Masaharu Fukunaga

Ovarian atypical endometriosis: its close association with malignant epithelial tumours

The incidence of ovarian atypical endometriosis and its association with malignant epithelial tumours in a consecutive series of cases during the period 1987 to 1995 were studied. Atypical glandular changes were observed in four (1.7%) of 255 ovarian endometriosis cases and one patient with ovarian atypical endometriosis developed subsequent endometrioid carcinoma in the abdominal wall. Fifty‐four (24.1%) of the 224 ovarian cancers were associated with ovarian endometriosis; 21 with typical and 33 with atypical endometriosis. Clear cell carcinomas and endometrioid carcinomas were most frequently associated with endometriosis, with 54% (27 of 50 cases) and 41.9% (13 of 31), respectively. Atypical endometriosis was found in 18 clear cell carcinomas, in seven endometrioid carcinomas, in four serous carcinomas, in three mucinous borderline tumours, and in one serous borderline tumour. In 13 cases, the atypical endometriosis was in contiguity with malignant epithelial tumours. We consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with clear cell and endometrioid carcinomas. Close screening of cellular atypia or hyperplasia in ovarian endometriosis and careful long‐term follow‐up of patients with atypical endometriosis is required.

Expression of D2‐40 in lymphatic endothelium of normal tissues and in vascular tumours

Aims : To evaluate the expression of D2‐40 in normal lymphatic endothelium and vascular tumours or tumour‐like lesions of the skin and soft tissue. D2‐40 is a novel monoclonal antibody to a Mr 40 000 O‐linked sialoglycoprotein that reacts with a fixation‐resistant epitope in lymphatic endothelium.

Multicenter Phase II Study of Fertility-Sparing Treatment With Medroxyprogesterone Acetate for Endometrial Carcinoma and Atypical Hyperplasia in Young Women

PURPOSE To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women. PATIENTS AND METHODS This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points. RESULTS CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months. CONCLUSION The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.

Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome.

Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical hyperplasia (AH) of the endometrium who received conservative treatment to preserve fertility were collected from member institutions of the Japan Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed with EA without myometrial invasion and AH, respectively. We performed a central pathological review to make definite diagnoses, and the diagnosis of EA in 29 cases was changed to AH in ten, complex hyperplasia in three and atypical polypoid adenomyoma in three, and AH in ten was changed to EA in one and simple hyperplasia in one. Nine of 12 women (75%) with EA and 15 of 18 women (83%) with AH had an initial response to medroxyprogesterone acetate (MPA) treatment. Two of nine responders with EA later developed relapse, and one of them had metastasis to the left obturator lymph node. Two became pregnant, and one delivered one full-term infant. One of the responders with AH had a relapse in the endometrium. Five became pregnant, and four delivered four normal infants. The young women with endometrial carcinoma localized in the endometrium who wish to preserve fertility may be treated as successfully with MPA as those with AH.

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.

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 (κ) 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 κ values varied from poor (κ = −0.104) to excellent (κ = 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 (κ = 0.552) to excellent (κ = 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.

Atypical and malignant variants of ossifying fibromyxoid tumor. Clinicopathologic analysis of six cases.

Ossifying sibromyxoid tumor (OFMT) of soft parts is a recently defined fibro-osseous neoplasm. the biologic behavior of which is generally regarded as benign. We report six variant cases of OFMT with histologic features of malignancy, two of which behaved aggressively. All these tumors arose in the extremities of adults (aged 36–76 years), and five of the six were subcutaneous. Four patients were men. Macroscopically, all the tumors were well circumscribed and somewhat lobulated. Cardinal morphologic features included lobulates of round to spinded cells within a fibromyxoid matrix and randomly distributed, often centrally located osteoid within which were plump neoplastic cells. In contrast to typical OFMT, a hypocellular, cytologically benign, lamellar bony shell was observed only focally: cellularity was increased (four cases), and mitotic activity was frequent, exceeding two mitotic figures per 10 high-power fields (three cases). One case associated with metastases was morphologically bland. Immunohistochemically, positivity for S-100 protein was observed in the primary tumors of three cases and in the pulmonary metastasis of a fourth. Desmin was positive in one case. Ultrastructural features in three cases were very similar to usual OFMT. Clinical follow-up revealed local recurrence in two cases: one patient has developed recurrent pulmonary metastases. We believe these findings support the view that some atypical cases of OFMT exhibit morphologic patterns that might predict more aggressive behavior.

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.

Malignant solitary fibrous tumour of the peritoneum

Solitary fibrous tumour, formerly known as localized fibrous mesothelioma, may arise from the peritoneum in rare instances, whereas it commonly appears as a pleural neoplasm [1,2]. Solitary fibrous tumour of the peritoneum occurs in both sexes and in all age groups, but predominantly affects those between the 4th and 7th decades of life [1,2]. Unlike diffuse mesotheliomas, solitary fibrous tumour shows no relationship to asbestos exposure [1]. It tends to be asymptomatic or produces minor symptoms such as vague abdominal complaints [1]. Benign and malignant forms of the tumour occur, the benign variant being three to four times more common than the malignant. Solitary fibrous tumour of the peritoneum can be identified as a large mass [1,2], and needs to be distinguished from gynaecological tumours on imaging studies. We report here a case of malignant solitary fibrous tumour of the peritoneum. Computed tomography (CT) and magnetic resonance (MR) imaging findings are described.

Smooth muscle metaplasia in ovarian endometriosis.

Little is known about smooth muscle metaplasia (SMM) in ovarian endometriosis. The clinicopathological significance of SMM in ovarian endometriosis is analysed.