Sertoli-Leydig tumors of the ovary. A clinicopathologic study of 64 intermediate and poorly differentiated neoplasms.

The clinical and pathologic features of 64 Sertoli-Leydig tumors of the ovary with intermediate and poor differentiation were studied. The neoplasms occurred mainly in young women. Fifty-four percent of the patients presented with clinical evidence of a hormonally active tumor, and 38% were virilized. The remaining 46% had nonspecific symptoms. Sixty-two patients had tumors confined to one ovary at operation (Stage Ia), while only two patients presented with pelvic metastases (Stage III). The prognosis was generally favorable; the 5- and 10-year actuarial survival rates were 92%. Unilateral salpingo-oophorectomy was effective treatment for Stage Ia Sertoli-Leydig tumors in young women. Microscopically, 44 of the neoplasms were of intermediate differentiation and 20 were poorly differentiated. Heterologous elements (mucinous epithelium, striated muscle, cartilage) were present in 16 neoplasms. The pathologic features that correspond with development of metastases were poor differentiation, the presence of heterologous mesenchymal elements, frequent mitotic figures in stromal cells, and rupture of the neoplasm.

Cystadenofibromas of the ovary with epithelial atypia.

Epithelial atypia is rarely encountered in ovarian cystadenofibromas. Ten examples are reported with cytological features identical to serous tumors with low malignant potential. In two neoplasms the epithelium resembled an atypical endometrial hyperplasia, and one of these had squamous metaplasia. These two neoplasms probably qualify as endometrioid tumors of low malignant potential. None of the 10 patients had recurrence following excision of their neoplasm, and no similar patients have been encountered with neoplasms in more advanced stages. Even though aggressive behavior has not yet been established, the histologic features suggest a low degree of malignant potential and long-term follow-up of patients is warranted. Cystadenofibromas iwth epithelial atypia probably have less malignant potential than serous tumors of low malignant potential possessing the same epithelial characteristics because cystadenofibromas with atypia have less epithelial surface area and the epithelium is enveloped by connective tissue more than it is in serous tumors of low malignant potential.

Granulosa tumors of the ovary in children: a clinical and pathologic study of 32 cases.

Granulosa tumors in children differ histologically from those occurring in adults. Of 32 neoplasms occurring in girls 16 years of age or younger, 26 were juvenile granulosa tumors and three were cystic granulosa tumors; only three neoplasms resembled typical adult granulosa tumors. The juvenile granulosa tumor differs from the typical adult form in that it is composed of larger cells and has luteinization of its cellular components. Two-thirds of the patients had endocrine abnormalities. Fifteen of 20 premenarcheal patients had isosexual precocious pseudopuberty. Of the 12 postmenarcheal girls, seven had menstrual abnormalities and two of the seven were virilized. All 32 patients had Stage Ia tumors. The clinical outcome was generally favorable since only two of 26 patients with follow-up developed a recurrence. Unilateral salpingo-oophorectomy is appropriate treatment for girls with Stage Ia granulosa tumors; 23 of 25 patients treated by unilateral salpingo-oophorectomy were well without recurrence at last contact.

Microglandular adenosis of the breast. A clinicopathologic study of 11 cases with ultrastructural observations.

The clinical and pathologic features of 11 examples of microglandular adenosis of the breast are presented. Microglandular adenosis is a rare, benign lesion that is easily confused with carcinoma. It is characterized by a concentrated proliferation of round glands with open lumens in a densely homogeneous stroma that clearly delineates microglandular adenosis from the adjacent uninvolved breast. The glands are lined by a single layer of cells with distinctly vacuolated or granular cytoplasm. Ultrastructurally, the single layer of epithelial cells lacks cytoplasmic protrusions and is surrounded by a thick multilayered basement membrane. Light- and electron-microscopic features that help distinguish microglandular adenosis from well-differentiated (tubular) carcinoma and sclerosing adenosis, entities with which it is easily confused, are discussed.

Endometrioid proliferative and low malignant potential tumors of the ovary. A clinicopathologic study of 46 cases.

We evaluated 41 endometroid neoplasms with features intermediate between a benign endometrioid tumor and endometrioid carcinoma. Although these tumors showed various degrees of epithelial proliferation, they lacked the destructive stromal invasion of carcinoma. Intermediate endometrioid tumors were subdivided into proliferative endometrioid tumors (PET), endometrioid tumors of low malignant potential (ETLMP), and ETLMP with microscopic areas of invasion. PET were adenofibromas with solid aggregates of epithelial proliferation not exceeding 5 mm in any dimension, whereas ETLMP either had noninvasive cytologically malignant epithelium or aggregates of atypical epithelium measuring at least 5 mm in any dimension uninterrupted by fibromatous stroma. Of the seven PET, five were purely adenofibromatous, while two were mixtures of adenofibromatous and papillary components. Of the 31 ETLMP, 12 were adenofibromatous and 19 were either purely papillary or had mixtures of papillary and adenofibromatous components. An additional three ETLMP had one or more areas of microscopic invasion of the stroma in the form of an irregular or cribriform infiltration by atypical glands, often with squamous differentiation. These three neoplasms were designated "ETLMP with microinvasive carcinoma." The only neoplasm with extraovarian implantation at presentation, however, was an ETLMP with mixed adenofibromatous and papillary features, without microinvasion. None of the other patients with ETLMP had a metastasis or developed one within a follow-up period of between 0.8 and 11.2 years. Because they are very low-grade neoplasms, ETLMP should be separated from endometrioid carcinoma and not confused with PET, because PET have no malignant potential.

Dysgerminoma with syncytiotrophoblastic giant cells. A histologically and clinically distinctive subtype of dysgerminoma.

The clinical and pathological features of six dysgerminomas containing syncytiotrophoblastic giant cells were studied; these represented 3% of the dysgerminomas in the AFIP files. Syncytiotrophoblastic giant cells, the distinguishing histological feature, were present either in clusters or were distributed diffusely. Human chorionic gonadotropin was demonstrated immunocytochemically within the cytoplasm of the syncytiotrophoblastic giant cells in both of the two tumors tested for it. Serum or urine gonadotropin titers, measured in four patients, were elevated in three, and two of these were thought to have ectopic pregnancies. All of the dysgerminomas were Stage Ia, and the six patients were well 1-14 years after treatment.

Myofibroblastoma of the breast. Sixteen cases of a distinctive benign mesenchymal tumor.

The clinical and pathologic findings of 16 examples of a distinctive stromal tumor of the breast designated as "myofibroblastoma" are reported. Eleven of the 16 patients were men, and the average age at presentation was 63 years. Fourteen were treated by local excision and two by simple mastectomy. None of the lesions recurred or metastasized. The tumors were grossly nodular and well-demarcated from the surrounding mammary tissue. Ducts and lobules were not engulfed by the neoplasm. Microscopically, the lesions were formed by uniform, slender, bipolar spindle cells haphazardly arranged in fascicular clusters separated by broad bands of hyalinized collagen. Ultrastructural examination of four lesions identified a predominance of myofibroblasts. Immunoreactivity for S-100 protein and cytokeratin was absent in the 10 tumors examined, but desmin immunoreactivity was focally present in three lesions. The differential diagnosis of myofibroblastoma includes reactive processes and benign neoplasms such as nodular and proliferative fascititis, fibromatosis, spindle-cell lipoma, neurofibroma, neurilemmoma, and leiomyoma. Malignant neoplasms such as stromal sarcoma, malignant fibrous histiocytoma, and spindle-cell or metaplastic carcinoma should not be confused with a myofibroblastoma. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.

Infiltrating syringomatous adenoma of the nipple. A clinical and pathological study of 11 cases.

The clinical and pathologic findings of 11 infiltrating syringomatous adenomas of the nipple (ISA) were studied. All neoplasms were composed of small ducts and solid strands of epithelial cells surrounded by desmoplastic stroma. Ten of the 11 invaded the smooth muscle of the nipple, four extended to underlying breast tissue, and one showed perineural invasion. All lesions had an infiltrative margin, but 10 were treated successfully by local excision, even though five (45%) recurred. None metastasized. ISA must be distinguished from nipple duct adenoma and tubular carcinoma. Its clinical significance lies primarily in its recognition as a distinctive benign neoplasm. In the past, a variety of terms have been used to describe this lesion, whether it occurred in the skin, nipple, or substance of the breast. "Infiltrating syringomatous adenoma" is the preferred term to avoid using "carcinoma" for lesions involving the breast.

Fibromatosis of the breast. A clinical and pathological study of 28 cases.

The clinical and pathologic findings of 28 examples of fibromatosis of the breast not involving the deep fascia or chest wall are reported. Five of the 20 lesions treated by local excision recurred. Recurrences developed within a 4 to 8 month period following surgery in four of the five instances, and 6 years after surgery in one instance. One lesion recurred five times over a period of 3 years. None of the patients died from their disease, and none developed a metastasis. Those lesions that recurred had been inadequately excised initially, since surgical margins showed fibromatosis. Specific histological features, such as size, cellularity, atypia, and mitotic figures, were not helpful in predicting recurrence. Although local excision appears to have been adequate in the majority (75%) of the patients, the infiltrative nature of fibromatosis necessitates documentation of tissue margins in order to avoid the possibility of recurrence. The differential diagnosis includes benign reactive processes (such as keloid and nodular fasciitis), fibrous histiocytoma, low-grade spindle-cell (metaplastic) carcinoma, and fibrosarcoma.

Fibrosarcoma-malignant fibrous histiocytoma of the breast. A clinicopathological study of 32 cases.

We report the clinical and pathologic features of 32 sarcomas of the breast with features spanning the spectrum of fibrosarcomas-malignant fibrous histiocytomas. Neoplasms were categorized as high- or low-grade lesions depending on a combination of the degrees of atypia and mitotic activity. The majority of high-grade lesions had marked (3+) nuclear atypia and at least five mitotic figures per 10 hpf. High-grade lesions with moderate (2+) nuclear atypia had a mitotic activity of six or more mitotic figures per 10 hpf. All low-grade lesions had five or fewer mitotic figures per 10 hpf, and none had a score of the nuclear grade times mitotic figures of more than 10. The average mitotic activity in low-grade lesions was two mitotic figures per 10 hpf; the high-grade lesions had 12 mitotic figures per 10 hpf. Sixty-nine percent of the low-grade fibrosarcomas-malignant fibrous histiocytomas showed mild (1+) cytologic atypia, and 69% of the high-grade lesions showed severe (3+) cytologic atypia. The herringbone pattern was associated with a more favorable prognosis than the malignant fibrous histiocytoma pattern. Compared to the high-grade lesions, low-grade fibrosarcomas-malignant fibrous histiocytomas were slow-growing, produced fewer recurrences, and did not metastasize. Of the 16 women with low-grade lesions, all were free of tumor at last contact, despite recurrence in more than half of the patients. In contrast, 31% of the patients with high-grade lesions died of tumor, and 13% were alive with disease. Twenty-five percent of women with high-grade lesions developed distant metastases.

Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.

The clinical and pathologic features of 26 examples of a histopathologically distinct form of metaplastic carcinoma of the breast are reported. All neoplasms had overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic giant cells. Therefore, we designate this distinctive form of metaplastic carcinoma as "matrix-producing carcinoma" (MPC). All patients were women, the average age was 58 years, and all patients were eligible for a minimum of 5 years follow-up (mean follow-up period, 8.6 years). Twenty-three patients were treated by a form of mastectomy and three were treated by local excision. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate for MPC was 68%. All of the nine lesions that recurred did so within 2.5 years of initial therapy. Eight of these patients (89%) died from tumor within 4 years of initial therapy. The ninth was alive at last contract. Radiation and chemotherapy were of limited effectiveness. Significant features of the neoplasm associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia. Ultrastructural examination of one case and immunohistochemical evaluation of 12 cases revealed MPC to have myoepithelial characteristics.

Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells.

The clinical and pathologic features of 29 examples of mammary metaplastic carcinoma with osteoclastic giant cells (OGC) in the stroma are reported. A bland spindle cell or sarcomatous component dominated these neoplasms, although infiltrating duct carcinoma was present in 23 cases, and intraductal carcinoma was present in six cases. In all 29 neoplasms, the carcinoma was admixed or contiguous with the stroma. Osteoclastic giant cells were admixed within the cellular stroma, and were intimately associated with prominent thin-walled vessels. Hemorrhage and hemosiderin deposition were common. Osteoclastic giant cells were immunoreactive for vimentin and, to a lesser extent, actin, and uniformly not immunoreactive for keratins, confirming their mesenchymal nature. The stromal component of 63% of neoplasms tested was immunoreactive for keratin, 33% was immunoreactive for epithelial membrane antigen, 54% reacted for S-100 protein, 84% reacted for actin, and 100% was immunoreactive for vimentin. Nineteen neoplasms had osteoid, bone, or cartilage, but these were a prominent component in only five neoplasms and OGC were not limited to these areas. The disease-specific cumulative 5-year survival rate for patients with metaplastic carcinoma with OGC was 68%, similar to rates for patients with matrix-producing carcinoma (68%), spindle cell carcinoma (64%), and squamous carcinoma of ductal origin (63%), but notably different from that of patients with carcinosarcoma (49%). Of 17 women with axillary node dissection, only two had metastases. Eleven women developed distant metastases, most commonly to the lungs. Metastasis present at or following initial surgery was an ominous sign, as all 11 women with metastases died from tumor. Size and microscopic circumscription were significant factors in predicting disease progression.

Malignant germ cell tumors of the ovary.

This article reviews 281 malignant germ cell tumors of the ovary from the Armed Forces Institute of Pathology and highlights their distinctive clinical and pathologic features. Emphasis is placed on the importance of a combined therapeutic approach utilizing surgery, chemotherapy, and radiation. The rationale for unilateral salpingo-oophorectomy in conjunction with chemotherapy for certain types of neoplasm confined to one ovary (stage 1a) is emphasized, and the role of human chorionic gonadotropin and alpha-fetoprotein as tumor markers in the management of patients with these tumors is discussed.

Mitotically active leiomyomas of the uterus.

Seventy-three smooth-muscle tumors of the uterus, with five to nine mitotic figures per 10 high-power fields but lacking cytologic atypia, were studied. Pathologic features assessed included necrosis, hemorrhage, vascular intrusion, abnormal mitoses, and the number of mitotic figures. Vascular ingrowth by the tumor was present in 11 neoplasms. Follow-up ranged from 23 months to 15 years, with all patients alive and well at last contact. In 14 patients, myomectomy was the only treatment. Thirteen of these patients demonstrated no subsequent residual or recurrent tumor. One woman developed a persistent or recurrent mitotically active leiomyoma 8 years after myomectomy. We conclude that mitotically active smooth-muscle tumors of the uterus, having five to nine mitoses per 10 high-power fields and no cellular atypia, have a metastatic rate too low to be regarded as sarcomas. Hysterectomy need not automatically follow myomectomy if follow-up is done.

Metaplastic carcinomas of the breast. II. Spindle cell carcinoma.

The clinical and pathologic features of 100 examples of spindle cell carcinoma (SpCC) of the breast are reported. Eighty-three neoplasms contained overt carcinoma; 72 had infiltrating ductal or intraductal carcinoma and in 11 the carcinomatous component was purely squamous. Seventeen neoplasms lacked overt carcinoma, but were identified as SpCC by immunoreactivity for keratin and the typical bland spindle cell proliferation forming a variable complex of fibrocollagenous stroma with feathered, myxoid, angioid, and storiform patterns. Areas of epithelium merging imperceptibly with the spindle cell component were commonly observed. Sixty neoplasms were studied by immunohistochemistry for the presence of keratin, epithelial membrane antigen (EMA), vimentin, S-100, and actin. The spindle cell component in 98% of SpCC was immunoreactive for keratin. Most were also immunoreactive for vimentin and actin, and in approximately one half, S-100 immunoreactivity was noted. These findings, in conjunction with histopathologic features, and ultrastructural observations from three cases, support myoepithelium as an integral component of SpCC. The cumulative 5-year survival rate for SpCC was 64%, better than survival rates usually reported for metaplastic carcinomas. Of 47 patients with axillary dissection, only 6% had metastases to axillary lymph nodes. Development of metastasis was an ominous sign as 29 of the 30 patients who developed metastases died from tumor. Local recurrence was not as ominous as only 29% who had only local recurrence subsequently died from tumor. The difference in size between tumors that recurred (mean, 5.0 cm) and those that did not (mean 3.7 cm), and the presence or absence of complete microscopic circumscription, were both significant prognostic factors.

A comparative morphometric and cytophotometric study of endometrial hyperplasia, atypical hyperplasia, and endometrial carcinoma.

The DNA content and nuclear measurements of five groups of endometrial proliferations--proliferative endometrium (PE), simple hyperplasia (SH), atypical hyperplasia (AH), well-differentiated carcinoma (WDC), and poorly differentiated carcinoma (PDC)--were compared using 14 descriptors in a stepwise discriminant analysis. Classification using the discriminant rules agreed with the pathologic interpretation for 78% of the specimens. All PEs were assigned to the correct group, and 97% of benign endometria and carcinomas were correctly classified as benign or malignant. Only two of 39 hyperplasias (5%) were misclassified as malignant, and only one of 36 carcinomas was classified as benign. In the difficult distinction between AH and WDC, using all descriptors for the five groups, only 68% of the AH and 60% of the WDC classifications were in agreement with the pathologist of record. However, when discriminant rules addressing only AH and WDC were used, 37 of 39 AHs and WDCs were in concordance. This suggests that a morphometric distinction between AH and WDC is feasible.

Diagnostic considerations in molar gestations.

Hydatidiform moles (HMs) are classified as partial or complete based on a combination of gross, histologic, and karyotypic features. Adherence to strict and reproducible diagnostic criteria is needed to ensure accurate diagnosis and minimize interpathologist variability. Using the kappa statistic as a measure of agreement, the morphologic, flow cytometric, and clinical features of 80 cases of HM or suspected HM were analyzed sequentially by three pathologists to evaluate intrapathologist and interpathologist variability. Poor interpathologist agreement was obtained when histology alone was used for diagnosis. The combination of gross morphology and histology resulted in poor to good agreement. Good interpathologist agreement was obtained, however, when objective data (DNA content determined by flow cytometry) were included in the analysis. Our data indicate that pathologist concordance is maximized when the diagnosis is based on a combination of morphology and DNA content.

Flow cytometric analysis of endometrial stromal sarcoma.

Twenty-two endometrial stromal sarcomas were studied by flow cytometric analysis and the results were correlated with surgical stage, nuclear grade, mitotic index, and recurrence. Ploidy determination was not helpful in predicting recurrence in patients with Stage I disease because all 14 were diploid. Only 2 of the 22 tumors were aneuploid; both were high-stage neoplasms. Cell proliferation (%S or %S + %G2/M) did not significantly correlate with vascular invasion, nuclear grade, mitotic index, or surgical stage. Of the 13 Stage I neoplasms with follow-up data, three recurred. The mean proliferation index (%S + %G2/M) of those that recurred was 12.81 +/- 0.47, which did not differ from those that did not recur (mean 12.25 +/- 4.11).

Well-differentiated (tubular) carcinoma of the breast. A clinicopathologic study of 145 pure and mixed cases.

In this study, 145 well-differentiated (tubular) carcinomas were divided into two groups: 90 pure tubular carcinomas and 55 which were mixtures in that they contained a component of infiltrating duct carcinoma occupying less than half the tumor. Axillary lymph node metastases developed in 29% of women in the mixed group, but occurred in only 6% of the pure group. The prognosis was good in both groups, with five-year-actuarial survival rates in the pure and mixed groups of 100% and 93%, respectively. Residual carcinoma was present in the mastectomy specimen in 28% of the pure group, and in 40% of the mixed carcinomas. In addition, there was a recurrence rate of 50% in patients with pure tubular carcinoma treated by excisional biopsy. These features indicate simple excision of tubular carcinoma is likely to be inadequate therapy and that a mastectomy is warranted. Axillary node dissections should be done when there is a component of infiltrating duct carcinoma because of the increased risk of axillary lymph node metastasis.

Isoantigen ABH in cervical intraepithelial neoplasia.

The purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. The correlation between the morphologic diagnosis and the results of the RCA test was limited. The percentages of tissues giving positive (+) or positive-negative (+/-) reactions were very similar in intraepithelial neoplsia (59.2%) and normal squamous epithelium (58.4%). The relationship of the RCA test results and behavior of the lesion was not studied.