Figure 59-1 A, Transverse paraffin section stained with Luxol fast blue/periodic acid–Schiff demonstrating injury neuroma. Transverse paraffin sections stained with hematoxylin and eosin (B) demonstrating perivascular epineurial inflammatory cells with reactivity for CD-20 (C) and PAX-5 (D).

The patient was treated with six cycles of rituximab and fludarabine and achieved a partial remission with minimal lymphadenopathy and no further deterioration in his neurologic disorder. The patient subsequently had progressive improvement in his weakness and sensory deficits. The right footdrop had improved. He continued to report reduced grip strength and numbness in the third and fourth digits bilaterally with contact allodynia, however these were improved. Examination demonstrated improvement in hand weakness bilaterally, with moderate deficits in the ulnar distribution bilaterally, and improvement in the right peroneal weakness. Ten months after completing therapy, the patient had streptococcal meningitis and subsequently Pneumocystis carinii pneumonia. He was then started on intravenous immunoglobulin for prevention of further infections. One year after completion of treatment with fludarabine and rituximab, he experienced deterioration of his peripheral neuropathy and was started on treatment with rituximab and cyclophosphamide. After four cycles, the patient demonstrated improvement in his neurologic deficits.

CONCLUSION

Although neuropathies can be the presenting manifestation or a complication of various lymphoproliferative diseases, neuropathy associated with CLL is rare. In the reported cases, compression and paraneoplastic manifestations due to monoclonal protein production are the putative causes of neuropathy. Direct neoplastic infiltration is uncommon, and a presentation of multiple mononeuropathies even less so.¹^–⁴ Créange and colleagues⁵ reported three cases of neuropathy in patients with CLL. The first patient presented with an acute demyelinating polyradiculoneuropathy with features of active demyelination and perivascular lymphocytic inflammation; the second patient presented with an axonal peroneal mononeuropathy with features of small vessel vasculitis on nerve biopsy; and the third patient presented with multiple mononeuropathies and muscle biopsy with small collections of lymphoid cells around small vessels and nerve biopsy demonstrating rare lymphocytes. Polymerase chain reaction analysis of immunoglobulin heavy chain gene showed clonal B-cell rearrangement in all biopsies.

In our patient, there was evidence of a microvasculitis with invasion of the blood vessel walls by lymphocytes. These lymphocytes demonstrated reactivity for CD-20, a B-cell marker, as well as PAX-5, a B-cell transcription factor and a specific marker of B lineage.⁶ This proved the microvasculitis was caused by the CLL. The extent of infiltration of the nerve by CLL cells suggested that these cells had an etiologic role in the neuropathy and was critical in deciding to treat the CLL. By hematologic criteria, the patient had intermediate stage CLL and did not meet the standard criteria for treatment of his disease. Because the neuropathy was proved to be secondary to CLL infiltration, the hematologist was convinced to initiate chemotherapy, which ultimately led to improvements in the patient’s neuropathy and resulting morbidity.

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