Diffuse large B-cell lymphoma associated with skin, muscle and cranial nerve involvement

ARTICLE

Extranodal lymphoma is not uncommon, but the lymphomatous involvement of distal nerves or muscles is rare [1-8]. In this report, we describe a case of diffuse large B-cell lymphoma, which first manifested itself as left facial hemiplegia and paresthesia due to the involvement of peripheral cranial nerves and facial muscle. This case suggests that diffuse large B-cell lymphoma must be considered as one of the important causes of peripheral cranial nerve palsies.

Case report

In May 1997, a 75-year-old Japanese male noticed muscle weakness in his left face. Over the next year this symptom gradually progressed, with paresthesia in his left face and diplopia in his right eye. He was referred to our hospital in July 1998, and a diagnosis of peripheral polyneuropathy of unknown aetiology was made. The diplopia was improved one month after the original diagnosis, but erythematous indurated plaques developed on his left cheek and nose (Fig. 1).

A skin biopsy from the plaque on his cheek showed dense infiltrates of large cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm in the dermis and subcutaneous tissue (Figs. 2A, B). The predominant cell resembled a centroblast. The majority of tumor cells were positive for antibodies to leukocyte common antigen, CD20, CD22, CD79a, and bcl-2, but negative for CD3, CD4, CD5, CD8, CD10, CD30, CD56, EBV encoded latent membrane protein-1 (LMP-1), and anti-IgM, IgD antibodies. Immunohistochemical staining for kappa and lambda light chain of immunoglobulins showed a restricted reactivity of the tumor cells for the immunoglobulin lambda light chain. Rearrangement of immunoglobulin heavy chain gene was detected in the infiltrated cells in the same specimen by Southern-blot analysis. A muscle biopsy from facial muscle in the area of erythematous plaque showed massive destruction of the muscle tissues by the lymphomatous infiltrates, and the residual muscle fibers enclosed the neoplastic lymphocytes (Fig. 3).

Major abnormalities on physical examination were restricted to the facial area. Facial hemiplegia and paresthesia were present in his left nose, upper lips and cheek. No abnormal findings were obvious on neurological examinations, including vision, visual fields, optic fundi, extraocular movements, taste and hearing. A facial nerve conduction study showed an extremely low amplitude of compound motor action potentials in the left orbicularis oculi muscle. No blink reflex with stimuli over the left supraorbital nerve was detected in the orbicularis oculi muscles.

Laboratory findings included: white blood-cell count 5,000/mul with 25.0% lymphocytes and 0.0% atypical lymphocytes, red blood-cell count 412 x 10⁴/mul, platelet count 18.1 x 10⁴/mul, erythrocyte sedimentation rate 12 mm/1 h; aspartate aminotransferase 9 U/L; alanine aminotransferase 11 U/L; alkaline phosphatase 105 U/L; serum creatine kinase 142 U/L; lactate-dehydrogenase 199 U/L; gammaglobulin 1.8 g/dl with IgG 1,449 mg/dl, IgM 85 mg/dl, and IgA 244 mg/dl. Rheumatoid factor was not detected. Anti-nuclear antibody titre was 40 with a diffuse pattern. Results of serum IgG antibody against Epstein-Barr viral capsid antigen (EB-VCA) and Epstein-Barr nuclear antigen (EBNA) were positive, with titres of 40 and 10, respectively, but IgM antibody against EB-VCA was negative. The remainder of the work-up, including serum test for syphilis and HTLV-1, were normal or negative. ⁶⁷Ga citrate scintigram showed marked accumulation in the left face. Magnetic resonance imaging (MRI) of the head showed thickening of skin and facial muscle in the left cheek and epithelium of paranasal sinus regions. There were no characteristic findings in bone marrow biopsy, chest X-ray or whole body CT scanning. In particular, there was no evidence of the enlargement of the liver, spleen and lymph nodes. We concluded that primary diffuse large B-cell lymphoma of the facial muscle in the left cheek may develop symptoms such as facial hemiplegia and paresthesia prior to cutaneous manifestations.

For treatment, the patient underwent a combined chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone. The skin lesions improved after the initial therapy. After the fifth therapy, the paresthesia subsided but the muscle weakness persisted in the left face. Although additional chemotherapy was administered with radiotherapy of 35 Gy applied to the area, the muscle weakness has never really improved.

Discussion

The presenting clinical feature of this patient was left facial hemiplegia and paresthesia. Electrodiagnostic study showed peripheral cranial nerve palsies, involving the left facial and trigeminal nerves. Various clinical investigations could not identify an obvious cause for these neuropathies. However, a skin biopsy from the facial plaque and the underlying muscle biopsy revealed the infiltration of diffuse large B-cell lymphoma. These findings led us to the conclusion that the facial hemiplegia and paresthesia were due to lymphomatous involvement in the cranial nerves and the facial muscles.

Peripheral neuropathy is an unusual complication of lymphoma [1-5]. The involvement of the peripheral nervous system (PNS) is predominant in proximal sites, including roots and plexi, and only a few cases have been reported with a complication of PNS in distal levels [1, 5]. In our case, the neurological findings suggested the invasion of lymphoma cells into both the facial and trigeminal nerves at the distal levels, although no histological examination was carried out.

Among the well-recognized extranodal presentations of lymphoma, the distinct muscular involvement of lymphoma is considered to be extremely rare [6-8]. In 2,147 Japanese autopsy cases of malignant lymphoma from 1976 to 1978, the frequency of muscle involvement was only 1.44% [6]. Muscle involvement of lymphoma can occur via metastatic spread and direct invasion from the affected adjacent tissue or from a primary extranodal lesion [7, 8]. In our case, the facial muscle weakness may be caused by the direct invasion of diffuse large B-cell lymphoma, because the massive lymphomatous infiltration was confirmed histologically in the adjacent dermis, subcutaneous tissue and muscles.

CONCLUSION

We conclude that diffuse large B-cell lymphoma may develop symptoms such as facial hemiplegia and paresthesia prior to cutaneous manifestations. Diffuse large B-cell lymphoma must be considered to be one of the important causes of palsies of cranial nerves at the peripheral level.

Article accepted on 15/2/00

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