Saudi Journal of Medicine and Medical Sciences

CASE REPORT
Year
: 2014  |  Volume : 2  |  Issue : 2  |  Page : 120--122

Granulomatous reaction associated with breast carcinoma: A report of two cases


Timor Alalshee1, Tahira Hamed2, Sheikh M Shafi1,  
1 Department of Surgery, Specialized Surgical Unit, Makkah, Saudi Arabia
2 Department of Pathology, King Abdullah Medical City, Makkah, Saudi Arabia

Correspondence Address:
Timor Alalshee
Department of Surgery, Specialized Surgical Unit, King Abdullah Medical City, Makkah
Saudi Arabia

Abstract

The presence of a granulomatous reaction in association with a breast carcinoma is a rare phenomenon. We present two cases of breast carcinoma, invasive ductal and invasive lobular carcinoma in which a non-caseating granulomatous response was present within the stroma of the breast carcinoma, followed by a discussion of its pathogenesis and practical significance.



How to cite this article:
Alalshee T, Hamed T, Shafi SM. Granulomatous reaction associated with breast carcinoma: A report of two cases.Saudi J Med Med Sci 2014;2:120-122


How to cite this URL:
Alalshee T, Hamed T, Shafi SM. Granulomatous reaction associated with breast carcinoma: A report of two cases. Saudi J Med Med Sci [serial online] 2014 [cited 2021 Feb 27 ];2:120-122
Available from: https://www.sjmms.net/text.asp?2014/2/2/120/137010


Full Text

 INTRODUCTION



Granulomatous inflammation is considered to be an immune mechanism against infections or certain non-neoplastic conditions. Intratumoral granulomas and granulomas in lymph nodes draining breast carcinomas have been reported previously. However a granulomatous response in the lymph nodes draining cancers is unusual. Such granulomas may sometimes show tumor cells in their center. The exact cause of this phenomenon is not known, but an immunologic reaction to tumor antigens has been suggested. However, in regions where the incidence of tuberculosis (TB) is high, it is sometimes difficult to distinguish between a concomitant TB and a non-specific granulomatous response especially if there is an association with focal necrosis. In this article, we present two cases of breast carcinoma in which a non-caseating granulomatous response was present within the stroma of the breast carcinoma followed by a discussion of its pathogenesis and practical significance.

 Case Reports



Case 1

The first case is about a 55-year-old female native of Yemen presented to our breast oncology clinic with a mass in the right breast. She had a past history of colon cancer for which she was treated with colectomy and chemotherapy 4 years ago. The tru-cut biopsy of the mass showed a grade 2 infiltrating ductal carcinoma. She later on underwent breast conserving surgery in the form of the right breast lumpectomy and sentinel lymph node biopsy. The right lumpectomy specimen showed a 1.0 cm size grade 2 infiltrating ductal carcinoma. Lymphovascular invasion was negative. All margins were negative for malignancy. In addition, multiple non-caseating granulomas were noted in the tumor stroma [Figure 1]. Some of these granulomas revealed concentrically laminated microcalcifications in the giant cells. The sentinel lymph nodes sent for intra-operative frozen section were negative for metastasis, but all of the nodes showed non-caseating granulomas. These granulomas were composed of plump epithelioid cells and Langhan-type giant cells without evident necrosis. Ziehl-Neelsen (ZN), periodic acid-Schiff (PAS) and gomori methenamine silver (GMS) stains were negative for mycobacterium and fungus. All routine serological tests and extensive work-up of the patient were negative for infectious disease.{Figure 1}

Case 2

The second case is a 45-year-old Saudi female who presented with 1 year history of the right breast swelling. She gave a history of the recent increase in size of the breast and appearance of a right axillary lump. The tru-cut biopsy of the lump showed invasive lobular carcinoma with the presence of multiple non-caseating granulomas in the tumor stroma [Figure 2]. Immunohistochemistry showed CK AE1/AE3 and CK7 positive and E-Cadherin negative scattered tumor cells. Tumor cells were positive for estrogen and progesterone receptors and negative for Her-2 by immunohistochemistry. Later on, the patient underwent right modified radical mastectomy and axillary clearance. The mastectomy specimen showed a 6.0 cm size invasive lobular carcinoma with positive lympho-vascular invasion. All margins were negative. A similar granulomatous stromal reaction composed of plump epithelioid cells and Langhan and foreign body type giant cells was noted. Nineteen out of 19 lymph nodes were positive for metastatic carcinoma with focal extracapsular extension. In addition, all 19 lymph nodes revealed non-caseating granulomas associated with metastasis [Figure 3]. PAS and ZN stains were negative for organisms. There was no evidence of either localized or widespread infectious disease. All serological tests were negative for infectious disease.{Figure 2}{Figure 3}

 DISCUSSION



The occurrence of granulomatous response within the stroma of breast carcinoma is a rare and unusual phenomenon. [1],[2] The presence of sarcoid-type granulomas in lymph nodes draining carcinomas, including breast carcinomas, was first reported in detail by Gorton and Linell. In the specific context of breast carcinoma, Oberman [3] reported three cases of epithelioid granulomas within the stroma adjacent to invasive carcinomas of the breast, but without involvement of axillary nodes. [12] However, despite the rarity of these cases, granulomatous inflammation has been described in association of micro-invasive breast carcinoma and in relation to microscopic foci of colonic carcinoma within perivascular mesenteric fat. [4],[5] It has been frequently reported in a variety of other malignancies including, Hodgkin's lymphoma, non-Hodgkin's lymphoma, [6] testicular seminoma, ovarian dysgerminoma, nasopharyngeal, hepatocellular and renal carcinomas. [7],[8] Garanulomatous reaction is also seen in lymph nodes draining a tumor with or without the presence of metastasis. [9],[10],[11] In a study by Hall et al., they suggested that the local granulomatous response is a reaction to the presence of necrotic and poorly viable tumor and the granulomas in nearby lymph nodes may be a response to tumor derived debris. [6]

These granulomatous reactions are considered to be the result of T-cell mediated immune response (type IV hypersensitivity reaction) to the various tumor antigens either locally or in draining lymph nodes, or an idiopathic foreign body reaction to the necrotic zones in the tumor. [2],[3],[12] An abnormal immunological response, a type IV autoimmune reaction to tumor antigens and an unusual morphological variant have all been postulated as pathogenic mechanisms, but they have not been thought to be associated with or related to tumor necrosis. Although Rosen refers to the possibility that "traces of fibrinoid necrosis may be found in cellular lesions" and despite the single case described by Bδssler and Birke in which epithelioid granulomas with central fibrinoid necrosis occurred, the presence of prominent necrobiotic granulomas in breast cancer appears to be rare. [12] Morphologically these can lead to sarcoid like non-caseating epitheioid granulomas or necrobiotic palisading granulomas. The non-caseating granulomas consist of plump epithelioid histiocytes and few Langhan-type giant cells without evident necrosis. The necrobiotic palisading granulomas consist of eosinophilic, amorphous fibrinoid-like necrotic centers surrounded by palisaded histiocytes and occasional Langhan-type giant cells. [12],[13]

Finally, since the detection of a lobular carcinoma may sometimes be missed in standard hematoxylin and eosin stained sections of tiny needle biopsies, the diagnosis of cancer should always be considered and excluded whenever a granulomatous reaction is seen in a needle biopsy of the breast. The role of immunohistochemistry and special stains is important in this context.

 CONCLUSION



The presence of granulomatous reaction is an unusual tissue response to breast carcinoma. It usually raises the possibility of a systemic or local granulomatous disease as these patients may be immunocompromised due to the neoplastic process or chemotherapy. The special stains for microorganisms (ZN, PAS, GMS) and work-up of the patient is essential to rule out systemic and local granulomatous disease.

The detection of a lobular carcinoma may sometimes be missed in standard hematoxylin and eosin stained sections of tiny needle biopsies, therefore, the diagnosis of cancer should always be considered and excluded whenever a granulomatous reaction is seen in a needle biopsy of the breast. The role of immunohistochemistry and special stains is important in this context.

References

1Alujević A, Jurić G, Separović V, Kruslin B. Invasive breast carcinoma with granulomatous stromal response. Zentralbl Gynakol 1997;119:343-5.
2Santini D, Pasquinelli G, Alberghini M, Martinelli GN, Taffurelli M. Invasive breast carcinoma with granulomatous response and deposition of unusual amyloid. J Clin Pathol 1992;45:885-8.
3Oberman HA. Invasive carcinoma of the breast with granulomatous response. Am J Clin Pathol 1987;88:718-21.
4Coyne J, Haboubi NY. Micro-invasive breast carcinoma with granulomatous stromal response. Histopathology 1992;20:184-5.
5Coyne JD. Colonic carcinoma with granulomatous (sarcoid) reaction. J Clin Pathol 2002;55:708-9.
6Hall PA, Kingston J, Stansfeld AG. Extensive necrosis in malignant lymphoma with granulomatous reaction mimicking tuberculosis. Histopathology 1988;13:339-46.
7Gregorie HB Jr, Othersen HB Jr, Moore MP Jr. The significance of sarcoid-like lesions in association with malignant neoplasms. Am J Surg 1962;104:577-86.
8Tomimatsu H, Kojiro M, Nakashima T. Epithelioid granulomas associated with hepatocellular carcinoma. Arch Pathol Lab Med 1982;106:538-9.
9Gorton G, Linell F. Malignant tumours and sarcoid reactions in regional lymph nodes. Acta radiol 1957;47:381-92.
10Sethi S, Carter D. Breast carcinoma associated with necrotic granulomas in axillary lymph nodes. Ann Diagn Pathol 1998;2:370-6.
11Bhatia A, Kumar Y, Kathpalia AS. Granulomatous inflammation in lymph nodes draining cancer: a coincidence or a significant association. Int J Med Med Sci 2009;1:13-6.
12Coyne JD. Necrobiotic palisading granulomas associated with breast carcinoma. J Clin Pathol 2005;58:1290-3.
13Bässler R, Birke F. Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigations. Virchows Arch A Pathol Anat Histopathol 1988;412:231-9.