A rare occurrence of primary T-cell lymphoma of the breast in pregnancy

To the Editor,

Primary T-cell lymphoma of the breast is a very rare clinical entity. We report herein an extremely rare case of primary T-cell lymphoma of the breast during pregnancy. A 24-year-old woman in the 7th month of her first pregnancy was admitted to our hospital with a three month history of progressive enlargement of her left breast and left axillary lymph nodes. She denied fever, night sweats or weight loss. Her past medical history was significant for Evans syndrome diagnosed five years earlier at our hospital. Although her hemolytic anemia responded well to steroid, thrombocytopenia was refractory to both steroid and intravenous immunoglobulin treatment. Eventually a complete response was achieved after subsequent splenectomy. The hematologic values remained normal during her regular follow-up. Her physical examination revealed a 6 × 8 cm, hard irregular mass in the upper outer quadrant of the left breast and ipsilateral enlarged axillary lymph nodes. No other enlarged peripheral lymph nodes were found. The hematologic and biochemical parameters were within normal limits. The peripheral blood smear examination was normal. An obstetrical ultrasonography showed a single viable intrauterine pregnancy of 27 weeks gestational age. Abdominal ultrasonograhy was normal. A core needle biopsy of the breast mass revealed diffuse infiltration of atypical lymphoid cells with hyperchromatic nuclei and scant cytoplasm. Immunohistochemically, the tumor cells were positive for vimentin, CD3 and leukocyte common antigen, and negative for CD4, CD8, CD10, CD20, CD30, S-100, terminal deoxynucleotidyl transferase, desmin and cytokeratin, which suggested T-cell lymphoma. A bone marrow biopsy showed normal hematopoietic cells. The patient started chemotherapy with standard-dose CHOP-21 regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone). We observed a dramatic tumor regression after the first cycle of the treatment, and she achieved a complete clinical response after the second cycle. Eight weeks after the initiation of chemotherapy, a cesarean section was performed, which yielded an apparently healthy male infant weighing 2450 g. After delivery, computed tomography (CT)-scans showed no evidence of disease spread. Four additional courses of chemotherapy were administered, after which the patient was reevaluated. Her physical examination and CT-scans and magnetic resonance imaging (MRI) of the brain were normal. Bilateral mammography and ultrasound showed benign findings. Seven months after the completion of chemotherapy she was hospitalized again because of fever, productive cough, and shortness of breath. On physical examination she was in moderate respiratory distress and chest radiography and CT-scan showed infiltrates in the right lower and right middle lobes. In a matter of hours, the patient developed hypoxemic respiratory failure that required mechanic ventilation. She was transferred to the intensive care unit and empirically treated with broad spectrum antibiotics and anti-fungal agents. She developed multiple organ failure and died 15 days after her admission. Before the appearance of this clinical picture she was still in clinical complete remission. Unfortunately, no autopsy could be performed.

Primary T-cell lymphoma of the breast has been reported rarely and the majority of reports in the international medical literature are case reports. The ages of reported patients range from 13 to 77 years [1,2]. Both breasts seem to be equally affected by the disease and bilateral involvement was observed in two patients [3,4]. Peripheral T-cell lymphoma unspecified is the most common subtype and accounting for about 50% of the cases.

The treatment modalities administered for these patients were homogeneous or not clearly defined. Therefore, it is difficult to make any definitive recommendation regarding the best possible treatment for this tumor. Our patient had locally advanced disease and received only chemotherapy with six cycles of CHOP. She survived without evidence of disease recurrence for more than one year. The follow-up time for our patient may not yet be long enough to conclude that chemotherapy alone is sufficient for patients with primary T-cell lymphoma of the breast who respond completely to therapy. Ariad et al. reported on two patients with primary T-cell breast lymphoma presented with locally advanced disease [5]. These patients were treated with CHOP alone, and showed no evidence of recurrence during 24 and 60 months of follow-up, respectively. Cohen et al. reported on a 35-year-old female presenting with stage IE disease [6]. After biopsy, this patient received eight cycles of CHOP chemotherapy. At 44 months, the patient suffered a recurrence in the subcutaneous tissue but remained alive with disease at 48 months. Bhele et al. described a case of a 26-year-old pregnant woman with bilateral peripheral T-cell breast lymphoma successfully treated with eight cycles of CHOP chemotherapy [3]. Kebudi et al. reported on a 35-year-old female patient with bilateral breast and axillary lymph node involvement by low grade T-cell lymphoma [4]. Complete response was achieved after four cycles of chemotherapy consisting of cyclophosphamide, epirubicin, vincristine and prednisolone. But, brain and lung involvement was detected seven months after the initial diagnosis, and the patient died three months after recurrence. Briggs et al. suggested that patients with early-stage low-grade disease can effectively treated by lumpectomy and radiation therapy [7]. However, we suppose that postoperative radiation alone is an inadequate treatment for this disease, as in B-cell lymphoma of the breast. The clinical course of a case reported by Kosaka et al. demonstrated that mastectomy and CHOP chemotherapy may be another reasonable option for the treatment of primary T-cell breast lymphoma [8].

It is well known that hematological autoimmune diseases may increase the risk of development of NHL. Evans syndrome is a rare hematological autoimmune disease characterized by the simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia in the absence of known underlying etiology. Michel et al. suggested that patients with Evans syndrome should be followed for associated with NHL and the risk of development NHL is especially high for patients over 50 years of age [9]. NHL can occur many years after the onset of Evans syndrome, as in our case. Michel et al. also reported a stage IV B-cell NHL occurred eight years after the first manifestation of Evans syndrome in one patient [9]. Our case suggested that the possible existence of a relationship between Evans syndrome and primary breast lymphoma.

In summary, the optimal approach to primary T-cell breast lymphoma management is unknown. We believe that some selected patients might be treated with chemotherapy only.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.