Eric S. Wargotz

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.

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 welldemarcated 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.

Metaplastic carcinomas of the breast. III. Carcinosarcoma

The clinical and pathologic features of 70 examples of carcinosarcoma (CS) of the breast are reported. Thirty‐three neoplasms had infiltrating carcinoma, seven had in situ carcinoma, and 28 had both admixed or contiguous with the sarcomatous component. Squamous carcinoma, present in 15 neoplasms, was the exclusive epithelial component of two. The admixed carcinoma often appeared distinct from the sarcoma component; however, at high magnification transitional differentiation zones and more subtle merging of infiltrating carcinoma with sarcoma were present in most neoplasms. A total of 40 neoplasms were studied by immunohistochemistry for keratins, EMA, vimentin, S‐100 protein, and actin. The sarcomatous component in 55% of CS was immunoreactive for keratin, and 98% were immunoreactive for vimentin. A majority were also immunoreactive for actin (77%), and S‐100 protein (55%). Ultrastructural examination of the sarcoma in eight neoplasms yielded variable nonspecific findings compatible with sarcoma. These findings indicate biphasic differentiation by cells possessing epithelial and mesenchymal characteristics and suggest myoepithelial origin or differentiation. The cumulative 5‐year survival rate for CS was 49%, worse than for other forms of metaplastic carcinoma. The respective 5‐year survivals for TNM clinical Stages I, II, and III were 100%, 63%, and 35%. Of patients with axillary dissection, 26% had metastases to axillary lymph nodes with carcinoma as the most frequent component to metastasize. Metastasis was an ominous sign as 33 of 34 patients who developed metastases died from tumor. Local recurrence was not as ominous as 40% who had only local recurrence subsequently died from tumor. Size and microscopic circumscription were also significant prognostic factors.

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.

Flow cytometric analysis of granulosa tumors

Paraffin blocks from 17 granulosa tumors, nonmetastatic (n = 10) and metastatic (n = 7), were analyzed by flow cytometry. Three neoplasms, one with and two without metastases, were found to have cells with an abnormal DNA (DNA aneuploid) content. The occurrence or absence of DNA aneuploid cells did not predict behavior. In addition, there was no correlation of tumor DNA content with tumor size or patient age at the time of surgery. There was no significant difference in cell proliferation (%S + %G2/M) between metastatic and nonmetastatic DNA diploid tumors, however, there was an increase in cell proliferation in tumors with a DNA aneuploid stemline. Granulosa tumors are low‐grade neoplasms. At least 90% are seen in Stage I, and metastasis occurs subsequently in 5% to 15% of these cases. Features of Stage I neoplasms associated with subsequent metastasis in some reports, but not all, are involvement of the capsule (Stage IC), large size, and high mitotic rate.1–5 Providing definitive statements about the behavior of granulosa tumors is hampered by their rarity, the subjectivity of the diagnosis, and their sluggish behavior. We attempted to determine if flow cytometric analysis of DNA could identify granulosa tumors with metastatic potential. We compared DNA histograms from ten Stage IA granulosa tumors that did not metastasize during 22 to 47 years of follow‐up with seven granulosa tumors that showed malignant behavior.

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

&NA; 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 lowgrade fibrosarcomas‐malignant fibrous histiocytomas showed mild (1 +) cytologic atypia, and 69% of the highgrade 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 slowgrowing, 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 highgrade lesions developed distant metastases.

Granulomatous angiopanniculitis of the breast

The clinical and pathologic features of six examples of nonnecrotizing granulomatous angiopanniculitis (GAP) of the breast are reported. The patients presented with a solitary ill-defined breast mass causing clinical suspicion of carcinoma. Histopathologically, all lesions consisted of multiple nonnecrotic, noncaseous granulomas with a giant cell component predominantly involving the subcutaneous adipose tissue, extending into the underlying mammary tissue without affecting lobules or ducts. A nonleukocytoclastic lymphocytic angiitis involved small vessels and capillaries. None of the patients had a history of an autoimmune disorder or had previous diagnoses of erythema nodosum or multiforme, leukocytoclastic or nonleukocytoclastic vasculitis, or Weber-Christian disease. Treatment was limited to biopsy in all six patients. Studies for infectious agents on specimens were negative. Five of the six patients developed one or more recurrences in the breast or elsewhere on the body. Four patients experienced spontaneous regression of their recurrent lesions. GAP appears to be a self-limited disorder of uncertain etiology which involves the breast and other sites. It may represent a variant of Weber-Christian disease, as the two diseases share similar clinical and histologic features. GAP must be distinguished from causes of granulomatous inflammation of the breast for which specific medical therapy is available.

Smooth Muscle and Nerve Sheath Tumors of the Breast: A Clinicopathologic Study of 45 Cases

The clinical and pathological features of 22 smooth muscle tumors and 23 nerve sheath tumors of the breast are presented. The smooth muscle tumors included 18 leiomyomas and 4 leiomyosarcomas. Two types were found: those superficial in the nipple or in the skin overlying the breast and those located within the breast parenchyma. Superficial leiomyomas were small and had ill-defined, infiltrating margins. Leiomyomas located within the breast were circumscribed and larger than the superficial ones. Mitotic activity did not exceed 1 mitotic figure per 10 high-power field and only 2 of the 18 showed 1 + and 2 + atypia. None recurred after local excision. The four leiomyosarco mas had 2 + and 3 + nuclear atypia and mitotic activity ranging from 3 to 28 mitotic figures per 10 high-power field. Recurrences occurred in two, but none metastasized. Nerve sheath tumors included 5 neurilemomas, 15 neurofibromas and 3 malignant schwannomas. All neurilemomas were encapsulated and showed no mitotic activity or cytologic atypia. Of the 15 neurofibromas, 6 were encapsulated, 4 had circumscribed margins with focal infiltration, and 2 had infiltrative margins. Focal cytologic atypia was seen in 4. All 3 malignant shwannomas had infiltrative margins, nuclear atypia, and noticeable, often abnormal, mitotic figures. Two of the 11 patients with neurofi broma had von Recklinghausens disease and developed recurrences. None of the 3 patients with malignant schwannoma developed a recurrence. Int J Surg Pathol 2(2): 85-92, 1994