunohistochemically, the hepatoid carcinoma was positive for alpha-fetoprotein, polyclonal carcinoembryonic antigen (CEA), hepatocyte paraffin 1, albumin, epithelial membrane antigen, and cytokeratin (CAM5.2). Ultrastructurally, the cytoplasm contained abundant ribosomes, moderate amounts of mitochondria, and rough endoplasmic reticulum that developed into a meshwork and contained mitochondria within it. Microbile channel-like structures and desmosomes were occasionally observed. The association with serous carcinoma indicates mullerian origin rather than germ cell origin. The patient received chemotherapy and was alive without disease at 10 months after surgery.

Aged↗

PubMed2006

Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma.

BACKGROUND: Recent investigations have demonstrated the utility of the monoclonal antibody D2-40 as a marker for lymphatic endothelium. D2-40 can be used on formalin-fixed and paraffin-embedded materials. Our objective was to elucidate, using D2-40 immunohistochemistry, the differences among capillary hemangiomas, and especially between kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). We studied four cases of KHE, nine cases of TA, and 31 cases of other vascular tumors. Antibodies against CD31, CD34, factor VIII-related antigen, and GLUT1 were also applied. RESULTS: In KHE, D2-40 was markedly reactive for three and partially for one of four cases in the peripheral area of Kaposi's sarcoma-like proliferative capillaries and negative in the surrounding dilated vessels. In TA, D2-40 was partially positive in the surrounding dilated vessels and negative in cannonball-like proliferative capillaries. CONCLUSIONS: Our results suggest that D2-40 is a useful antibody for immunohistochemical discrimination between KHE and TA. In addition, the difference of immunostaining pattern of D2-40 is limited to the peripheral area of capillary proliferation and surrounding dilated vessels; therefore, it is suggested that KHE and TA may reflect different stages in the evolution of a single entity. Namely, they may originate from stem cells possessing the characteristics of both lymphatic and blood vessel endothelial lineages.

Antibodies, Monoclonal↗

PubMed2005

Low-grade central osteosarcoma of the skull.

A case of low-grade central osteosarcoma of the skull in a 36-year-old male is described. A 10cm mass of the left temporo-occipital bone, which was incidentally found 6 years previously on the occasion of a head trauma, was osteolytic and osteoplastic, affecting soft tissues and the subdural space. The patient was treated with intralesional curettage. Histologically, the tumor was characterized by spindle cell proliferation with woven and lamellar bone formation, resembling fibrous dysplasia, parosteal osteosarcoma, low-grade fibrosarcoma, or desmoplastic fibroma. The spindle cells were fairly uniform with mild atypia and low-mitotic activity (3 per 50 high power fields), and cellularity varied from low to high. Clinicians and pathologists should be aware of this type of low-grade osteosarcoma of the skull and distinguish it from its mimics, including fibrous dysplasia, parosteal osteosarcoma, and low-grade fibrosarcoma. Careful microscopic correlation with radiographic findings is the clue to the correct diagnosis.

Adult↗

PubMed2005

Cutaneous spindle cell carcinoma following basal cell carcinoma.

A spindle cell carcinoma arose three years after the seeming excision of a so-called "infiltrative" basal cell carcinoma (IBCC) in the cheek of an 87-year-old Japanese woman. The patent had no history of irradiation. The tumor was composed of short fascicles and whorling arrangements of spindle to polygonal cells without residual IBCC. Immunohistochemically, the tumor was positive for vimentin, cytokeratin 8 & 18, epithelial membrane antigen, and alpha-smooth muscle actin. Ultrastructurally, the tumor cells had tonofilaments and desmosomes. The patient died after a local recurrence with metastatic lesions in the lung and the neck lymph nodes that were indicated by CT scanning and MRI at nine months after diagnosis. This case and others support the concept that spindle cell carcinoma can pursue an aggressive clinical course.

Actins↗

PubMed2005

Interobserver and intraobserver variability in the diagnosis of hydatidiform mole.

Surgical pathologists often encounter hydropic villi in products of conception at the first trimester and must determine whether the villi represent complete hydatidiform mole (CM), partial hydatidiform mole (PM), or hydropic abortion (HA). The distinction between these is important for determining the appropriate treatment of patients. This study assessed interobserver and intraobserver variability in the histologic diagnosis of hydatidiform mole among 5 placental pathologists. To evaluate interobserver variability, one representative slide from each of 50 mixed cases of PM, CM, and HA of the first trimester were circulated among 5 placental pathologists. All pathologists used the same histologic criteria by Szulman and Surti. For the second round, the same cases were submitted with DNA ploidy data. For the third round, the slides were recoded and distributed to assess intraobserver agreement. Kappa (kappa) value was calculated for the interobserver agreement in the first and second rounds. There was agreement among 4 or 5 pathologists for only 30 of 50 cases in the first round. There were problems in differentiating between PM and HA in most of the remaining 20 cases. The kappa values varied from poor (kappa = -0.104) to excellent (kappa = 0.761) in the first round. In the second round, there was agreement in 39 of 50 cases and the level of agreement remarkably increased, ranging from fair to good (kappa = 0.552) to excellent (kappa = 0.851). The number of discrepant cases, PM versus HA, was reduced to 4. In 7 cases, there were difficulties in distinguishing CM from HA. The intraobserver agreement ranged from 50% to 90%. Poor interobserver agreement was demonstrated when histology alone was used for diagnosis. Discordance was most frequently seen in PM versus HA and resulted from difficulty in evaluating trophoblastic hyperplasia. Polar trophoblastic growth seen in HA could also be observed in PM. The addition of ploidy data resulted in a significant improvement in concordance. Ploidy study is useful in equivocal cases. Significant interobserver and intraobserver variability was observed even among placental pathologists. New histologic criteria adaptable to differentiation of early lesions are needed.

Abortion, Spontaneous↗

PubMed2005

Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast.

We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.

Adenocarcinoma, Mucinous↗

PubMed2005

Perivascular epithelioid cell tumor of the uterus: report of four cases.

Uterine perivascular epithelioid cell tumor (PEComa) is very rare, and there have been only 27 reported cases. The differentiation of the tumor has been enigmatic, and the biologic behavior remains unclear. This study describes the clinical, histologic, and immunohistochemical features of four cases of uterine PEComa. The patients were 30, 32, 36, and 40 years old, and none of them had tuberous sclerosis complex. The size of the tumors ranged from 1 to 30 cm in diameter, and 3 of the 4 tumors were confined in the uterus. One tumor involved the left ovary and omentum. Microscopically, the tumors were characterized by an epithelioid arrangement of tumor cells, which had abundant clear to eosinophilic pale granular cytoplasm, and one tumor had moderately atypical nuclei. Coagulative necrosis was found in two cases. The mitotic figures ranged from 0 to 11 per 10 high power fields. Immunohistochemically, the tumors were positive for vimentin (4/4), HMB45 (4/4), h-caldesmon (4/4), alpha-smooth muscle actin (3/4), muscle actin (2/4), and desmin (3/4). They were uniformly negative for Melan A, CD10, and S-100 protein. Ultrastructural examinations were performed on one case and revealed no melanosomes, premelanosomes, or evidence of smooth muscle differentiation. One patient died of intestinal metastases 17 months after surgery. The other patients have been well with no evidence of disease 8, 12, and 36 months after surgery. Uterine PEComa should be regarded as tumors with an uncertain malignant potential until long-term outcome data for a larger number of patients become available.

Actins↗

PubMed2005

Osteogenic melanoma.

A case of osteogenic melanoma arising in the sole of the foot of a 75-year-old male is described. The patient had a history of cutaneous malignant melanoma of the left sole from 15 years previously with local recurrence 5 years previously. A second recurrence presented as an unencapsulated, poorly circumscribed mass measuring 7.5x6x3 cm, located in the dermis, subcutis and muscle, and composed of a lobular growth of malignant osteocartilaginous elements with foci of epithelioid cells. The tumor was strongly positive for HMB45 and S-100 protein. No conventional melanoma was found in the skin. The patient had no evidence of recurrence or metastasis 10 months after surgery. Pathologists and clinicians should be aware of the existence of osteogenic melanoma and should differentiate it from mimics.

Aged↗

PubMed2005

Juvenile temporal arteritis associated with Kimura's disease.

A case of juvenile temporal arteritis, which is a rare vascular lesion in children and young adults, associated with Kimura's disease in a healthy 23-year-old asymptomatic man is described. The patient presented with a painless 2.5 cm nodule with eosinophilia and normal erythrocyte sedimentation rate. Histologically, the left superficial artery showed marked intimal thickening with moderate eosinophilic infiltrates, constriction of the vascular lumen, focal disruptions of the internal elastic lamina and media, moderate eosinophilic infiltrates in the adventia, and absence of giant cells. The subcutaneous tissue surrounding the artery was characterized by lymphofollicular hyperplasia, marked eosinophilic infiltrates in the intra- and extra-follicles with abscess, capillary proliferations, lymphocytic, plasma cell and mast cell infiltrates, and fibrosis in the interfollicular region. Immunohistochemically, reticular, positive IgE staining was observed in the germinal centers. Clinically and histologically, the lesion was consistent with juvenile temporal arteritis associated with Kimura's disease. The findings indicate that both entities are closely related and juvenile temporal arteritis may be secondary to Kimura's disease.

Adult↗

PubMed2004

Epithelioid variant of pleomorphic liposarcoma: report of a case.

A case of an epithelioid variant of pleomorphic liposarcoma (PL) arising in the back of a 72-year old male is presented. The lesion was a well-circumscribed but unencapsulated, yellowish white mass measuring 11 x 10 x 9 cm in the subcutis and muscle. Histologically, the tumor consisted of three elements; an epithelioid cell element occupying about 50%, a lipogenic and mixed lipogenic and epithelioid cell element occupying 40%, and a malignant fibrous histiocytoma-like element. The lipogenic area was composed of uni- and multivacuolated pleomorphic lipoblasts. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and CD10. It was negative for desmin, alpha-smooth muscle actin, muscle actin, S-100 protein, and cytokeratins 8 and 18. The epithelioid variant of PL should be differentiated from metastatic renal cell carcinoma and adrenal cortical adenocarcinoma.

Aged↗

PubMed2004

Endometrioid carcinoma of the fallopian tube resembling a female adnexal tumor of probable wolffian origin.

Endometrioid carcinoma of the fallopian tube resembling a female adnexal tumor of probable wolffian origin (FATWO) is a rare, recently delineated, low-grade carcinoma that may be confused with both FATWO and high-grade carcinoma. Only about 20 cases have been reported so far, but it probably represents almost half of the endometrioid carcinomas of the fallopian tube. It has a better prognosis than conventional tubal endometrioid and serous carcinomas. Macroscopically, the tumors form a small, solid, polypoid mass that is usually confined within the tube. Microscopically, the tumors are characterized by proliferations of spindle cells in whorls and closely packed confluent elongated glands with focal tubular, sieve-like, and papillary structures. Unlike FATWO, this variant of endometrioid carcinoma exhibits focal squamous differentiation, intraluminal mucin, mild to moderate nuclear atypia, and occasional mitosis. Unlike FATWO, tumor cells are negative for inhibin-alpha and calretinin.

Carcinoma, Endometrioid↗

PubMed2004

Immunohistochemical characterization of cyclin E and p27KIP1 expression in early hydatidiform moles.

The aim of this study is to evaluate whether the expression of p27 (p27) and cyclin E (cE) is related to the development of hydatidiform moles and whether their expressions are associated with prognosis in these lesions. Ten diploid voluntary artificial abortions (ABs), 20 diploid hydropic abortions (HAs), 20 triploid partial moles (PMs), and 44 diploid complete moles (CMs) (including 4 with persistent disease), all of which were in the first trimester, were evaluated by immunohistochemistry of formalin-fixed tissues using monoclonal antibodies against p27 and cE protein. DNA ploidy in all cases was analyzed by flow cytometry. In ABs, nuclear cE was expressed at low (1+) to moderate (2+) levels in cytotrophoblast (CT), intermediate trophoblast (IT) and occasionally in syncytiotrophoblast (ST). In all CMs, cE-positive nuclei of CT were observed at high levels (3+), and (1+) to (2+) levels in clusters of IT. On the other hand, all HAs and PMs showed cE levels comparable to those observed in ABs. There was a significant difference in cyclin E expression in CT between CMs and non CMs, but there was no significant difference of cE levels between CMs with and without persistent disease. In 3 of 10 ABs, nuclear p27 was expressed at (1+) levels in ST. Similar expression was observed in 27 (including 2 invasive lesions) of 44 CMs, 10 of 20 PMs, and 8 of 20 HAs. CT and IT were rarely positive (1+) for p27 in the cases examined. Decidual stromal cells provided a reliable positive internal control for p27 expression. These findings support the hypothesis that trophoblast proliferation is related to the balance between the positive cell cycle factors, such as cE, and the negative cell cycle inhibitors, such as p27. The overexpression of cE in the trophoblastic elements suggests that cE protein expression may be dysregulated in early CMs. Neither cE nor p27 expression is a prognostic indicator in CMs.

Adolescent↗

PubMed2004

Perivascular epithelioid cell tumor of the uterus: a case report.

A case of perivascular epithelioid cell tumor (PEComa) arising in the subserosa of the uterus of a 32-year old woman is presented. The lesion, removed by local excision, was an unencapsulated rubbery mass 5.0 cm in diameter. The tumor was composed of round to polygonal cells with round nuclei and abundant clear to slightly eosinophilic cytoplasm containing glycogen, and the cells were arranged in short fascicles focally in a perivascular location. There were scattered foci of necrosis and hemorrhage. The tumor cells showed mild atypia and low mitotic activity, and they were strongly immunoreactive for vimentin, h-caldesmon, and HMB45. Ultrastructural examination showed no melanosomes or premelanosomes. The patient had no evidence of disease 8 months postoperatively. Uterine PEComas should be regarded as tumors with an uncertain malignant potential.

Adult↗

PubMed2004

Palisading subcutaneous fibrous histiocytoma.

A case of palisading subcutaneous fibrous histiocytoma, a very rare variant of fibrous histiocytoma (dermatofibroma), arising in the wrist of a 41-year-old man is presented. An unencapsulated subcutaneous tumor measuring 0.8 x 0.8 x 0.7 cm was histologically characterized by predominant nuclear palisading and a peripheral area with a pattern quite characteristic of conventional fibrous histiocytoma. Immunohistochemically, the tumor cells were strongly positive for vimentin, alpha-smooth muscle, and muscle actin, but negative for S-100 protein, indicating a fibroblastic or myofibroblastic nature. The patient has been well without recurrence for 6 years and 8 months after the excision. This neoplasm should be differentiated from benign and malignant skin or soft tissue tumors with a palisading pattern. Pathologists and clinicians should know of the existence of this type of fibrous histiocytoma and should avoid overdiagnosis and overtreatment.

Adult↗

PubMed2004

Tumor-like cystic endosalpingiosis of the uterus with florid epithelial proliferation. A case report.

Mass-like cystic endosalpingiosis is very rare. The author reports such a lesion with histologic features of endosalpingiosis of the uterus with florid epithelial proliferation in a 51-year-old female who complained of lower abdominal pain. Preoperatively, it was considered to be left-sided ovarian cancer. Intraoperatively, a subserosal, sessile polypoid mass with multiple cysts in the uterine fundus measuring 12 x 6.5 x 5.5 cm was found. Histologically, it was composed of multiple cysts lined by benign-appearing tubal epithelium and bland smooth muscular and myofibromatous stroma. Part of the epithelium exhibited marked papillarity and tufting. Features of conventional endometriosis were present focally. Pathologists and clinicians should be aware of the existence of this type of non-neoplastic lesion, mass-like cystic endosalpingiosis, and should avoid overdiagnosis and overtreatment.

Cysts↗

PubMed2004

Perivascular epithelioid cell tumor (PEComa) of soft tissue: case report with ultrastructural study.

A perivascular epithelioid cell tumor (PEComa) arising in the abdominal wall of a 44-year-old female is described. The lesion was a well-circumscribed but unencapsulated, rubbery, subcutaneous mass measuring 3.5 x 3.5 x 3.0 cm which was removed by simple excision. It was characterized by a nest- or sheet-like arrangement of round to polygonal cells with round nuclei and abundant clear to slightly eosinophilic cytoplasm containing glycogen. There was mild to moderate nuclear pleomorphism with mitotic activity of 6 per 10 high power fields. A short fascicular proliferation of the tumor cells was observed focally. The stroma contained abundant small vascular channels with hyalinization. Immunohistochemically, the tumor cells were strongly positive for vimentin, epithelial membrane antigen, alpha-smooth muscle actin, and HMB45. Ultrastructural examination showed poorly differentiated mesenchymal tumor cells without premelanosomes. There was local recurrence 6 years after excision. Pathologists and clinicians should be aware of the existence of PEComa in soft tissue and should differentiate it from other similar lesions.

Actins↗

PubMed2004

Neuron-specific enolase-producing leiomyosarcoma of the mesentery.

A case of neuron-specific enolase (NSE)-producing leiomyosarcoma arising in the mesentery of a 62-year-old female is presented. Preoperatively, serum level of NSE was markedly elevated. A well-defined but unencapsulated tumor measuring 14 x 12 x 9 cm was histologically characterized by a fascicular or herring-bone arrangement of atypical spindle or oval tumor cells with vesicular cigar-shaped nuclei, inconspicuous nucleoli and abundant clear to brightly eosinophilic cytoplasm. Immunohistochemically, the tumor was positive for vimentin, alpha-smooth muscle actin, muscle actin, desmin, and gamma-NSE. Postoperatively, serum level of NSE decreased to within normal range. The NSE levels were, however, elevated again as metastatic lesions in the liver had enlarged. The patient died of the liver metastases 10 months after surgery. Serum NSE level can be a useful index of tumor extent and for monitoring treatment of some patients with leiomyosarcoma.

Fatal Outcome↗