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Japanese Journal of Clinical Oncology Pages 46-50

Spindle Cell Carcinoma of the Breast
Introduction
Subjects and Methods
Results
   Clinical Findings
   Microscopic and Ultrastructual Findings
Discussion
References

Spindle Cell Carcinoma of the Breast

Spindle Cell Carcinoma of the Breast Michio Maemura1, Yuichi Iino1, Tetsunari Oyama2, Toshiaki Hikino2, Takao Yokoe3, Hiroyuki Takei1, Jun Horiguchi1, Susumu Ohwada2, Takashi Nakajima2 and Yasuo Morishita1

Second Departments of 1Surgery and 2Pathology, and 3Department of Emergency and Critical Care Medicine, Gunma University School of Medicine, Maebashi, Gunma, Japan

Spindle cell carcinoma is a rare breast tumor. We present herein three cases of spindle cell carcinoma of the breast and review its characteristics from the literature. Spindle cell carcinoma frequently forms a large and well-circumscribed tumor with gross cyst formation. Histologically, its dominant component is of sheets of spindle shaped cells, and it includes such contiguous carcinoma components as squamous differentiation or invasive ductal carcinoma. Estrogen receptor expression and lymph node metastasis tend to be low. Despite the sarcomatous features, spindle cells are likely to be derived from epithelial cells of mammary glands. Immunohistochemical and ultrastructural examination demonstrated the expression of keratin and the desmosome-like junctional structure in the spindle cell components. Relatively favorable prognosis is expected in spindle cell carcinoma of the breast compared to common breast carcinoma.

Key words: spindle cell carcinoma - breast cancer - cystic formation - carcinosarcoma

Introduction

Spindle cell carcinoma is an unusual neoplasm commonly observed in the oral cavity (1) and the larynx (2). However, on rare occasions it occurs in the breast (3,4). Spindle cell carcinoma consists of dominant spindle shape cells together with in situ and/or ductal, lobular, squamous, or mixed infiltrating carcinoma (5). Since the histological arrangement of the spindle cell component resembles sarcoma, the category of `spindle cell carcinoma' has been included in carcinoma with pseudosarcomatous metaplasia, carcinosarcoma, or metaplastic carcinoma (6). Despite its sarcomatous features, immunohistochemical studies have recently suggested that spindle components are likely to be derived from epithelial cells (4,5). We present herein three cases of breast spindle cell carcinoma with a cystic formation and review its characteristics from the literature.

Subjects and Methods

All breast tumors originally coded as carcinosarcoma or spindle cell carcinoma in Gunma University Hospital were retrieved and reviewed. A total of 12 cases were identified from 1962 to 1995. Neoplasms were eventually classified as spindle cell carcinoma if in situ and/or ductal, lobular, squamous, or mixed infiltrating carcinoma was contiguous or subtly merged with sheets of spindle-shaped cells. Tumors in which spindle cell components comprised less than half of the entire tumor were excluded from the category of spindle cell carcinoma. Clinical data of patients were analyzed in conjunction with characteristics such as tumor size, contour, and lymph node metastasis. The content of estrogen receptor (ER) and progesterone receptor (PR) in the tumors was evaluated by using the dextran-coated charcoal method.

Immunohistochemical analysis for keratin and vimentin was carried out with the avidin-biotin peroxidase complex (ABC) method using formalin-fixed paraffin-embedded tissue sections. Monoclonal anti-keratin antibody KL-1 (Immunotech, Marseille, France) and monoclonal anti-vimentin antibody M0725 (DAKO JAPAN, Kyoto, Japan) were used for this study. KL-1 was known to react to a variety of cytokeratin molecules, mainly 58 kDa cytokeratin. Conventional electron microscopic observations were made on the last case (Case 3).

Results

Among the 12 cases recorded as carcinosarcoma or spindle cell carcinoma of the breast, three were eligible for this study. Two cases were excluded from this study because of their heterologous metaplastic features with little spindle component. Six cases were classified as invasive ductal carcinoma since their spindle cell components comprised less than half of the entire tumor. One case could not be reviewed due to the lack of the original slide. Three patients with spindle cell carcinoma have been followed up since operation.

Clinical Findings

The clinical characteristics in the three cases of spindle cell carcinoma are summarized in Table 1. Two patients were premenopausal women and one was postmenopausal. The age ranged from 48 to 63 years (average 54 years). Two lesions occurred in the right breast and one in the left breast. The tumors were located in the upper outer quadrant of the breast and showed gradual enlargement prior to the patients visiting our hospital. The tumors were well-defined, with cysts which were clearly detected by ultrasonograms (Fig. 1). Their sizes ranged from 5.2 to 9.0 cm. No distant metastasis was found in any patients.


Figure 1. Ultrasonogram in Case 3. A gross cyst is observed in the center of the tumor. The dotted line indicates the large diameter of the tumor. Scale: 1 cm per small division.

The preoperative diagnosis was stage IIIa breast cancer according to the Japanese clinical TNM (tumor-node-metastasis) classification system (7); this is fundamentally the same as the TNM classification (UICC: classified 1972, confirmed 1978). Two patients underwent an extended radical mastectomy with parasternal dissection and one underwent a modified radical mastectomy. The cut surfaces of all specimens were elastically firm and well- circumscribed with gross cysts (Fig. 2). Neither ER nor PR was detected in any tumors. All patients received adjuvant chemotherapy and one patient received adjuvant endocrine therapy of tamoxifen. No recurrence has occurred since the operation.


Figure 2. Cut surfaces of the tumors in Case 2 (a) and Case 3 (b). In each case, a gross cyst is visible in the center of a large and well-circumscribed tumor. Scale in cm.

Microscopic and Ultrastructual Findings

Microscopic findings by HE staining of the three tumors were basically similar. Briefly, the dominant component of the tumor was the bundles of spindle-shaped cells (Fig. 3). Some tumor cells possessed atypical nuclei and were arranged in a solid nest. Invasive ductal carcinoma components were found in the tumors of Cases 1 and 2, shown for Case 2 in Fig. 3 (b). Squamous differentiation, i.e. keratinization and intercellular bridging, was observed in the nest of spindle cells in Case 3 [Fig. 3 (c)]. However, these carcinomatous components comprised less than half of the entire tumor. The ratios of spindle cell component to carcinomatous component were 1:1 in Case 1, 2:1 in Case 2, and 8:1 in Case 3.


Figure 3. Microscopic finding of the tumor from Case 1 (a), 2 (b), and 3 (c). Most of the tumor cells are spindle-shaped. Invasive ductal carcinoma (b) and squamous differentiation (c) are observed contiguous with the spindle cell component. Intraductal components and tumor necrosis were observed in all cases. Cysts were microscopically composed of hemorrhage, necrosis, and exudates, partially surrounded by tumor cells and granulation tissues. Chondroid and/or osseous metaplasia were not observed in these tumors. These microscopic findings established the histological classification of the tumor as spindle cell carcinoma.

Table 1 Summary of three patients with spindle cell carcinoma of the breast
Case
no.


 Age



 Tumor size on
palpation (cm)		 TNM, stage



 Operation



 Tumor size
(cm)

 Gross tumor
feature


 Cyst size (cm)

 n



 ER/PR



 Follow-up
duration


 Clinical
course
1


 51


 5.2 x 3.6


 T3aN1bM0, IIIa

 Extended


 3.2 x 2.8 x 3.0 Well-circumscribed
tumor with cyst

 1.5 x 1.3 x 2.0 1[alpha]


 -/-


 91 mo


 Alive without
recurrence
2


 48


 5.6 x 4.8


 T3aN1bM0, IIIa

 Extended


 3.5 x 3.0 x 3.2 Well-circumscribed
tumor with cyst

 1.8 (large)

 0


 -/-


 74 mo


 Alive without
recurrence
3


 63


 9.0 x 8.5


 T3aN1bM0, IIIa

 Modified


 6.5 x 5.9 x 4.0 Well-circumscribed
tumor with cyst

 4.0 x 2.9 x 2.0 1[alpha]


 -/-


 7 mo


 Alive without
recurrence
TNM, tumor-node-metastasis (classification system); n, lymph node metastasis; ER, estrogen receptor; PR, progesterone receptor; Extended, extended radical mastectomy; Modified, modified radical mastectomy.

Among the resected lymph nodes, a single node involved tumor cells in each of two cases, and no lymph node involvement was found in the other case. These lymph node involvements consisted exclusively of carcinomatous components; spindle cell components were not seen in these lymph nodes.


Figure 4. Immunoreactivity for keratin in the spindle cell component. Immunohistochemical examination of Case 1 (a) and Case 3 (b), performed with the ABC method..


Figure 5. Immunoreactivity for vimentin in the spindle cell component. Immunohistochemical examination of Case 1 (a) and Case 3 (b), performed with the ABC method.


Since formalin-fixed paraffin-embedded tissue blocks were available in Cases 1 and 3, immunohistochemical examination was performed in these two cases. Some spindle cells in these tumors were positive for keratin (Fig. 4) and vimentin (Fig. 5). Furthermore, desmosome-like junctional structures were electron-microscopically observed between the spindle cells in Case 3 (Fig. 6). These immunohistochemical and ultrastructural findings supported the probability that the spindle-shaped cells were of epithelial origin, suggesting the precise diagnosis of spindle cell carcinoma.

Discussion

Spindle cell carcinoma is a rare breast tumor. Its incidence has been reported as 0.2% (3) or less than 0.5% (4). All tumors of our three patients were elastically firm and circumscribed, with cystic formations. These findings are consistent with previous reports in which spindle cell tumors of the breast were described as grossly nodular, hard, and well-circumscribed, frequently with one or more cysts (3,5,6). Spindle cell tumors have also been reported as somewhat larger than other tumors (8). The tumor size ranged from 5.2 to 9.0 cm, defined as T3 according to the Japanese clinical TNM classification system (7), which is fundamentally the same as the TNM classification (UICC: classified 1972, confirmed 1978). A large and well-circumscribed tumor with gross cyst formation in the breast is strongly suggestive of spindle cell carcinoma.


Figure 6. Electron-micrograph of the tumor in Case 3. Desmosome-like junctional structure is observed between spindle cells.

Although spindle cell carcinoma has been characterized as sheets of spindle cells often containing squamous epithelial islands (6), its definition is still controversial. It has been synonymously described as squamous carcinoma with spindle metaplasia, pseudosarcoma, sarcomatoid carcinoma, and carcinosarcoma (5). Spindle cell carcinoma has frequently been included in the broader category of metaplastic carcinoma (5,6). Gershell and Katzenstein (6) proposed that spindle cell carcinoma should be separated from metaplastic carcinoma since the latter term includes a heterogeneous group of tumors of uncertain histogenesis. Indeed, two cases originally recorded as carcinosarcoma were excluded from this study because of their heterologous metaplastic features. Wargotz et al. (5) noted that spindle cell carcinoma included a dominant spindle cell component and in situ and/or ductal, lobular, squamous, or mixed infiltrating carcinoma that merged contiguously with the spindle cell component. Our three cases were completely consistent with this definition; both of them consisted of bundles of spindle cells concomitant with the carcinoma component, i.e. squamous islands (Case 3) or invasive ductal carcinoma (Cases 1 and 2).

Early investigators believed that carcinoma somehow induced the adjacent stroma to undergo a sarcomatoid proliferation (9). However, immunohistochemical studies have recently suggested that spindle cell components are likely to be derived not from stromal but from epithelial cells (4,5). In the present study, spindle cell components were positive for keratin as a marker for epithelial cells (10) and desmosome-like junctional structures were observed between spindle cells, suggesting that spindle cell components were derived from epithelial cells. The expression of both keratin and vimentin in a tumor, as demonstrated in this study, has been reported in spindle cell carcinoma (4,5). During the transformation from the epithelial shape to the spindle shape, mammary epithelial cells might acquire mesenchymal features and loose constitutive characteristics such as ER. Indeed, as presented here, spindle cell carcinoma of the breast has been found to be negative for ER (5,8).

Prognosis in spindle cell carcinoma has been reported as comparable to that of common breast carcinoma (6,8,11). Although our mean follow-up duration of 57 months is not sufficient to evaluate its prognosis, all of our patients have survived without recurrence to date. Since spindle cell carcinoma seems to grow expansively within its circumscribed boundary (3,5,6) and to exhibit a low incidence of lymph node metastasis (3,5, 8), its malignant potential is likely to be lower than expected from its tumor size.

In summary, spindle cell carcinoma of the breast is an uncommon tumor and it forms a well-circumscribed shape, frequently concomitant with cysts. Histologically, its dominant component consists of sheets of spindle-shaped cells and it includes contiguous carcinoma components. The expression level of ER and the incidence of lymph node metastasis tend to be low. Despite the sarcomatous features, immunohistochemical and ultrastructural examination reveals that spindle cells are likely to be derived from epithelial cells of mammary glands. Relatively favorable prognosis is expected in spindle cell

References

1. Someren A, Karcioglu Z, Clairmont A Jr. Polypoid spindle cell carcinoma (pleomorphic carcinoma). Oral Surg 1976;42:474-89.

2. Randall G, Alonso W, Ogura J. Spindle cell carcinoma (pseudosarcoma) of the larynx. Arch Otolaryngol 1975;101:63-6. MEDLINE Abstract

3. Kaufman MW, Marti JR, Gallager HS, Hoehn JL. Carcinoma of the breast with pseudosarcomatous metaplasia. Cancer 1984;53:1908-17. MEDLINE Abstract

4. Ellis IO, Bell J, Ronan JE, Elston CW, Blamey RW. Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast. J Pathol 1988;154:157-65. MEDLINE Abstract

5. Wargotz ES, Deos PH, Norris HJ. Metaplastic carcinomas of the breast. II. Spindle cell carcinoma. Hum Pathol 1989;20:732-40. MEDLINE Abstract

6. Gersell DJ, Katzenstein A-LA. Spindle cell carcinoma of the breast. A clinicopathologic and ultrastructural study. Hum Pathol 1981;12:550-61. MEDLINE Abstract

7. Japanese Breast Cancer Society. The general rules for clinical and pathological recording of breast cancer. Jpn J Surg 1984;19:612-36.

8. Bauer TW, Rostock RA, Eggleston JC, Baral E. Spindle cell carcinoma of the breast: four cases and review of the literature. Hum Pathol 1984;15:147-52. MEDLINE Abstract

9. Foulds L. A transplantable carcinoma of a domestic fowl, with a discussion of the histogenesis of mixed tumors. J Pathol Bacteriol 1937;44:1-18.

10. Osborn M, Weber K. Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. Lab Invest 1983;48:372-94. MEDLINE Abstract

11. Huvos AG, Lucas JC, Foote Jr. FW. Metaplastic breast carcinoma. Rare form of mammary cancer. N Y J Med 1973;73:1078-82. MEDLINE Abstract

Received May 8, 1996; accepted July 2, 1996
For reprints and all correspondence: Michio Maemura, Second Department of Surgery, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371, Japan
Abbreviations: ABC, avidin-biotin peroxidase complex; ER, estrogen receptor; PR, progesterone receptor; TNM, tumor-node-metastasis (classification system)

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