Abstract
OBJECTIVE To explore the clinico-pathological characteristics, diagnosis, treatment, and prognosis factors for primary breast malignant lymphoma (PBL).
METHODS The clinical data from 21 cases of PBL were retrospectively analysed.
RESULTS There were 19 females and 2 males with a median age of 37 years. All cases had diffuse non-Hodgkin lymphoma from B-cell lineage. The overall 5-year survival rate was 62.50% for the whole group and 81.82% for stage I and II diseases.
CONCLUSION The prognosis of PBL is related to the stage and treatment modality. Operation combined with chemoradiotherapy is the best treatment method. Local resection should be the first surgical treatment.
keywords
Primary breast malignant lymphoma (PBL) is a rare, malignant lymphoma which primarily occurs in the extra-nodular organs. It usually has a high malignancy and a poor prognosis, [1] but some scholars think its prognosis is better than breast cancer. [2] From August 1993 to October 2002, we received and treated 21 patients with PBL. In this report we reviewed the relative literature and with our study retrospectively analyzed its clinico-pathological characteristics, diagnosis, treatment and prognosis.
Materials and Methods
General data
The 21 PBL patients, included 19 females and 2 males, aged from 22 to 74 years with a median age of 37 years. The sites of the lesions were the left breast in 11 patients and the right in 10. Their initial symptom was an indolent mass in 20 patients with the whole breast swelling in one patient. The diameter of the tumors varied from 1.0 to 12.5 cm (≤ 5.0 cm 16 patients, > 5.0 cm 5 patients, mean diameter 3.5 cm). The masses had a texture of moderate hardness, without tenderness and a clear or obscure margin. Eleven out of 21 patients had swelling in their axillary lymphatic nodes in the involved lateral, and 4 had the concomitant symptoms of fever, night sweats and loss of body weight etc.
Diagnostic method
Of all the patients, one was diagnosed definitely by fine needle aspiration cytology, two by biopsy of the lymph nodes, and the remaining 18 by pathological results of the resected tumors. Intraoperatively 6 patients were examined by frozen sections but none received a confirmed diagnosis.
Treatment method
Of the 21 cases, 19 received surgical therapy which included 6 radical resections and 13 regional resections. Because of severe complications the remaining two did not receive an operation. All of the 21 cases underwent chemotherapy, 17 received CHOP, 3 BACOP and 1 COPP. Thirteen patients received radiotherapy. The combined therapy was: radical resection plus chemotherapy 3 cases, radical therapy plus chemo-radiotherapy 3 cases, regional resection plus chemotherapy 5 cases, regional resection plus chemo-radiotherapy 8 cases and chemotherapy plus radiotherapy 2 cases.
All the data were analysed by SPSS and the survival rate was calculated by the Kaplan-Meire method.
Pathological results
All of the 21 cases had a definite diagnosis of PBL (diffuse Hodgkin's B-cell lymphoma) by the Department of Pathology in our hospital. The results of the immunohistochemical examination for 13 cases were as follows: CK (negative); AE1/AE3 (negative); LCA (negative); CD20, CD45RA, CD79α(positive); CD45RO (negative). According to the Ann Arbor staging criteria for malignant lymphoma, 10 cases were in stage I, 6 in stage II and 5 in stage IV.
Follow-up
All cases were followed-up until December 2003. Out of the 10 cases in stage I, 5 cases survived for 5 years without recurrence; one for 2 years without recurrence; two for 1 year without recurrence; one had a cardiac tumor 6 months after the first therapy, and after remission from chemotherapy the patient received an autotransplantation of stem cells. He survived for 21 months from the time of diagnosis to December 2003; 1 patient survived for 19 months and died of multi-lymph node metastases in the kidneys and retroperitoneum.
Three of the 6 patients in stage II survived for 5 years without recurrence; 1 case survived for 3 years without recurrence; 1 case had a recurrence in the contralateral breast 3 years after treatment and died with bone metastases 4 months later; 1 case survived for 4.5 years and died with lung metastasis.
For the 5 cases in stage IV, 1 case survived for 13 months and ultimately died of respiratory and circulatory failure; 1 case survived for 16 months and died with liver and retroperitoneal multi-lymph node metastases; 1 case survived for 23 months and died with mediastinal metastasis.
Results
In this study, the overall 5-year survival rate of these patients was 62.5% (± 12.10%). For patients in stage I and II it was 81.82% (± 11.63%), and for patients in stage IV the 5-year survival was 20.00% (± 17.89%).
DISCUSSION
Clinical manifestation of PBL
The reported incidence of PBL has varied from 0.04% to 0.53% of all primary breast malignant tumors, and from 0.38% to 0.70% of all malignant lymphoma. The patient's median age was 34 years as reported by Wu and Hu [3] and 63 years by Aozasa et al.[4] In our study, the incidence of PBL accounted for 0.245% of primary breast malignant tumors and 0.494% of malignant lymphoma over a corresponding period with a median age of 37 years. The most often involved site was the right breast,[5,6] but there was no significant difference between the right and left side in our study. The initial symptom of these patients was a painless, mass that enlarged quichly in the breast. A minority of cases had accompanying symptoms such as fever, night sweats, loss of the body weight etc, without characteristic clinical manifestations.
Diagnosis for PBL
The diagnostic criteria for PBL proposed by Wiseman are:(1)The lymphatic tissue coexisted in the mass with the mammary gland tissue; (2)No history of malignant extramammary lymphoma; (3) The side initially involved was the mammary gland followed by involvement of the homolateral axillary lymph nodes; (4) The cancerous cells infiltrated into the mammary lobe and duct with the mammary epithelium showing no malignant appearance.
Presently there is no effective diagnostic method before conducting an operation, no tumor markers for reference and no specific imaging features upon radiological examination. [7] Fine needle aspiration cytology has limited value for diagnosis, and only 1 case in our study acquired confirmed diagnosis by this method. In order to aquire a confirmed diagnosis of PBL, a pathological examination should be performed; however in our report of cases intraoperative frozen sections had little benefit for the diagnosis and none of the 6 cases were diagnosed definitely by this method. The traditional pathological examination using a paraffin section is relatively more accurate and immunohistochemistry effectively helped the differential diagnosis. For the patients who received a definite diagnosis, a routine chest X-ray, abdominal B-mode ultrasound and a peripheral blood test should be performed. Patients with a suspicious diagnosis should receive a gastrointestinal tract examination and bone marrow biopsy in order to exclude general lymphoma and extra-medullary leukemic infiltration.
Treatment of PBL
At present theis is no unanimous opinion for PBL chemotherapy. Surgical operations for PBL use 2 methods: radical resection and regional resection. Some scholars think that radical resection is best for controlling local recurrence and finding axillary lymph node metastases. In our study, 8 cases in stage I and II underwent regional resection and then received radiotherapy and chemotherapy. None of these patients had a local recurrence. Although axillary metastases were helpful for I and II staging, the cases in stage I and II usually received the same radio-chemotherapy scheme, so a definite presence of axillary metastasis failed to direct the treatment. If the patients who received routine 6~8 courses of chemotherapy postoperatively acquired clinical cure, they would be reexamined regularly.
Compared to CHOP, recently the new chemotherapeutic schemes (such as M-BACOD, ProMACE etc.) had no significant difference in effectiveness and survival period. Because CHOP has the lowest incidence of lethal toxicity, it should still be the standardized chemotherapeutic scheme. [8] Chemotherapy also produced some efficacy for the patients in a late stage. One stage-IV patient received general chemotherapy for 5 years and survived without a tumor. Radiotherapy was always performed after chemotherapy or between the courses of chemotherapy. The regions treated consisted of the involved breast, ipsilateral axillary fossa and supraclavicular region at a dose of 40~50 Gy. Some researchers reported that patients who did not receive radiotherapy after chemotherapy or if the radiotherapeutic dose was less than 35 Gy, they would often have a local recurrence a few months after treatment. For patients receiving radiotherapy with a dose of more than 45 Gy, none of them had a recurrence.[3] In our study, 10 cases in stage I and II received postoperative chemotherapy plus radiotherapy (40~50 Gy) and sufferred no recurrence. However 3 of the 6 cases who received postoperative chemotherapy alone had a recurrence.
Prognosis of PBL
From the literature, the 5-year survival rate of PBL patients was 18.7% as reported by Zeng and Meng [9] and 77.0% by Wu and Hu[3] (most of the patients were in stage I and II ). As the majority of our patients were also in stage I and II, the total 5-year survival rate was 62.5% in our study. Our results of survival corresponded with the literature [6] in that the survival period of the PBL patients related to the tumor staging and the mode of treatment. One study indicated that age was one of the important factors influencing the prognosis, but we failed to find a similar result.[5]
In our opinion from the results discussed, a radical resection compared to a regional resection did not have an obvious value for survival of PBL patients. Considering the severe trauma for the patients' body and mental distress as well as the delay required for the following chemotherapy and radiotherapy, using a regional resection to achieve a confirmed diagnosis was an appropriate choice. In cases where a regional resection fails to remove a large mass, a radical resection should be performed to ease the tumor load. Being a systemic disease, PBL should be treated by general chemotherapy after a definite diagnosis is made to assure curing of the disease. If regional radiotherapy is also performed, it can prevent both neoplastic recurrence and metastasis, with patients surviving for a long time.
- Received January 14, 2005.
- Accepted April 28, 2005.
- Copyright © 2005 by Tianjin Medical University Cancer Institute & Hospital and Springer
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