April 2007

Fig.3

Fig.4

Fig.5

Diagnosis: Recurrent diffuse large B-cell lymphoma with secondary cutaneous involvement

Histopathology: A punch biopsy was taken of one of the skin lesions on the right thigh showing a pan dermal infiltrate of large cells staining positively with CD79a.

The original lymph node biopsy showed sheets of large malignant cells effacing the lymph node architecture with high grade histology demonstrating numerous mitotic figures and apoptotic debris. Flow cytometry demonstrated a kappa restricted population of large CD19 and CD20 positive B-cells. Cytoplasmic CD79a is expressed and with further testing a positive expression of BCL-2 was determined.

Imaging: CT scan: anterior chest wall mass, right sided pleural effusion, right posterior rib fractures, pleural based soft tissue mass, single enlarged lymph node in the right external iliac chain.
MRI: large mass in right nasal cavity and soft tissues of the right face and maxillary sinus with destruction of local osseous structures, lesion in left scalp, non-specific changes in brain parenchyma.

Treatment and course: Having already completed nine cycles of chemotherapy and a stem cell transplant prior to this relapse the patient was determined not to be a candidate for further chemotherapy and was offered palliative radiation for her right anterior chest wall mass and right hip mass. Ultimately her functional status continued to decline and the patient was discharged to hospice care following a three week hospital course.

Discussion: Cutaneous B-cell lymphoma may represent either primary disease or secondary spread of systemic disease. Secondary spread is more common, as an estimated 6-10% of all patients with B-cell lymphoma have skin manifestations during their disease course. Incidence of primary B-cell cutaneous lymphoma is estimated to be 0.2 per 100,000 people.

Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma and is the most common histologic subtype, representing 30% of all NHLs with an estimated incidence of 3 cases per 100,000 adults. Risk factors include age (median age 64 years), family history of lymphoma, HIV infection, immune suppression, and prior radiation or chemotherapy. Prognosis, determined by the International Prognostic Index (IPI), is based on tumor stage, serum LDH, number of extranodal disease sites, performance status, and age. Five-year survival rates are approximately 73% in low risk patients and 26% in high risk patients. Secondary cutaneous involvement of a systemic NHL implies Stage IV disease and a worse prognosis. Generally solitary lesions are more consistent with primary cutaneous disease, and widespread lesions suggest secondary cutaneous involvement. Other poor prognostic signs include lesions on the leg, and expression of BCL-2, both of which were present in this patient.

Treatment aggressiveness is based on prognosis. Advanced stage disease is usually treated with CHOP chemotherapy, as more aggressive regimens have not demonstrated improved remission and are associated with higher toxicity. The addition of rituximab in CD20+ disease has also been demonstrated to improve survival. The approach to recurrent or refractory lymphoma consists of salvage chemotherapy and radiation. Autologous stem cell transplantation can be performed in refractory disease only in patients who demonstrate a response to chemotherapy.

References:

References:
1. Blay, J et al. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: Analysis of the PARMA trial. Parma Group. Blood 1998; 92:3562.
2. Feugier, P et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma. Journal of Clinical Oncology 2005; 23:4117.
3. Shipp, MA et al. International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury. Journal of Clinical Oncology 1999; 17:423.
4. Willemze, R et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105:3768
5. James WD et al. Andrews' Diseases of the Skin. Tenth Edition. Elsevier Inc. 2006.

This case is presented by Drs Bonnie Lee, Cheryl Gray, Amy Cheng, and Kimberly Crone.