Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Indurated Breast During Lactation Guillermo Solano-López, MD; María José Concha-Garzón, MD; Javier Sánchez-Pérez, MD
A
B
Figure. A, Enlargement and induration of both breasts. B, Histopathologic specimen from the breast (hematoxylin-eosin, original magnification ×40).
A healthy woman in her 40s, lactating, 5 months post partum, presented with a 1-month history of enlargement and induration of both breasts (Figure, A). A skin biopsy specimen from the breast was obtained (Figure, B). She was initially diagnosed with mastitis and received several courses of antibiotics for 2 months without improvement. Subsequently she presented with back pain, paresthesias, shooting pain in the mandibular region, and diplopia. All of these conditions improved under treatment with oral corticosteroids, but the breast enlargement continued. Laboratory test results highlighted a hemoglobin level of 7.6 g/dL and a platelet count of 80 000/μL. (To convert hemoglobin to grams per liter, multiply by 10; to convert platelets to number of cells × 109/L, multiply by 1.0.)
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Acute lymphoblastic leukemia of the breast B. Breast implant foreign body reaction C. Severe postpartum mastitis D. Burkitt lymphoma of the breast
(Reprinted) JAMA Dermatology February 2015 Volume 151, Number 2
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
223
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis D. Burkitt lymphoma of the breast
Microscopic Findings and Clinical Course A skin biopsy of the breast showed extensive infiltration of the superficial and deep dermis by monomorphic medium-sized cells with scant cytoplasm and rounded vesicular nucleus with fine chromatin and occasional irregularity of the nuclear membrane and numerous mitoses imparting the appearance of a starry sky (Figure, B). The immunophenotype showed CD45+, CD20+, CD10+, bcl-6+, CD43+, TDT−, bcl-2−, CD34−, and EBER− with Ki-67 proportion greater than 95%, all findings compatible with Burkitt lymphoma (BL). The molecular study showed the c-Myc translocation, and cytogenetic analysis showed 8:14 translocation. The patient also demonstrated pleural fluid, cerebrospinal fluid, and bone marrow involvement. Systemic and intrathecal chemotherapy was started, followed rapidly by improvement of the breast induration and the supradiaphragmatic and infradiaphragmatic involvement. At last follow-up, the patient was undergoing further cycles of chemotherapy.
Discussion Primary lymphomas of the breast are uncommon tumors. There are 2 different clinicopathologic groups: one occurs in young women bilaterally and is often associated with pregnancy or lactation: a Burkitt-type lymphoma. The other clinicopathologic group affects a broad age range, but primarily older woman, and is usually a B-cell non-Hodgkin lymphoma with clinical features identical to carcinoma of the breast. This second type presents as a unilateral mass and has a better prognosis than BL.1,2 Burkitt lymphoma is a predominantly extranodal aggressive form of non-Hodgkin lymphoma. It has a predilection for the mandibular area, gastrointestinal tract, kidneys, breast, and ovaries. Bone marARTICLE INFORMATION Author Affiliations: Department of Dermatology, Hospital Universitario de La Princesa, Madrid, Spain. Corresponding Author: Guillermo Enrique SolanoLópez, MD, C/ Diego de León, 62, 28006 Madrid, Spain ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: December 10, 2014. doi:10.1001/jamadermatol.2014.2821. Conflict of Interest Disclosures: None reported.
row and the peripheral blood are affected in advanced stages. There is a translocation of the c-Myc gene on chromosome 8 with the heavy or light chain of the immunoglobulin on chromosome 2, 14, or 22.3 Burkitt lymphoma is classified into 3 types: sporadic, endemic, or associated with human immunodeficiency virus. Skin involvement is very rare.4,5 Negahban et al6 found a total of 47 cases of BL with breast involvement in the literature. Of these 47 cases, 14 occurred during the lactational period, and 13 occurred during pregnancy. The times of occurrence of the other 20 cases were not defined. Of these 47 cases, 32 occurred bilaterally. The survival rates for primary BL of the breast in the lactation period and in pregnancy were 14.3% and 30.8%, respectively. Most of the lactation-associated BLs (92.8%) were stage I, whereas those occurring in pregnancy were mainly stage IV (61.5%). If the onset of BL is in the breast, then it is often bilateral and massive, and it is usually associated with pregnancy or lactation, which might suggest hormonal influences on its pathogenesis.6 There are no randomized clinical trials for adult BL to guide therapy. Treatment is based on small series. CODOX-M-IVAC chemotherapy (cyclophosphamide, vincristine, doxorubicin, highdose methotrexate-ifosfamide, etoposide, high-dose cytarabine, and intrathecal methotrexate) and the CALGB 9251 regimen7 are the most frequently cited in the literature. Radical surgery should be avoided.1 The present case is interesting because the diagnosis was reached mostly from a dermatologic evaluation. The patient had been treated previously for mastitis without any response for 2 months. The feature of BL with bilateral breast enlargement and induration during the peripartum period is very characteristic. Any pregnant or lactating women with severe or progressive bilateral breast enlargement unresponsive to anti-inflammatory and antibiotic treatment must be evaluated to rule out BL.
Additional Contributions: We thank M. Adrados, MD, Department of Pathology, Hospital Universitario de La Princesa, Madrid, Spain, for helping with the diagnosis and providing the pathologic image. REFERENCES
5. Fuhrmann TL, Ignatovich YV, Pentland A. Cutaneous metastatic disease: Burkitt lymphoma. J Am Acad Dermatol. 2011;64(6):1196-1197.
1. Savvari P, Matsouka C, Barbaroussi D, et al. Burkitt’s lymphoma in pregnancy with bilateral breast involvement: case report with review of the literature. Onkologie. 2010;33(8-9):461-464.
6. Negahban S, Ahmadi N, Oryan A, et al. Primary bilateral Burkitt lymphoma of the lactating breast: a case report and review of the literature. Mol Diagn Ther. 2010;14(4):243-250.
2. Janbabai G, Kayedimajd S, Alian S, Naghshvar F, Rashidi M, Farazmandfar T. Bilateral breast swelling in a 23-year-old woman with Burkitt lymphoma. J Res Med Sci. 2012;17(12):1188-1191.
7. Rizzieri DA, Johnson JL, Byrd JC, et al; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014;165(1):102-111.
3. Miyoshi I, Yamamoto K, Saito T, Taguchi H. Burkitt lymphoma of the breast. Am J Hematol. 2006;81(2):147-148.
224
4. Schmitz R, Young RM, Ceribelli M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116-120.
JAMA Dermatology February 2015 Volume 151, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Indurated Breast During Lactation Guillermo Solano-López, MD; María José Concha-Garzón, MD; Javier Sánchez-Pérez, MD
A
B
Figure. A, Enlargement and induration of both breasts. B, Histopathologic specimen from the breast (hematoxylin-eosin, original magnification ×40).
A healthy woman in her 40s, lactating, 5 months post partum, presented with a 1-month history of enlargement and induration of both breasts (Figure, A). A skin biopsy specimen from the breast was obtained (Figure, B). She was initially diagnosed with mastitis and received several courses of antibiotics for 2 months without improvement. Subsequently she presented with back pain, paresthesias, shooting pain in the mandibular region, and diplopia. All of these conditions improved under treatment with oral corticosteroids, but the breast enlargement continued. Laboratory test results highlighted a hemoglobin level of 7.6 g/dL and a platelet count of 80 000/μL. (To convert hemoglobin to grams per liter, multiply by 10; to convert platelets to number of cells × 109/L, multiply by 1.0.)
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Acute lymphoblastic leukemia of the breast B. Breast implant foreign body reaction C. Severe postpartum mastitis D. Burkitt lymphoma of the breast
(Reprinted) JAMA Dermatology February 2015 Volume 151, Number 2
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
223
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis D. Burkitt lymphoma of the breast
Microscopic Findings and Clinical Course A skin biopsy of the breast showed extensive infiltration of the superficial and deep dermis by monomorphic medium-sized cells with scant cytoplasm and rounded vesicular nucleus with fine chromatin and occasional irregularity of the nuclear membrane and numerous mitoses imparting the appearance of a starry sky (Figure, B). The immunophenotype showed CD45+, CD20+, CD10+, bcl-6+, CD43+, TDT−, bcl-2−, CD34−, and EBER− with Ki-67 proportion greater than 95%, all findings compatible with Burkitt lymphoma (BL). The molecular study showed the c-Myc translocation, and cytogenetic analysis showed 8:14 translocation. The patient also demonstrated pleural fluid, cerebrospinal fluid, and bone marrow involvement. Systemic and intrathecal chemotherapy was started, followed rapidly by improvement of the breast induration and the supradiaphragmatic and infradiaphragmatic involvement. At last follow-up, the patient was undergoing further cycles of chemotherapy.
Discussion Primary lymphomas of the breast are uncommon tumors. There are 2 different clinicopathologic groups: one occurs in young women bilaterally and is often associated with pregnancy or lactation: a Burkitt-type lymphoma. The other clinicopathologic group affects a broad age range, but primarily older woman, and is usually a B-cell non-Hodgkin lymphoma with clinical features identical to carcinoma of the breast. This second type presents as a unilateral mass and has a better prognosis than BL.1,2 Burkitt lymphoma is a predominantly extranodal aggressive form of non-Hodgkin lymphoma. It has a predilection for the mandibular area, gastrointestinal tract, kidneys, breast, and ovaries. Bone marARTICLE INFORMATION Author Affiliations: Department of Dermatology, Hospital Universitario de La Princesa, Madrid, Spain. Corresponding Author: Guillermo Enrique SolanoLópez, MD, C/ Diego de León, 62, 28006 Madrid, Spain ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: December 10, 2014. doi:10.1001/jamadermatol.2014.2821. Conflict of Interest Disclosures: None reported.
row and the peripheral blood are affected in advanced stages. There is a translocation of the c-Myc gene on chromosome 8 with the heavy or light chain of the immunoglobulin on chromosome 2, 14, or 22.3 Burkitt lymphoma is classified into 3 types: sporadic, endemic, or associated with human immunodeficiency virus. Skin involvement is very rare.4,5 Negahban et al6 found a total of 47 cases of BL with breast involvement in the literature. Of these 47 cases, 14 occurred during the lactational period, and 13 occurred during pregnancy. The times of occurrence of the other 20 cases were not defined. Of these 47 cases, 32 occurred bilaterally. The survival rates for primary BL of the breast in the lactation period and in pregnancy were 14.3% and 30.8%, respectively. Most of the lactation-associated BLs (92.8%) were stage I, whereas those occurring in pregnancy were mainly stage IV (61.5%). If the onset of BL is in the breast, then it is often bilateral and massive, and it is usually associated with pregnancy or lactation, which might suggest hormonal influences on its pathogenesis.6 There are no randomized clinical trials for adult BL to guide therapy. Treatment is based on small series. CODOX-M-IVAC chemotherapy (cyclophosphamide, vincristine, doxorubicin, highdose methotrexate-ifosfamide, etoposide, high-dose cytarabine, and intrathecal methotrexate) and the CALGB 9251 regimen7 are the most frequently cited in the literature. Radical surgery should be avoided.1 The present case is interesting because the diagnosis was reached mostly from a dermatologic evaluation. The patient had been treated previously for mastitis without any response for 2 months. The feature of BL with bilateral breast enlargement and induration during the peripartum period is very characteristic. Any pregnant or lactating women with severe or progressive bilateral breast enlargement unresponsive to anti-inflammatory and antibiotic treatment must be evaluated to rule out BL.
Additional Contributions: We thank M. Adrados, MD, Department of Pathology, Hospital Universitario de La Princesa, Madrid, Spain, for helping with the diagnosis and providing the pathologic image. REFERENCES
5. Fuhrmann TL, Ignatovich YV, Pentland A. Cutaneous metastatic disease: Burkitt lymphoma. J Am Acad Dermatol. 2011;64(6):1196-1197.
1. Savvari P, Matsouka C, Barbaroussi D, et al. Burkitt’s lymphoma in pregnancy with bilateral breast involvement: case report with review of the literature. Onkologie. 2010;33(8-9):461-464.
6. Negahban S, Ahmadi N, Oryan A, et al. Primary bilateral Burkitt lymphoma of the lactating breast: a case report and review of the literature. Mol Diagn Ther. 2010;14(4):243-250.
2. Janbabai G, Kayedimajd S, Alian S, Naghshvar F, Rashidi M, Farazmandfar T. Bilateral breast swelling in a 23-year-old woman with Burkitt lymphoma. J Res Med Sci. 2012;17(12):1188-1191.
7. Rizzieri DA, Johnson JL, Byrd JC, et al; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014;165(1):102-111.
3. Miyoshi I, Yamamoto K, Saito T, Taguchi H. Burkitt lymphoma of the breast. Am J Hematol. 2006;81(2):147-148.
224
4. Schmitz R, Young RM, Ceribelli M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116-120.
JAMA Dermatology February 2015 Volume 151, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
jamadermatology.com
