Yoshio Miyazawa

Penile verrucous carcinoma with anaplastic transformation following radiotherapy. A case report with human papillomavirus typing and flow cytometric DNA studies.

We report a case of penile verrucous carcinoma with anaplastic transformation after radiotherapy. A 49-year-old man with penile verrucous carcinoma initially underwent excision and chemotherapy followed by radiotherapy when the carcinoma recurred locally. Twenty-four months after the completion of radiotherapy, the verrucous cancer transformed to an anaplastic spindle-cell carcinoma, which resulted in his death 10 months after diagnosis. Autopsy confirmed a huge hemorrhagic recurrent lesion and lung metastases. In situ hybridization with biotinylated DNA probes did not detect any type of human papillomavirus (HPV) (types 6/11, 16/18, and 31/33/51) in either the primary or the anaplastic tumor. Immunohistochemical HPV capsid antigens were also negative in both lesions. A flow cytometric analysis, using paraffin-embedded materials, showed a diploid DNA content in the excised verrucous carcinoma and an aneuploid content in the anaplastic tumor. This patient most likely had radiation-induced transformation of an anaplastic carcinoma. Wide excision and, if necessary, amputation, are preferred to radiotherapy.

PRIMITIVE NEUROECTODERMAL TUMORS OF BONE AND SOFT TISSUE : WITH REFERENCE TO HISTOLOGIC DIFFERENTIATION IN PRIMARY OR METASTATIC FOCI

Primitive neuroectodermal tumors (PNET) of the bone and soft tissue were reviewed by immunohistochemistry and partly by morphometry, focusing particularly on histologic changes in recurrent or metastatic foci, in order to elucidate their probable histogenetic relationship with Ewings sarcoma (ES) and its extraskeletal counterpart (EES). Eleven cases of bone tumor (average patient age; 15.1 yr) and 12 cases of soft tissue tumor (average patient age; 22.1 yr) which disclosed unequivocal Homer Wright rosettes and/or at least foci of ganglion cell differentiation either in a given primary tumor or metastatic (or recurrent) foci were selected from small round cell tumors primarily categorized as ES or EES. Most of the cases for which follow up biopsy samples were available disclosed prominent Homer Wright rosettes in the metastases, whereas the primary tumors showed features of ES and lacked rosettes. In only one case, Homer‐Wright rosettes were absent in the metastatic tumor. Most cases had been treated by combined intensive chemotherapy and radiotherapy, which might have influenced cell differentiation. Neural markers (neuron‐specific enolase, neurofilament protein and others) were positive in most cases. Three cases with otherwise typical histologic features of ES or EES showed minute foci of ganglion cell differentiation, as confirmed by morphometry and neural markers. These results suggest that ES (or EES) and PNET are histo‐genetically related, but represent different stages of cell differentiation.

Endometrial low-grade stromal sarcoma with ovarian sex cord-like differentiation : Report of two cases with an immunohistochemical and flow cytometric study

Two cases of endometrial low‐grade stmmal sarcoma with ovarian sex cord‐like differentiation occurring in a 39‐year‐old woman and a 42‐yearold woman are presented. Both tumors, which were intramyometrial and measured 7.5 cm and 7.0 cm in greateat diameter, respectively, showed a multinodular, ill‐demarcated, and yellowish white cut‐surface. Histologically, most parts of the tumors were composed of trabecular, cord‐like, or plexiform arrangements that were reminiscent of the growth pattern seen In ovarian sex cord tumors. Features of conventional endometrial low‐grade sttomat sarcoma were only focally observed. The tumors showed inflitrative margins and lymphatic invasion. The tumor cells were positive for vimentin, desmin, α‐smooth muscle actin, and muscle actin (HHF35).The tumors were also positive for both estrogen and progesterone receptors. Both tumors were DNA diploid as determined by flow cytometry. One patient had recurrences, Including oste olytic lesions in the pelvic bones, but had no evidence of recurrence or metastasis 11 months after the last surgery. The other patient had no evidence of tumor in a limited follow‐up. Famillarity with the neoplasm and other uterine mesenchymal tumors with ovarian sex cord‐like differentiation by gynecologists and pathologists is essential in avoiding misdiagnosis because adjuvant hormonal therapy may be effective in treating lowgrade stromal gammas.

Microcephaly and early-onset nephrotic syndrome--confusion in Galloway-Mowat syndrome.

We report a 2-year-old girl with nephrotic syndrome, microcephaly, seizures and psychomotor retardation. Histological studies of a renal biopsy revealed focal glomerular sclerosis with mesangiolysis and capillary microaneurysms. Dysmorphic features were remarkable: abnormal-shaped skull, coarse hair, narrow forehead, large low-set ears, almond-shaped eyes, low nasal bridge, pinched nose, thin lips and micrognathia. Cases with this rare combination of microcephaly and early onset of nephrotic syndrome with various neurological abnormalities have been reported. However, clinical manifestations and histological findings showed a wide variation, and there is a lot of confusion in this syndrome. We therefore reviewed the previous reports and propose a new clasification of this syndrome.

Small cell neuroendocrine carcinoma of the ovary

A 64-year-old woman (gravida 0, para 0) had a unilateral ovarian mass measuring 14 cm in its greatest diameter, which was mostly solid. Microscopically, the tumour was characterized by two predominant proliferating patterns: a carcinoid-like pattern with trabecular, tubular, glandular, or insular arrangements and a closely packed nesting pattern with central coagulation necrosis and occasional glandular arrangements. These two patterns were intermingled, and numerous mitotic figures were present. Electron microscopy showed neurosecretory granules in the cells, which were argyrophilic and positive for neuroendocrine markers (chromogranin, leu 7, neuron-specific enolase, and synaptophysin). The tumour was aneuploid by flow cytometry. The patient received chemotherapy postoperatively, developed brain and multiple bone metastases and died of disease 10 months after surgery. This tumour must be distinguished from other small cell neoplasms, especially ovarian small cell carcinoma of the hypercalcaemic type.

Case of gonadoblastoma in a 9‐year‐old boy without physical abnormalities

Background: A 9‐year‐old boy was admitted to Jikei University Hospital complaining of gradual enlarging of the left scrotal contents.

Columnar cell carcinoma of the thyroid

A case of columnar cell carcinoma of the thyroid occurring in a 50‐yearoid female is described. Histologically, the 2 cm tumor showed a prominent papillary architecture with thin fibrous cores covered by columnar cells and marked nuclear stratiflcation. It also showed microfollicular, glandular, and solid pattems. The nuclear features were different to those of conventional papillary carcinomas and similar to those of follicular tumors. The tumor was principally encapsulated with vascular and minimal capsular invaslon. The tumor cells were positive for thymglobulin. The tumor was DNA diploid with a low S phase fraction as determined by flow cytometry. The patient had no lymph node or distant metastasis. The patient was well and without disease 9 months after surgery. The possibility that the neoplasm is one of poorly differentiated thyroid carcinomas rises.

Yolk sac tumour of the ear

We report the second known case of yolk sac tumour of the external auditory canal, occurring in an eight‐month‐old girl. The excised tumour demonstrated histopathological and immunohistochemical features identical to those of yolk sac tumours of gonadal origin. The tumour was aneuploid by flow cytometry. The patient received chemotherapy post‐operatively and has had no evidence of disease 13 months after surgery.

Immunohistochemistry of molar and non‐molar placentas with special reference to their differential diagnosis

An immunohistochemical study analyzing distributions of β‐subunit human chorionic gonadotropin (βHCG), human placental lactogen (HPL), placental alkaline phosphatase (PLAP), and monoclonal anti‐cytokeratin (PKK1) was undertaken to determine whether the reactivity of these antigens might assist in the differential diagnosis of molar and non‐molar hydropic placentas. A total of 16 complete hydatidiform moles, 15 partial hydatidiform moles, 12 hydropic abortuses and 39 non‐hydropic placentas with gestational age ranging from 4 to 40 weeks was examined. In both the complete and partial moles, many syncytiotrophoblasts stained for βHCG, HPL, PLAP and PKK1 although the staining intensity of βHCG in the partial moles was weak compared with the complete moles. The staining patterns in the hydropic abortuses were almost the same as those in the normal first trimester placentas and had no distinct features from the partial moles. Trophoblastic hyperplasia is an essential feature in differentiating partial moles from hydropic abortuses. With regard to the immunostaining patterns of these antibodies, there was no significant difference to enable delineation between partial and complete moles, or between a hydropic abortus and a partial mole. Monoclonal anti‐cytokeratin was most sensitive for trophoblasts, but less specific for intermediate trophoblasts than HPL. Although an immunohistochemical study using antibodies against βHCG, HPL, PLAP and PKK1 is very useful for characterizing various trophoblasts, it is considered that an immunohistochemical study may not be a suitable tool for the differential diagnosis of molar and non‐molar hydropic placentas.

Angiomatoid Malignant Fibrous Histiocytoma An Immunohistochemical, Ultrastructural, and Flow Cytometric Study of Two Cases

This study reports the immunohistochemical, ultrastructural, and flow cytometric find ings of two cases of angiomatoid malignant fibrous histiocytoma that developed in the subcutis of the temple of a 10-year-old girl and the shoulder region of a 5-year- old boy. The neoplasm of the temple developed a local recurrence 6 months after the initial excision. Both patients were well and free from tumor at 24 months and 12 months, respectively. Immunohistochemically, many tumor cells of both cases posi tively expressed vimentin, desmin, HHF-35, and KP1. In one case many tumor cells also showed lectin binding for ulex europaeus agglutinin 1, and the other case pre sented ultrastructural features of immature endothelial cells. All tumors, including the recurrent lesion, were diploid. Divergent antigenic phenotypes along with many types of cells were considered; including myogenic cell, fibroblastic cell, and immature endo thelial cell. This study suggests that angiomatoid malignant fibrous histiocytomas show a wide range of pluripotential differentiation. Int J Surg Pathol 2(2):99-104, 1994