Cervical embryonal rhabdomyosarcoma and ovarian Sertoli-Leydig cell tumour: a more than coincidental association of two rare neoplasms?

A case in which an embryonal rhabdomyosarcoma of the cervix and an ovarian Sertoli-Leydig cell tumour of intermediate differentiation occurred in a 13-year-old girl is described. Although initially considered as a chance association, a review of the literature showed the co-occurrence of these two uncommon neoplasms in three previous cases. The reason for this association, which is thought to be more than coincidental, is not known, although an underlying genetic abnormality is a possibility. The ovarian tumour in this case was characterised by the presence of foci of cells with extremely pleomorphic nuclei, which initially raised the possibility of metastatic rhabdomyosarcoma. These were interpreted as foci of bizarre nuclei within the Sertoli-Leydig cell tumour.     

Bilateral retiform Sertoli-Leydig cell tumour in a bitch. Alpha-inhibin and epithelial membrane antigen as useful tools for differential diagnosis

Sertoli-Leydig cell tumours with a retiform pattern similar to the pattern of the rete testis are a subtype of sex cord-stromal tumours recognized in the human WHO histological classification of ovarian tumours but not in the equivalent classification for domestic animals. The morphology of the tumour may be confused with that of the more common ovarian epithelial tumours. The gross, microscopical and immunohistochemical features of a canine retiform Sertoli-Leydig cell tumour and its comparison with the human counterpart are presented in this report. Both ovaries were enlarged and cystic. Microscopically, the tumour was cystic with tubulopapillary growth characterized by narrow, elongated branching tubules. Immunohistochemically, the tumour cells expressed alpha-inhibin, while epithelial membrane antigen was not detected, indicating a sex cord-stromal origin of the tumour. Additionally, the tumour cells expressed cytokeratin and vimentin in addition to oestrogen receptor alpha and progesterone receptor.     

The site of inhibin production in ovarian neoplasms

Inhibin, a physiological product of ovarian follicle cells, normally absent in serum of postmenopausal women, is elevated in adult granulosa cell tumours of the ovary. Recently, high serum levels of inhibin were reported in carcinomas and, surprisingly, also in Krukenberg tumours of the ovary. This study attempted to determine the site of inhibin production in primary (111 cases), metastatic (13) and secondary (10) ovarian tumours by using immunohistochemistry. Positive staining in tumour cells was encountered in all cases of sex-cord- stromal cell tumours, adult (13) and juvenile (3) granulosa cell tumours, thecofibromas (10), in a lipid cell tumour (1) and a Sertoli-Leydig cell tumour (1). Primary and secondary tumours not derived from sex-cord stroma revealed no positivity in tumour cells, but in theca-like cells in the surrounding non-neoplastic ovarian stroma. A positive reaction was not observed in non-tumour-bearing ovaries of a control group. The ovarian inhibin of postmenopausal women is derived from activated sex-cord stroma or sex-cord-stromal neoplasms. Therefore, elevated serum inhibin concentrations in women with primary or secondary ovarian neoplasms with other histogenesis seem to be due to an activation of the non-neoplastic ovarian stroma. Inhibin will fail to be a tumour marker in these cases. By contrast, it will be useful in proving sex-cord differentiation by immunohistochemistry and might be used in surveillance of malignant sex-cord derived neoplasms by serum assays.     

Sertoli-Leydig cell tumour in an infertile patient after stimulated ovulation

A 36 year-old infertile female developed a stage IV (FIGO) ovarian carcinoma consisting of a poorly differentiated Sertoli-Leydig cell tumour after receiving one course of ovulation induction with follicle stimulating hormone (FSH), human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) followed by gonadotrophin-releasing hormone analogue (GnRHa). The patient died of liver metastasis and hepatic failure 4 1/2 months after first diagnosis, despite aggressive treatment consisting of debulking surgery and aggressive adjuvant chemotherapy.      

Alpha-fetoprotein-producing Immature Mediastinal Teratoma Showing Rapid and Massive Recurrent Growth in an Adult

A case of immature mediastinal teratoma in a 43 year-old Japanese man is reported. The tumor, which was multicys-tic with solid zones and measured 12times6x8cm, arose in the anterior mediastinum. The serum alpha fetoprotein (AFP) level was elevated to 5,114 ng/ml before surgery. Histologically, the solid zones showed an admixture of irregular glands lined by columnar or cuboidal epithelium set in a spindle cell stroma, some foci of primitive neural tissue, and scattered small nests of hepatoid cells. Im-munohistochemically, the hepatoid cells and epithelia lining some of the cysts showed a strongly positive reaction for AFP. Eight months after surgery, the patient died of respiratory failure caused by a rapidly growing massive recurrent tumor, which measured 40times24times13cm, in the left thoracic cavity. However, the elevated serum AFP level had been decreasing during the course of the recurrence in response to chemotherapy. The recurrent tumor showed remarkable proliferation of loose mesenchymal tissue without primitive neural tissue. These findings suggest that immature mediastinal teratoma in adults is highly malignant, and that non-AFP-producing mesenchymal tissue played a critical role in forming the rapidly growing massive recurrent tumor in the present case. Acta Pathol Jpn 42: 911–915, 1992.     

Low-grade myxofibrosarcoma: Progression in recurrence

A case of lowgrade myxofibrosarcoma with histologic progression in recurrence occurring in a 51-year-old male is described. The patient had a well-circumscribed encapsulated myxoid mass, which measured 2.5 cm at its greatest diameter, In the subcutis of the left forearm. Microscopically, the tumor was characterized by a proliferation of sparsely distributed spindle or stellate cells, curvilinear small vessels and myxoid stroma. It demonstrated mild pleomorphism without mitotic figures. The patient had the first recurrence at 3 years, which was histologically identical to the primary tumor. The patlent had a second recurrence at 11 years, which was predominantly composed of sheets of anaplastic, rounded or oval cells with focal osteoid formation. Immunohistochemically, the tumor cells in the primary and the first recurrent lesions were focally positive for vimentin. In the second recurrence, the tumor cells contained vimentin, alpha smooth muscle actin and muscle speclfic actln (HHF35). The primary lesion had a diploid DNA content with low S-phase fractions. The second recurrence showed a polyploldy. The patient was well with no evidence of disease 18 months after the second recurrence. These findings suggest that this neoplasm showed histological progression with an increasing risk of metastasis. Lowgrade myxofibrosarcoma, which commonly is misinterpreted as benign, has a tendency for histological and blalogical progression In local recurrences, underlining the importance of accurate diagnosis and wide surgical excision of the primary lesion.     

Alpha-fetoprotein production by a malignant mixed müllerian tumour of the uterus.

A case of alpha-fetoprotein production by a uterine malignant mixed müllerian tumour is described. The patient was a 68 year old woman who developed intraabdominal recurrence of a stage 1 uterine tumour which had been treated surgically seven years previously. Her serum alpha-fetoprotein was raised at 21,000 micrograms/l (normal < 10 micrograms/l) and staining with immunoperoxidase confirmed that the tumour was the site of alpha-fetoprotein production. The patient was treated with combination chemotherapy but died two weeks after the first course. This is believed to be only the second such case reported.     

Glomangiomyoma (glomus tumour) of the pancreas: a case report

Glomus tumours occur in many sites. We report the first case of a glomangiomyoma in the pancreas of a 17-year-old girl. The tumour was 5cm in diameter and consisted of rounded glomus cells, blood vessels and spindled smooth muscle cells. The glomus and smooth muscle tumour cells showed moderate diffuse cytoplasmic staining with vimentin, muscle-specific actin and smooth muscle actin. There was weak focal positivity for desmin in the spindle cell component only. The patient is alive and well with no evidence of recurrence 24 months after surgery.     

Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia')

So-called 'vascular neoplasia' (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60-year-old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node-like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit-like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL-6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL-6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon.     

Ovarian myxoma. A study of two cases with long-term follow-up

Two cases of the so-called ovarian myxoma are reported. One was from a 13-year-old girl who had a 31-year follow-up and no evidence of recurrence. The second case, from a 65-year-old woman, recurred intraperitoneally, 19 years after the surgery. Both tumors were myxoid, with round to stellate cells. Immunohistochemical, electron microscopic (EM), and DNA flow cytometric (FCM) studies were performed on formalin-fixed, paraffin-embedded tissue of the second patient on both the primary tumor and the recurrence. Tumor cells expressed vimentin and were focally positive for desmin and myoglobin. EM findings suggested a fibroblastic differentiation. An aneuploid cell population was present in the recurrent tumor by DNA-FCM studies. Only four other cases of so-called ovarian myxoma were reported to date, and the follow-up does not exceed 18 months. The authors conclude that the presence of aneuploidy and the late recurrence of one of their cases suggest that certain ovarian myxomas might behave like low-grade sarcomas. The histogenesis of this tumor remains unsettled, but similarities were found with myxomas in other locations.     

Sertoli-Leydig cell tumor of the ovary with alpha-fetoprotein production

A case of poorly differentiated Sertoli-Leydig cell tumor with elevated serum alpha-fetoprotein (AFP) levels occurred in a 17-year-old girl. No germ cell component and no heterologous elements were identified, but a retiform pattern was present. Immunohistochemical studies demonstrated immunoreactivity for AFP and testosterone in Leydig's cells only. Secretion of AFP by Sertoli-Leydig cell tumors has rarely been mentioned previously, and its mechanism is difficult to explain. Non-germ cell tumors must be considered in the differential diagnosis of ovarian tumors with elevated serum AFP levels.     

Intermediate filaments cytokeratin and vimentin in ovarian sex cord-stromal tumours with correlative studies in adult and fetal ovaries

The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.     

Ovarian spindle cell lesions: a review with emphasis on recent developments and differential diagnosis

Ovarian lesions composed of spindle cells comprise a heterogeneous group; most are neoplastic but several non-neoplastic conditions are also composed of spindle cells. This review discusses the main differential diagnoses of an ovarian spindle cell lesion, especially concentrating on the recent literature. The majority of ovarian spindle cell lesions fall into the broad category of fibromatous neoplasms whereas others in the sex cord-stromal group may also be composed of spindle cells, including thecomas, granulosa, and Sertoli-Leydig cell tumors and rarer neoplasms, such as sclerosing stromal tumor and signet-ring stromal tumor. In the recent past there have been several major contributions on various aspects of ovarian spindle cell lesions, including cellular and mitotically active cellular fibromatous lesions, smooth muscle neoplasms, and metastatic gastrointestinal stromal tumors. Other mesenchymal or epithelial tumors and mixed epithelial and mesenchymal neoplasms may also enter into the differential diagnosis of an ovarian spindle cell lesion. Several non-neoplastic lesions may be composed of spindle cells, including massive edema, ovarian fibromatosis, stromal hyperplasia, and stromal hyperthecosis. Morphology remains the mainstay in diagnosis but immunohistochemistry may be invaluable in certain circumstances, one example being the identification of a metastatic gastrointestinal stromal tumor within the ovary.     

Histological Patterns in Germ-cell Tumours associated with Raised Serum Alpha-fetoprotein (AFP)

Serum alpha-fetoprotein (AFP) was studied in 237 patients with germ cell neoplasms of the gonads and extra-gonadal sites. Whenever possible serial determinations were performed. All patients in remission had normal serum AFP. Raised serum AFP was seen in patients with active disease whose tumours contained endodermal sinus tumour (EST). This included 29 patients with testicular tumours, 11 with ovarian, 3 with mediastinal, and one with a retroperitoneal tumour. In all these patients serum AFP levels were high and correlated well with the amount of EST within the tumour. Serum AFP became normal when the disease was eradicated. There was a gradual rise with recurrence of the disease. Slightly raised serum AFP (below 60 ng/ml) was present in two patients with embryonal carcinoma examined preoperatively. In four similar cases serum AFP was normal. All patients with pure teratoma had normal serum AFP. Seventeen patients with pure seminoma whose serum was examined preoperatively had normal serum AFP at all times. These findings indicate that raised serum AFP is associated with the presence of EST within the tumour, and AFP is a good and reliable tumour marker in patients with germ cell neoplasms containing EST.     

Value of A103 (melan-A) immunostaining in the differential diagnosis of ovarian sex cord stromal tumours

AIMS: To assess A103 (melan-A) immunoreactivity in a range of ovarian sex cord stromal tumours and to evaluate it for the differential diagnosis of other neoplasms. METHODS: Paraffin embedded tissue sections from 45 sex cord stromal tumours and 44 potential histological mimics were examined immunohistochemically using the antibody A103. The sex cord stromal group included 21 adult granulosa cell tumours (AGCT), two juvenile granulosa cell tumours (JGCT), eight tumours showing Sertoli cell or Sertoli-Leydig cell differentiation, two unclassified tumours, two gonadoblastomas, one sex cord tumour with annular tubules, two steroid cell tumours, five thecomas/fibrothecomas, and two sclerosing stromal tumours. The histological mimics include 14 primary ovarian carcinomas, 13 metastatic carcinomas, four carcinoid tumours, four lymphomas, three endometrioid stromal sarcomas, two ovarian tumours of probable Wolffian origin, and one case each of small cell carcinoma, desmoplastic small round cell tumour, melanoma, and primitive neuroectodermal tumour. RESULTS: A103 immunoreactivity was identified in 25 sex cord stromal tumours including 10 AGCT, two JGCT, six Sertoli/Sertoli-Leydig cell tumours, two steroid cell tumours, three thecomas/fibrothecomas, and two sclerosing stromal tumours. Of the potential histological mimics, staining was present only in the two ovarian tumours of probable Wolffian origin and the melanoma. Immunoreactive stromal cells were noted in a minority of cases. Normal hilus cells and rete ovarii epithelium also expressed A103. CONCLUSIONS: A103 is a moderately sensitive and specific marker of sex cord stromal differentiation within the range of tumours examined in this study and as such is a valuable adjunct to other immunocytochemical markers in the assessment of diagnostically problematic ovarian tumours. The staining of normal and neoplastic Wolffian elements merits further investigation.     

Primary malignant 'triton' tumour of the lung

Two cases of malignant 'triton' tumour arising within lung parenchyma are described. The patients were a three-year-old child and a 53-year-old man. Both patients presented with shortness of breath and a large intrapulmonary mass on chest X-ray. Neither patient had a history of von Recklinhausen's neurofibromatosis. The lesions were treated by pneumonectomy. Grossly, both tumours presented as large, soft and gelatinous intraparenchymatous masses measuring 130 mm and 80 mm, respectively. Histologically, they were characterized by an atypical spindle cell proliferation embedded in an abundant myxoid stroma. Focal areas of rhabdomyoblastic differentiation characterized by large cells with abundant eosinophilic cytoplasm and occasional cytoplasmic cross-striations could be seen admixed with the atypical spindle cell elements. Immunohistochemical studies showed a focal positive reaction for S-100 protein in the atypical spindle cells embedded within the myxoid stroma, and a strong positive reaction for desmin and myoglobin in the rhabdomyoblastic areas. The child died three months after diagnosis with extension of the tumour into the thoracic cavity. The second patient has been lost to follow-up. Although rare, malignant 'triton' tumour should be considered in the differential diagnosis of primary spindle cell sarcomas of the lung.     

Low-grade fibromyxoid sarcoma

A low-grade fibromyxoid sarcoma arising in the thigh of a 16-year-old Japanese girl is described. The patient had a well-circumscribed mass measuring 3.5 cm in its greatest diameter within her left vastus medialis muscle and a 6-month history of pain. Microscopically, the tumour was not encapsulated and filtrated into adjacent skeletal muscle. The tumour was characterized by poor to moderate cellularity, a proliferation of bland-appearing spindle tumour cells, and alternating fibrous and myxoid areas with a whorled pattern of the tumour cells. Neither cellular atypia nor mitotic figures were observed. There was no tumour necrosis. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and desmin. Some cells contained alpha smooth muscle actin. They were uniformly negative for CAM5.2, epithelial membrane antigen, muscle-specific actin (HHF35), factor-VIII-related antigen, S-100 protein, neurofilament, CD34, and CD31. The tumour had a diploid DNA content with S-phase fractions of 6.6% by flow cytometry. The patient was alive with no evidence of disease 11 months after excision.     

Giant cell tumor of soft tissues. Report of two cases

We report two cases of giant-cell tumour of soft tissue (TCG-TM). The first case occurred in a 26-year-old woman presenting with a subcutaneous tumour of the left leg. Pathological study revealed a tumour comparable to benign giant cell tumour of bone. The patient is well without recurrence 10 months after the diagnosis. The second case concerned a 49-year-old man with a huge mass of the thigh. Microscopically, the tumour was composed of sheets of mononuclear and multinucleated cells. Mononuclear cells presented severe atypia and a high mitotic activity. Eighteen months later, the patient died with diffuse pulmonary metastases. TCG-TMs are uncommon and represent a distinct entity whose clinical behaviour and histological features are similar to giant-cell tumour of bone. The malignant variant is debatable. The differential diagnosis includes other tumours rich in osteoclast-like cells.     

Clinical utility of histopathology data: cancers of the testis and urinary bladder

Histopathology data form the basis of most oncological patient management. Pathology guidelines therefore recommend sets of core data items that should be reported in each specimen. The clinical utility of a particular data item depends on the clinical scenario. Awareness of how these data are used to guide patient management could enable pathologists to focus their resources on clinically important issues. For example, it is generally critical to identify even a minor nonseminomatous component in a predominantly seminomatous testicular germ cell tumour as such patients would be managed as a nonseminoma. However, this finding would be less important in a patient with a raised serum alpha fetoprotein level as such a patient would generally be managed as a nonseminoma even if the histological diagnosis is pure seminoma. In this review, we discuss the clinical utility of various histopathology parameters in the management of bladder and testicular cancer.     

Rectal leiomyosarcoma: report on two cases and a practical approach to differential diagnosis

Rectal leiomyosarcoma is an uncommon malignancy. Herein, we describe the clinicopathological features and biological behaviour of these tumours, and provide a practical approach to differential diagnosis, particularly with gastrointestinal stromal tumours (GIST). We report two cases in elderly men. In the first, the lesion was 2 cm from the anal sphincter, while it was located in the rectal ampulla in the second case. Histologically, both tumours were characterized by pleiomorphic, large spindle cells, presenting numerous mitoses and marked nuclear atypia. Immunohistochemical analysis showed that tumour cells coexpressed both actin and desmin, whereas CD117 and S100 protein were negative. The final diagnosis was leiomyosarcoma. One of the patients died of pulmonary metastasis within six months. The second patient had bone metastasis, but was lost to follow up. This report underlines the potential diagnostic problems raised by rectal leiomyosarcoma and emphasizes the role of immunohistochemistry in achieving correct diagnosis, which has important clinical, therapeutic and prognostic consequences.