Post-transplant lymphoproliferative disease of the breast

Clinical History

The patient, who had undergone a heart transplant at age 13, was admitted to hospital at age 23 with high fever and lymphadenopathy. Serology was positive for Epstein-Barr virus.

Imaging Findings

The patient was born with situs inversus, asplenia (Fig. 1), atrial septal defect and transposition of the great arteries. A heart transplant was performed at the age of 13 because of end-stage congestive heart failure and was followed by 10 years of almost normal development.

At the age of 23 the patient was hospitalised with high fever and lymphadenopathy. Serology was positive for Epstein-Barr virus. Bone marrow biopsy showed "...polymorphous post-transplantation lymphoproliferative disease (PTLD), Hodgkin's-like, EBV positive." Excisional biopsy of a 1cm right axillary lymph node performed at the same time showed "...destroyed architecture by a diffuse polymorphous lymphoproliferative process composed of small, medium and large immunoblasts, compatible with PTLD...with Hodgkin's-like features."

The patient was hospitalised on and off for chemotherapy, febrile neutropaenia, bacteraemia, candidaemia and resistance to chemotherapy during the next 18 months. At the age of 25 she was hospitalised again to perform homologous bone marrow transplantation. Routine tests before the transplant revealed asymmetric and lumpy breasts with the left one being larger than the right and having a centrally located palpable mass. An additional right breast tail mass was combined with a, most probably lymphatic, mass in the right axilla.

Mammography showed extremely dense breasts that were somewhat nodular. The left breast was larger and denser, and the right breast showed an asymmetric density in its tail. No focal lesion could be identified and the axillary lymph nodes were not visualised (Fig. 2).

Ultrasound examination of the breasts showed two enlarged lymph nodes in the right axilla, one of them having blurred borders and a rich blood supply. Within the left breast, the palpable mass was identified as a lobular, heterogeneous mass having rich blood supply and a heterogeneous posterior enhancement/shadow zone (Fig. 3).

Whole body computed tomography showed lymph node enlargement, involving the right axilla and the mesenteric root (Fig. 4). The CT also showed the asymmetric, extremely dense breasts and the asymmetric density on the right breast tail (Fig. 5). Pneumatosis intestinalis, bowel loops with thickened walls and some infiltration of the mesenteric fat, all common graft vs. host reactions, were also present in the lower abdomen (Fig. 6).

Persistent candidaemia and E. coli bacteraemia complicated the clinical picture. Attempts at stabilising the disease and performing the transplant failed, and the patient died on the tenth day of hospitalisation.

Discussion

PTLD represents an uncontrolled lymphoid expansion. Usually it is the result of Epstein-Barr virus (EBV)-induced B cell lymphoproliferation that is unopposed by the suppressed T-cell system. The frequency of PTLD is around 2%. Diagnostic features of PTLD differ from those of lymphoma in immunocompetent patients. They may resemble lymphomas in acquired immunodeficiency syndrome (AIDS) or congenital T-cell immunodeficiency. Characteristics of PTLD are extranodal involvement and a variable response to treatment. Three significant risk factors should be taken into account: allograft type transplant, EBV infection and immunosuppressive treatments. The disease usually occurs within the first year after transplantation.

PTLD may be focal or diffuse and can affect almost any organ system and even the allograft. The clinical manifestations are: nonspecific symptoms of fever and malaise, an infectious mononucleosis-like syndrome and palpable lymphadenopathy, or symptoms referable to solid or hollow organ involvement with consequent dysfunction. The extent of disease can be minimal at first, progressing rapidly or waxing and waning over several weeks, invariably disseminating widely if proper therapeutic measures are not taken. Definitive diagnosis requires tissue biopsy.

Treating PTLD implies reduction in immunosuppression, control of EBV replication, immunotherapy, and conventional antineoplastic therapy. Disease regression in response to a reduction in immunosuppression is a unique diagnostic feature of PTLD and distinguishes this condition from other malignant diseases. Patients should be closely monitored for allograft rejection. Surgical resection might control limited disease. The only way that might improve the response to therapy is early diagnosis.

Imaging studies in PTLD are aimed at assessing the degree of lymph node involvement, revealing infection and bronchiolitis obliterans and evaluation of the extent of abnormality. Follow-up, response to treatment as well as guidance of biopsy are also tasks of diagnostic imaging studies.

The mammographic picture of PTLD is unspecific and similar to lymphoma of any type, primary or metastatic. Although mammography does not play any role in the early detection of PTLD, it should be known that breasts might be involved by the disease and should be treated within the context of the systemic disease.

Differential Diagnosis List

Final Diagnosis

Post-transplant lymphoproliferative disease – breast involvement

URL:	https://www.eurorad.org/case/1712
DOI:	10.1594/EURORAD/CASE.1712
ISSN:	1563-4086