Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast.

Abstract: Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.

Key Words: collision tumor, breast carcinoma, breast MALT lymphoma

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Multiple primary malignant tumors have been reported with increasing frequency over the years. Synchronous occurrence of multiple neoplastic processes is less common. In an autopsy study reported by Lee et al, only 0.8% of all cancer patients were found to have multiple primary synchronous tumors. (1) The incidence of breast cancer was the second highest in the entire cancer series (5.5%) although its association with other primary tumors was the lowest (2%). (1) The relationship between breast cancer and lymphoproliferative disease is also unusual with an association rate of 1.5%. (2) We describe a case of a 53-year-old female with a collision tumor composed of breast carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma, invading each other and occurring as a single mass in the right breast. Lymphomas of the breast are uncommon and primary malignant lymphoma of the MALT type is exceptionally rare.

Case Report

A 53-year-old African-American female presented with a small palpable mass in the left breast. Mammography showed a 1.5 cm round mass which required additional imaging. Ultrasound demonstrated an irregular mass that was highly suggestive of malignancy. Using ultrasound guidance, four core biopsies were obtained which showed poorly differentiated infiltrating ductal carcinoma with heavy lymphocytic response. She subsequently underwent left breast lumpectomy and sentinel lymph node lymphadenectomy. Intraoperative frozen section analysis of the sentinel node did not demonstrate metastatic carcinoma, however, an atypical lymphoid pattern was noted. The subsequent pathologic evaluation confirmed a 2.5 cm stellate, poorly differentiated ductal carcinoma, grade 3 according to the Nottingham histologic classification. The carcinoma exhibited a solid growth pattern with no tubule formation and mitotic figures that were easily identified. The tumor cells were large with pleomorphic nuclei, prominent nucleoli and abundant cytoplasm (Fig. 1). Lymphovascular invasion was not identified. Confluent fields of lymphoma cells surrounded and infiltrated the invasive carcinoma (Fig. 2). The neoplastic lymphoid cells were intermediate in size with dense, slightly irregular nuclei and pale abundant cytoplasm, collectively referred to as marginal zone cells (Fig. 3). These cells invaded some of the malignant ductal epithelium forming lymphoepithelial lesions (Fig. 4). Immunohistochemistry demonstrated CD20 reactivity and lack of CD5, cyclin D1, CD23 and BCL6 expression by the population of lymphoid cells, indicating B-cell lineage and supported the diagnosis of MALT lymphoma. The sentinel lymph node showed excessive replacement by MALT lymphoma demonstrating similar immunophenotype based on immunohistochemistry. No metastatic carcinoma was found in the sentinel lymph node. Computed tomography of the chest and abdomen showed a sclerotic focus which was worrisome for metastatic disease, requiring additional imaging studies. Positive emission computed tomography and bone scans did not show evidence of abnormal areas to suggest disease activity from either tumor. Staging bone marrow biopsy and flow cytometry did not demonstrate involvement by lymphoma or carcinoma. CA 15-3 was within normal limits at 15.5 U/mL. A Port-A-Cath was placed and she was started on six cycles of CHOP therapy (cytoxan, Adriamycin, vincristine and prednisone) for the treatment of lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for her breast cancer. The patient tolerated her course of radiation and chemotherapy satisfactorily and was clinically stable.

Discussion

Lymphomas involving various organs including stomach, rectum and ovary have been reported as components of collision tumors. (6) Several cases of concomitant lymphoma and metastatic breast carcinoma in the lymph nodes have been previously described. (6-12,15) Our patient was diagnosed with concurrent mammary carcinoma and MALT lymphoma, presenting as collision tumor, infiltrating each other and occupying a single tumor in the same breast. Only a few cases similar to our patient's have been described in the literature. (13,14,15) In the case reported by Susnik et al, extensive involvement by lymphoma was demonstrated in the twenty-seven lymph nodes recovered, and one lymph node showed metastatic carcinoma. Staging bone marrow biopsy also showed involvement by B-cell lymphoma with no evidence of carcinoma. In our patient, metastatic carcinoma was not identified in the sentinel lymph node and bone marrow; lymphoma was not evident in the bone marrow as well. Rosen also cited a case of coexistent tubulolobular carcinoma and small cell lymphocytic lymphoma in the same breast. (13) In addition, collision between breast cancer and lymphoma around the primary breast cancer was reported by Wiernik et al. (15)

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Primary breast lymphomas are uncommon and represent 0.04% to 0.52% of all malignant breast neoplasms, 1.7% of extranodal non-Hodgkin lymphoma and 0.7% of all non-Hodgkin lymphoma. (3) Most lymphomas of the breast are high grade or large cell lymphomas. Low grade lymphomas including MALT lymphomas are far less common. (4) The incidence of MALT lymphomas among the breast lymphoma cases ranges from 8.5 to 35%. (5) It is an important subset of extranodal lymphoma that has distinct histologic and immunologic features and demonstrates an indolent clinical behavior with important therapeutic implications. (3)

There have been proposed mechanisms and factors or conditions that may play a role in the occurrence of synchronous breast carcinoma and lymphoma. Predisposing factors could be host related such as advanced age of the patients, exposure to common carcinogen, primary or cancer-related immunologic impairment, genetic predisposition to cancer or therapy-related factors inducing oncogenic effects and development of secondary neoplasms. (10) However, previous studies cited by Wiernik et al and the data presented by the authors demonstrated a relationship between breast cancer and non-Hodgkin lymphoma that is not therapy related. (15) Mechanisms involving the acquisition of MALT lymphoma have also been speculated including autoimmunity, hormonal influences or as a result of immune-mediated chronic inflammation. (3) Susnik et al suggested that the coexistent carcinoma acted as an antigenic stimulant which may have triggered the lymphomagenesis, a mechanism similar to the pathogenesis of acquired MALT lymphoma of the stomach as a result of the reaction to infection with Helicobacter pylori. (14) Recently, new evidence has suggested that human breast cancer and lymphoma may share a common etiologic agent involving mouse mammary tumor virus (MMTV). Several studies have detected the presence of MMTV in cancer tissues of patients with concurrent primary lymphoma and breast cancer, suggesting that the two neoplasms may have a common viral etiology. (15-17) Cotterchio et al suggested that this intriguing evidence warrants further investigation and that the possible role of viruses, such as MMTV, in the etiology of breast cancer and lymphoma is extremely important because of the great potential for preventive measures such as vaccines. (17) Factors influencing the coexistence of the two neoplastic processes in this particular case remain unknown. Simple coincidence however, should also be considered. (7)

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Conclusion

This case emphasizes that one should keep an open mind to the possibility of synchronous multiple primary neoplasms in patients with carcinoma. The importance of recognizing this is due to its therapeutic and prognostic implications; it will also prevent inaccurate staging and delay in the diagnosis of the coexistent tumor. In addition, the presence of carcinoma with marked lymphocytic infiltrate within the breast should raise suspicion of a low grade lymphoma such as MALT lymphoma. Understanding the histologic and clinical features of breast lymphomas and the use of ancillary studies including immunohistochemistry, flow cytometry and molecular cytogenetics should be considered for proper diagnosis and patient management.

References

1. Lee T, Myers RT, Scharyj M, et al. Multiple primary malignant tumors (MPMT): study of 68 autopsy cases (1963-1980). J Am Geriatr Soc 1982;30:744-752.

2. Herrmann JB. Lymphoproliferative disease secondary to breast cancer. NY State J Med 1971;711108-1111.

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4. Knowles DM. Neoplastic Hematopathology, 2nd ed. Philadelphia, Lippincot Williams & Wilkins, 2001.

5. Brogi E, Harris NL. Lymphomas of the breast: Pathology and clinical behavior. Semin Oncol 1999;26:357-364.

6. Allal AS, Weintraub J, et al. Concurrent interfollicular Hodgkin's disease and metastatic breast carcinoma in lymph nodes. Pathol Int 1996;46:787-790.

7. Stierer M, Rose HR, et al. Synchrony of malignant lymphoma and breast cancer. JAMA 1990;263:2922-2923.

8. Caraway NP, Wojcik EM, et al. Concomittant lymphoma and metastatic carcinoma in the lymph node: diagnosis by fine-needle aspiration biopsy in two cases. Diagn Cytopathol 1997;17:287-291.

9. Pandey U, Naraynan M, et al. Carcinoma metastasis to unexpected synchronous lymphoproliferative disorder: report of three cases and review of literature. J Clin Pathol 2003;56:970-971.

10. Luciana A, Stefano B, et al. Breast carcinoma metastatic to a lymphoma: report of a case with review of literature. Histopathology 1999;34:87-89.

11. Benoit L, Arnould L, et al. Concurrent lymphoma and metastatic breast carcinoma in the axillary, confounding sentinel lymph-node biopsy. Eur J Surg Oncol 2003;30:462-463.

12. Frey BM, Morant R, et al. Simultanes Auftreten von Mammakarzinom und malignem lymphom. Scweiz Med Wochenschr 1994;124:1010-1016.

13. Rosen PP. Rosen's Breast Pathology, 2nd ed. Philadelphia, Lippincot Williams & Wilkins, 2001.

14. Susnik B, Rowe JJ, et al. A unique collision tumor in breast invasive ductal carcinoma and mucosa-aaociated lymphoid tissue lymphoma. Arch Pathol Lab Med 2004;128:99-101.

15. Wiernik PH, Hu X, et al. Non-Hodgkin's lymphoma in women with breast cancer. Cancer J 2000;6:336-342.

16. Etkind P, Du J, et al. Mouse mammary tumor virus-loke ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient. Clin Cancer Res 2000;6:1273-1278.

17. Cotterchio M, Nadalin V, Sauer M. Human breast cander and lymphomas may share a common etiology involving mouse mamary tumour virus (MMTV). Med Hypotheses 2002;59:492-494.

Joanne M. Quilon, MD, Thomas A. Gaskin, MD, Arthur S. Ludwig, MD, and Catherine Alley

From the Baptist Medical Center, Birmingham, AL.

Reprint requests to Joanne M. Quilon, MD, Baptist Medical Center, 800 Montclair Road, Birmingham, AL 35213. Email: [e-mail]

Accepted June 8, 2005.

RELATED ARTICLE: Key Points

* The relationship between breast cancer and lymphoproliferative disease is unusual with an association rate of 1.5%.

* Primary breast lymphomas are uncommon and represent 0.04% to 0.52% of all breast malignant neoplasms.

* The incidence of MALT lymphomas among the breast lymphoma cases ranges from 8.5 to 35%.

* Among other factors implicated in the occurrence of synchronous breast carcinomas and lymphoma, mouse mammary tumor virus (MMTV) has recently been suggested to be a common etiologic agent of the two neoplasms.

* It is important to keep an open mind to the possibility of multiple primary neoplasms in patients with carcinoma.