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Colocalized granular cell tumor and infiltrating ductal carcinoma of the breast: a case report and review of the literature.

Granular cell tumor (GCT) is a relatively uncommon lesion, which most often affects the tongue, skin, and subcutaneous tissue, although it may occur at any body site. (1) Granular cell tumor was first described by Abrikossoff (2) in 1926 as granular cell myoblastoma, assuming a myogenic origin. However, other investigators have since proposed histiocytic, fibroblastic, myoepithelial, and neuronal origins. (3)

Approximately 6% of GCTs occur in the breast. (4,5) Granular cell tumor in association with ductal carcinoma of the breast has been reported in the contralateral (4) and ipsilateral (5) breast. When present in the ipsilateral breast, GCT was 2.0 Cm from a previous lumpectomy site for infiltrating ductal carcinoma. (5) We describe a case of granular cell tumor of the breast colocalized with an in situ and infiltrating ductal carcinoma in a lumpectomy specimen. To our knowledge, this is the first case to be reported with such an association and may raise new questions about the significance of pseudoepitheliomatous hyperplasia commonly seen with GCTs at various body sites.

REPORT OF A CASE

A 57-year-old African-American woman with a previous medical history of colon cancer, but no family history of breast cancer, presented in July 2000 with a lump in her right breast, which had been palpable for approximately 2 years. Results of a recent prior mammogram had been negative. Breast examination revealed an approximately 1.5-cm, rounded, nontender mass in the upper inner quadrant. There was no lymphadenopathy. Fine-needle aspiration yielded no fluid. She underwent a right breast excisional biopsy. Following the pathology findings, she underwent a right axillary nodal dissection, which revealed 12 lymph nodes, all negative for neoplasia. She received postoperative radiation therapy to the right breast and was free of disease on follow-up examination (9 months).

PATHOLOGIC FINDINGS

A 5 x 4 x 1.4-cm fragment of lobulated, yellow, fibro-fatty breast tissue was received for examination. The cut surface revealed a poorly circumscribed, firm tumor nodule measuring 1.1 cm in greatest dimension. Microscopically, 2 histologically distinct lesions were seen in the same tumor Some sections showed areas composed purely of a well-differentiated invasive ductal carcinoma, while others showed a GCT (Figure 1, C). In 1 section, the 2 tumors appeared to merge and infiltrate each other (Figure 1, A). Microscopically, the GCT (Figure 1, C) consisted of sheets and cords of polygonal cells with round small nuclei and abundant eosinophilic, granular cytoplasm; the GCT measured 1.1 cm. The invasive ductal carcinoma was well differentiated and had histologic and nuclear grades of I/III, and measured 1.0 cm. Admixed with the invasive ductal carcinoma was ductal carcinoma in situ of solid and cribriform types with low nuclear grade (Figure 1, B). Rare microcalcifications were seen associated with the invasive ductal carcinoma but not with ductal carcinoma in situ or GCT. The rest of the breast tissue showed fibrocystic changes. Immunohistochemical studies (Table), after reviewing the appropriate controls, showed the invasive ductal carcinoma to be positive for keratin (Figure 2, A) and estrogen receptors and negative for progesterone receptors and HER-2/neu protein. The GCT was positive for S100 protein and negative for keratin (Figure 2, B), estrogen receptor, progesterone receptor, and HER-2/neu protein.

[FIGURES 1-2 OMITTED]

COMMENT

Abrikossoff (2) first described the entity of GCT of the tongue in 1926 as granular cell myoblastoma, claiming a myogenic origin. Investigators now favor a neural origin, and the tumor is thought to be derived from Schwann cells, as supported by positivity for S100 protein and neuron-specific enolase immunohistochemically. (5) Ultrastructural examination of 1 of the 8 cases studied by Mittal and True (6) showed evidence of origin of the granules from the cell membrane by infolding in a way similar to that of myelin formation around axons, except that folding occurs inside rather than outside the cells. These granules are then autophagocytosed (autodigested by lysosomes), resulting in the characteristic ultrastructural appearance of the granules seen in the cytoplasm of GCTs.

Granular cell tumor occurs in various organs, most commonly the tongue, which accounts for nearly 30% of all GCTs. (7) Affected patients are predominantly in their fourth to sixth decades, and children are rarely affected. (3,8) In general, GCTs are twice as common in women as in men. (3) They typically present in premenopausal women, although they can occur at any age from adolescence onward. (4) In a study by Billeret, (8) GCT was twice as common in men as in women, and the most common location was the skin, followed by the esophagus. Only 6% to 8% of GCTs occur in the breast, with a ratio of 1 to every 1000 breast cancers. Previously, most cases of GCT were symptomatic; however, with improved mammography, more asymptomatic cases are being detected. (4) In the breast, GCT occurs most commonly in the upper inner quadrant (as in the current case) and is less common in the lower outer quadrant. This pattern appears to parallel the distribution of the supraclavicular nerve that supplies sensory innervation to the breast skin. (5) Due to the infiltrative growth pattern of GCT, it may clinically and mammographically simulate invasive carcinoma. (9) Histologically, GCT has distinct features and is characterized by infiltrating sheets and cords of polygonal bland cells with abundant eosinophilic granular cytoplasm, which stains positively for periodic acid--Schiff and S100 protein. (4) Although GCTs are almost always benign, malignant cases with lymph node metastases have been reported. (10)

Granular cell tumor of the breast is not commonly associated with any other breast tumors. (4) Mulcare (11) reported a case of GCT of the breast as an incidental finding in a radical mastectomy specimen for carcinoma in a 49-year-old woman. In another case, also reported by Mulcare, a carcinoma developed in the same breast 5 years after the removal of a GCT Gordon et al (12) reported a case of GCT developing at the site of mastectomy for a breast carcinoma 15 years previously. Tai et al (4) described a case of simultaneous invasive carcinoma in one breast and GCT in the contralateral breast. Recently, Tran et al (5) reported a case involving a 74-year-old woman, in which a GCT was found 2 cm from a previous lumpectomy site of an infiltrating ductal carcinoma. To our knowledge, the case we describe is the first in which a GCT and an infiltrating ductal carcinoma were colocalized in the same radio-graphically detected breast lesion. The differential diagnosis includes GCT involving an area of adenosis; however, the presence of unequivocal ductal carcinoma in situ confirms malignancy.

At other sites, the epithelium overlying GCTs exhibits pseudoepitheliomatous hyperplasia in 10% of cases, which can be misinterpreted as squamous cell carcinoma. (3) Rarely, however, cases of true squamous cell carcinoma in association with GCTs have been described. Carcinomas associated with GCTs in other organs have also been described, including squamous cell carcinoma of the esophagus, adenocarcinoma of the stomach, adenocarcinoma and small cell undifferentiated carcinoma of the lung, and vulvar carcinoma in situ. (3) These reports, along with the case described here, raise 2 important questions for pathologists: (1) is there a causal relationship between GCT and carcinomas, or is this colocalization a mere coincidence, as concluded by others (9); and (2) is pseudoepitheliomatous hyperplasia when present at other sites with GCT not a well-differentiated squamous cell carcinoma in many instances? In an attempt to address the latter issue, morphometric studies were performed by van der Wal et al, (7) which produced inconclusive results. Fortunately, in most cases with both GCT and pseudoepitheliomatous hyperplasia, the latter is superficial and can be excised completely.

The predominance of GCTs in premenopausal women has prompted a suggestion of a causal relationship with high estrogen levels. (4) In our case, however, the tumor developed in a postmenopausal woman and was negative for estrogen and progesterone receptors. These findings are in agreement with other observations in the literature. (4)

To summarize, we report a case of GCT colocalized with an infiltrating ductal carcinoma of the breast in a postmenopausal woman.
Immunohistochemical Stains

 Antibody Manufacturer Dilution

Cytokeratin Boehringer-Mannheim Diagnostics,
 Indianapolis, Ind 1:400
S100 Dako Corporation, Mountain View,
 Calif 1:300
Estrogen receptor Ventana Medical Systems Inc, Tucson,
 Ariz Prediluted
Progesterone receptor Ventana Prediluted
HER-2/neu Novocastra Laboratories Ltd,
 Newcastle Upon Tyne, United
 Kingdom 1:80


References

(1.) Williams HK, Williams DM. Oral granular cell tumor: a histological and immunocytochemical study. J Oral Pathol Med. 1997;26:164-169.

(2.) Abrikossoff A. Uber Myome, Ausgehend von der quergestreiften, willkurlichen Muskulatur. Virchows Arch Pathol Anat. 1926;260:215-233.

(3.) Said-Al-Naief N, Brandwein M, Lawson W, Gordon R, Lumerman H. Synchronous lingual granular cell tumor and squamous carcinoma: a case report and review of the literature. Arch Otolaryngol Head Neck Surg. 1997;123:543-547.

(4.) Tai G, D'Costa H, Lee D, Watkins RM, Jones P. Case report: coincident granular cell tumour of the breast with invasive ductal carcinoma. Br J Radiol. 1995;68:1034-1036.

(5.) Tran TA, Kallakury BV, Carter J, Wolf BC, Ross JS. Coexistence of granular cell tumor and ipsilateral infiltrating ductal carcinoma of the breast. South Med J. 1997;90:1149-1151.

(6.) Mittal KR, True LD. Origin of granules in granular cell tumor: intracellular myelin formation with autodigestion. Arch Pathol Lab Med. 1988;112:302-303.

(7.) van der Wal N, Baak JPA, Schipper NW, van der Waal I. Morphometric study of pseudoepitheliomatous hyperplasia in granular cell tumors of the tongue. J Oral Pathol Med. 1989;18:8-10.

(8.) Billeret LV. La tumeur a cellules granuleuses: epidemiologie de 263 cas. Clin Exp Pathol. 1999;47:26-30.

(9.) Vos LD, Tjon A, Tham RT, Vroegindeweij D, Vrints LW. Granular cell tumor of the breast: mammographic and histologic correlation. Eur J Radiol. 1994;19: 56-59.

(10.) Uzaoru I, Firfer B, Ray V, Hubbard-Shepard M, Rhee H. Malignant granular cell tumor. Arch Pathol Lab Med. 1992;116:206-208.

(11.) Mulcare R. Granular cell myoblastoma of the breast. Ann Surg. 1968;168: 262-268.

(12.) Gordon AB, Fisher C, Palmer B, Greening WP. Granular cell tumour of the breast. Eur J Surg Oncol. 1985;11:269-273.

Accepted for publication October 1, 2001.

From the Departments of Pathology (Drs AI-Ahmadie, Yassin, and Mutema) and Surgery (Dr Hasselgren), University of Cincinnati Medical Center, Cincinnati, Ohio.

Reprints: George Mutema, MD, PhD, Departments of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, 231 Bethesda Ave, PO Box 670529, Cincinnati, OH 45267-0529 (e-mail: mutemagk@uc.edu).
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Article Details
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Author:Al-Ahmadie, Hikmat; Hasselgren, Per-Olof; Yassin, Rawia; Mutema, George
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Jun 1, 2002
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