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CASE REPORT  
Year : 2015  |  Volume : 58  |  Issue : 2  |  Page : 238-240
Malignant granular cell tumor of the breast; literature review


1 Department of Histopathology, Fortis Hospital, Faridabad, Haryana, India
2 Department of Histopathology, SRL, Mumbai, Maharashtra, India

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Date of Web Publication17-Apr-2015
 

   Abstract 

Malignant granular cell tumor (MGCT) is rare tumors that comprise 1-2% of all granular cell tumors. They commonly arise on lower extremity, nuchal region, chest wall, gastrointestinal tract, head, and neck but very rarely in breast. We report a case of a MGCT of breast with review of literature. The patient had noticed a breast mass 4 years back which was operated, and wide local excision was done. The tumor was diagnosed as MGCT. The tumor fulfilled 3 of the 6 criteria of Fanburg-Smith et al. The patient received 8 cycles of chemotherapy thereafter with 4 cycles of antharacycline and 4 of taxanes. However, the tumor reoccurred 4 years after resection and grew rapidly. Contrast-enhanced computed tomography done showed a large lobulated breast mass with axillary lymph node metastasis. She underwent Modified Radical Mastectomy with axillary clearance. The histopathology this time also revealed similar malignant tumor. To the best of our knowledge, only 7 cases have been reported in indexed English literature occurring primarily in breast.

Keywords: Breast, granular cell tumor, malignant

How to cite this article:
Gupta N, Sanchety N, Verma PS, Verma G. Malignant granular cell tumor of the breast; literature review. Indian J Pathol Microbiol 2015;58:238-40

How to cite this URL:
Gupta N, Sanchety N, Verma PS, Verma G. Malignant granular cell tumor of the breast; literature review. Indian J Pathol Microbiol [serial online] 2015 [cited 2020 Feb 19];58:238-40. Available from: http://www.ijpmonline.org/text.asp?2015/58/2/238/155330



   Introduction Top


Malignant granular cell tumor (MGCT) is a rare, aggressive neural tumor that was first reported by Ravich et al. in 1945. MGCT accounts for 1-2% of all granular cell tumors. They occur at various sites most commonly on lower extremities. MGCTs have been shown to be of Schwann cell origin. The diagnostic histological criteria has been proposed by Fanburg-Smith et al., [1] although these criteria for malignancy are still debated among pathologists. Wide local excision with lymph node dissection remains the main modality of treatment. However, the role of systemic chemotherapy is still debated.


   Case Report Top


We report a case of a 63-year-old female. The patient had noticed a breast mass 4 years back for which was operated and wide local excision was done.

Wide local excision of the tumor was done, and histopathology revealed a MGCT. Tumor cells show pleomorphism and areas of necrosis. Tumor measuring 37 mm × 35 mm in left outer quadrant. The tumor cells were positive for S-100 immunostains and negative for estrogen receptor (ER), progesterone receptor (PR) and Her2neu.

The patient received 8 cycles of chemotherapy thereafter with 4 cycles of antharacycline and 4 of taxanes. However, the tumor reoccurred a year after resection and grew rapidly. Contrast-enhanced computed tomography done 4 years after resection showed a large lobulated soft tissue density mass in upper outer quadrant of breast parenchyma involving underlying pectoralis major and minor muscle (15.2 × 12.5 × 9.4) with axillary lymph node metastasis. She underwent Modified Radical Mastectomy with axillary clearance.

Grossly

Serial section of the Modified Radical Mastectomy specimen revealed a tumor mass that was tan brown and measures 10 cm × 9 cm × 4 cm [Figure 1]a. Totally, 19 lymph nodes were dissected out from axillary clearance.
Figure 1: (a) Gross showing tan whitish tumor mass (b) Micrograph showing diffuse sheets of granular cells (H and E, ×20)


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Microscopy

Morphology of sections taken from the recurrent tumor mass were similar to the primary neoplasm composed of cells arranged in lobules and sheets having round to oval vesicular nuclei, prominent nucleoli and abundant granular eosinophilic cytoplasm [Figure 1]b. Individual cell necrosis and spindling of cells noted [Figure 2]b. Neoplastic cells are seen infiltrating the muscularis fibers [Figure 2]c.
Figure 2: Metastatic tumor deposit in lymph node (H and E, ×20) (b) Area of necrosis in tumor mass (H and E, ×20) (c) Tumor cell infiltrating muscle (H and E, ×20) (d1) Immunohistochemistry (IHC) for SMA negative, (d2) IHC GCDFP-negative, (d3) IHC S-100 diffusely positive and (d4) IHC Ki 67-0-1%


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Intracytoplasmic eosinphilic globules noted. They were not seen in primary neoplasm.

Immunohistochemistry done shows diffuse positivity of tumor cells to S-100 [Figure 2]d3 and negative for PanCK, CK7, Desmin, SMA [Figure 2]d1 and GCDFP [Figure 2]d2. Ki 67 index was 0-1% [Figure 2]d4. 10/19 lymph nodes show metastatic tumor deposits with extracapsular spread [Figure 2]a. Lymph vascular emboli and perineural invasion were also identified.


   Discussion and Review of Literature Top


Malignant granular cell tumor is a rare, aggressive neural tumor that was first reported by Ravich et al. in 1945. They represent only 1-2% of all granular cell tumors, accounting for <100 reported cases till date in indexed English literature.

Common on soft tissue of lower extremity. Other sites include gastrointestinal tract, urinary bladder, larynx, head and neck, vulva and very rarely in breast. [2],[3],[4],[5],[6],[7]

MGCT like benign tumors show female predominance (70%), with presentation usually in the fifth decade of life

Malignant granular cell tumor differs from benign counterpart in following clinical features:

  1. Longer clinical duration with sudden rapid growth
  2. Larger size on presentation (median size of 4-5.0 cm, as compared to benign tumors, which in most cases are <3 cm.)
  3. Often involves a history of local recurrence.
  4. Frequent localization to the lower limbs unlike benign granular cell tumors, which commonly occur in the head, neck, and tongue.


Most cases present as large mass varying in size from 4 to 20 cm slightly fleshy, firm, yellowish to tan brownish in color with foci of hemorrhage and degeneration Microscopically tumor shows sheets of polygonal cells with round hyperchromatic nuclei and abundant periodic-acid Schiff D positive eosinophilic cytoplasm. The tumor cells display features of malignancy.

Histological Criteria of Malignancy was first proposed by Fanburg-Smith et al. [1] They proposed 6 histologic criteria for the diagnosis of atypical and MGCTs, including necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses/10 high-power fields at ×200 magnification), high nuclear-to-cytoplasmic ratio, and pleomorphism.

Neoplasm's that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign.

Wang et al. has proposed a modification of above criterion as mitotic count (>5/50 HPF instead of >2/10 HPF) in 2004.

Immunohistochemistry tumor cells are positive for S-100, Ki-67 and p53 and negative for ER, PR, Her2neu, GCDFP and PanCK.

Electron micrograph showing intracytoplasmic, dense, membrane-bound lysosomes typical of granular cell tumor. Features are not helpful in distinguishing between benign and malignant lesions.

The origin of granular cell tumors is uncertain. Initially, it was thought that they arise from skeletal muscle, fibroblastic, histiocytic, or undifferentiated mesenchymal cell origin. More recently, based on the evidence that monoclonal antibody KP-1, which recognizes the lysosome-associated glycoprotein CD68, reacts positively with schwannomas and granular cell tumors; it is believed that these tumors arise from Schwann's cells. Also, granular cell tumors cytoplasmically stain for S-100 protein are closely associated with nerves and are often present in distal nerve trunks. All these features support a Schwann's cell origin.

Treatment comprises of wide local excision and regional lymph node dissection

Ordonez reviewed 41 cases of MGCT in the literature, most of which were treated with wide local excision and found a 59% recurrence rate. [8]

It is advisable to follow-up these patients annually to rule out late recurrences.

Radiation and chemotherapy are not advised because of the tumor's high degree of resistance. [9]

Prognosis is poor in patients with MGCT, with frequent metastasis (>50% overall) and 30-50% mortality over 3 years in two case series. [10]

Tumors typically spread via lymphatic and hematogenous routes to the lungs, liver, lymph nodes and bones.

Malignant granular cell tumor of breast

Malignant granular cell tumor of the breast can be primary or secondary. Primary MGCT is very rare with only 6 cases reported in indexed English literature till date [2],[3],[4],[5],[6],[7] [Table 1]. Most of these cases were unilateral and were described in females with a single case report in the male patient. Age of patient ranged from 46 to 79 years. Most of these patients present with a painless enlarging breast mass mostly in upper outer quadrant. Follow-up of the patient was available from 7 months to 9 years. Of the 6 patients, 3 died at 7, 12 and 34 months, and 2 did not have any reoccurrence. Wide local excision is the treatment of choice. However; follow-up of these patients is advisable annually to rule out late recurrences.
Table 1: Review of lietarature on malignant granular cell tumor of breast


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Role of adjuvant radiation and chemotherapy is still debatable.

 
   References Top

1.
Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG. Malignant granular cell tumor of soft tissue: Diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol 1998;22:779-94.  Back to cited text no. 1
    
2.
Crawford ES, De Bakey ME. Granular-cell myoblastoma; two unusual cases. Cancer 1953;6:786-9.  Back to cited text no. 2
    
3.
Kirschner H. On a case of malignant degeneration of myoblasticmyoma of the breast. Bruns Beitr Klin Chir 1962;204:87-94.  Back to cited text no. 3
    
4.
DeMay RM, Kay S. Granular cell tumor of the breast. Pathol Annu 1984;19:121-48.  Back to cited text no. 4
    
5.
Khansur T, Balducci L, Tavassoli M. Granular cell tumor. Clinical spectrum of the benign and malignant entity. Cancer 1987;60:220-2.  Back to cited text no. 5
    
6.
Chetty R, Kalan MR. Malignant granular cell tumor of the breast. J Surg Oncol 1992;49:135-7.  Back to cited text no. 6
    
7.
Akahane K, Kato K, Ogiso S, Sakaguchi K, Hashimoto M, Ishikawa A, et al. Malignant granular cell tumor of the breast: Case report and literature review. Breast Cancer 2012; doi: 10.1007/s12282-012-0362-1.  Back to cited text no. 7
    
8.
Ordóñez NG. Granular cell tumor: A review and update. Adv Anat Pathol 1999;6:186-203.  Back to cited text no. 8
    
9.
Lack EE, Worsham GF, Callihan MD, Crawford BE, Klappenbach S, Rowden G, et al. Granular cell tumor: A clinicopathologic study of 110 patients. J Surg Oncol 1980;13:301-16.  Back to cited text no. 9
    
10.
Thunold S, Von Eyben FE, Maehle B. Malignant granular cell tumour of the neck: Immunohistochemical and ultrastructural studies of a case. Histopathology 1989;14:655-7.  Back to cited text no. 10
    

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Correspondence Address:
Dr. Nalini Gupta
C6/18 Arr Dee City IInd Floor, Sector 52, Gurgoan - 122 001, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.155330

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