Primary lymphoma of the breast. A clinicopathological study.

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     1  Primary Lymphoma of the BreastA Clinicopathological Study Dr Michelle De Padua Senior Consultant, Histopathology Apollo Hospitals Hyderabad, INDIA
     2  Introduction Primary Non Hodgkins Lymphoma of the breast is a rare disease. The proportion of lymphomas of all malignant tumours of the breast is in the range of 0.04-0.5%1-10. It can easily be confused for anaplastic carcinoma. Immunohistochemistry aids in differentiating between the two.
     3  Materials and Methods During a 2 year period, 2003 and 2004, we encountered 3 cases of NHL of the breast from among 199 cases of breast malignancies. All of them met the criteria for Primary breast lymphoma as proposed by Wiseman and Liao 1.Technically adequate material. 2. Close apposition of lymphoma and breast tissue. 3. Lack of previous extramammary lymphoma. 4. Documentation of breast as the primary clinical site. Metastatic workup which included USG abdomen, CT chest, and bone marrow biopsy, was negative in all cases. None of the cases had generalized lymphadenopathy. Wisemam C and Liao K. T. Primary lymphoma of breast. Cancer 1972; 29: 1705-1712.
     4  Case 1: 22 year old lactating lady presented with large mass (5x5cms) right breast. No axillary lymph nodes were palpable. Mammography revealed a large homogenous, lobulated, dense mass.
     5  FNAC revealed sheets of neoplastic cells with mildly pleomorphic hyperchromatic nuclei and scanty cytoplasm. It was reported as suggestive of an undifferentiated carcinoma, and possibility of a lymphoma was considered.
     6  Trucut biopsy was performed which revealed a tumour composed of sheets of neoplastic cells with round to oval vesicular nuclei , inconspicuous to prominent 2-3 nucleoli, irregular nuclear margins and scanty cytoplasm . Single cell as well as confluent necrosis was present with numerous mitotic figures.
     7  Immunohistochemistry with LCA and CD 20 was positive. CD3 and cytokeratin was negative. The features were that of NHL, diffuse large B cell type. LCA CD20
     8  Patient received 4 cycles of CHOP chemotherapy. There was a reduction in tumour size to 3x3 cms. Wide excision of the residual lump was performed 3 months after the primary diagnosis. The histology revealed tumour measuring 3x 2.2 cms, showing extensive coagulative necrosis with scanty foci of viable tumour. The surgical margins were negative. She received 2 more cycles of CHOP chemotherapy, followed by regional radiation. After a follow up of 28 months, she is well and disease free. Follow up CT chest, abdomen, and pelvis is normal.
     9  Case 2 46 year old lady with history of diabetes came with complaints of a left breast lump measuring 7X5cms. Mammography revealed a large opacity in the left breast with focal skin thickening and calcification. FNAC was reported as medullary carcinoma. Wedge biopsy of the lump was sent for frozen section which was reported as a malignant neoplasm. Sector mastectomy with axillary dissection was performed. Permanent sections revealed similar tumour as described in case 1. Immunohistochemistryconfirmed the diagnosis of of NHL, diffuse large B cell type. Twenty six axillary nodes were negative for tumour. She received 6 cycles of CHOP chemotherapy. She has been followed up for 33 months and is in complete remission.
     10  Case 3 51 year old lady presented with right breast lump measuring 3.5x3.5 cms. Fine needle aspiration cytology was suggestive of NHL Lumpectomy with axillary clearance was done. Final diagnosis after immunohistochemistry was NHL, diffuse large B cell type. She received 6 cycles of CHOP chemotherapy followed by regional radiation. She has been followed up for 28 months and is in complete remission.
     11  Discussion Our study confirms some of the previous observations in breast lymphoma and calls attention to the rarity of NHL lymphoma in the breast. Most cases of primary breast lymphomas present with palpable masses
     12  The right breast is involved in 2 cases and one case has a left sided involvement. Propensity for right breast involvement, intriguing but unexplained, has been reported in earlier series as well 1, 5, 7, 8. Mammographic appearance varies from discrete nodules with marginal irregularity, multiple thickenings, to diffuse increase in density and thickening of the skin.
     13  Problems in diagnosis Cytology may be misdiagnosed as carcinoma as was the case with one of our patients, where a diagnosis of medullary carcinoma was offered. Confirmed diagnosis on frozen section may not be possible 3,5,7 as was the problem in one of our cases.
     14  On permanent sections too, primary breast lymphomas can easily be mistaken for anaplastic carcinoma. Use of immunohistochemistry using a panel of antibodies that includes as a minimum, LCA, CD20, CD3, and an epithelial marker, is a great asset to the correct diagnosis, and should be mandatory if any doubt exists on morphology.
     15  In regard to histology, all our cases were classified as diffuse large B cell type. Diffuse large cell type is the most common in most series 1,4,5, 6, 7. Accurate preoperative diagnosis is of utmost importance since mastectomy can be avoided in these patients without affecting survival rate.
     16  Treatment There is no general agreement on the appropriate treatment of primary breast lymphoma. Schouten et al 14 reviewed treatment regimens and recommended an aggressive approach with multiple courses of combination chemotherapy following surgery or radiotherapy. In their series , Giardini et al5 reported best results with combination chemotherapy as primary therapy or after debulking surgery with or without regional radiation therapy.
     17  One of our cases had chemotherapy followed by surgical excision followed by completion chemotherapy and regional radiation. One case had surgery followed by chemotherapy alone. The third case had surgery followed by chemotherapy and radiotherapy. All of them are disease free with a median follow up of 29.6 months( 28 - 33 months).
     18  Prognosis Earlier reports by Wiseman and Liao 11 suggested a dismal prognosis for patients with only 3 out of 16 patients surviving for 5 years. However these patients were treated with only surgery or radiation and did not receive chemotherapy. Subsequent studies have shown a better prognosis 1,2 5 7
     19  More reliable data on prognosis and survival will depend on cooperative investigation of large number of patients studied by uniform treatment protocols and comparable histologic classification.
     20  Lin J. J, Farha G. J,and Taylor R.
     21  References 1. Lamovec J and Jancar J. Primary malignant lymphoma of the breast. Lymphoma of the Mucosa- Associated Lymphoid Tissue. Cancer 1987;60:3033-3041. 2. Ribrag V, Bibeau F, El Weshi A, et al. Primary breast lymphoma: a report of 20 cases. British Journal of Haematology 2001;115:253-256. 3. Telesinghe P. U and Anthony P.P. Primary lymphoma of the breast. Histopathology 1985;9:297-307. 4. Domchek S.M, Hecht J.L, Fleming M.D, Pinkus G.S, and Canellos G.P. Lymphomas of the breast. Primary and secondary involvement. Cancer 2002; 94:6-13. 5. Giardini R, Piccolo C and Rilke F. Primary Non-Hodgkins lymphomas of the female breast. Cancer 1992; 69:725-735.
     22  6. Bobrow L.G , Richards M.A, Happerfield L. C, et al . Breast lymphomas: A clinicopathological review. Human Pathology 1993;24: 274-278. 7. Cohen P.L and Brooks J.J. Lymphomas of the breast. A clinicopathologic and immunohistochemical study of primary and secondary cases. Cancer 1991; 67: 1359-1369. 8. Mattia A.R, Ferry J. A and Harris N.L. Breast lymphoma. A B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue. The American Journal of Surgical Pathology 1993; 17:574-587. 9. Huber S, Vesely M, Medl M and Czembirek H. Low –grade mucosa – associated lymphoma of the breast: radiological- pathological correlation. Eur Radiol 2002; 12: 1093-1096.
     23  10. Kambouchner M, Godmer P,Guillevin L, Raphael M , Droz D and Martin A. Low grade marginal zone B cell lymphoma of the breast associated with localized amyloidosis and corpora amylacea in a woman with long standing primary Sjogren`s syndrome. Journal of clinical pathology 2003; 56: 74-77. 11. Wisemam C and Liao K. T. Primary lymphoma of breast. Cancer 1972; 29: 1705-1712, 12. Ferguson D.J.P. Intraepithelial lymphocytes and macrophages in the normal breast. Virchows Arch (A ) 1985; 407: 369-378. 13. De Souza L.J and Talvarkar G.V. Primary malignant lymphoma of the breast. Indian Journal of Cancer 1978: 15: 30-35. 14. Schouten J.J, Weese J.L and Carbone P.P. Lymphoma of the breast. Annals of Surgery 1981; 194: 749-753.
     24  Thank You