Primary lymphoma of the medial cutaneous nerve of the forearm: the first case in a pure sensory nerve of the upper limb

Abstract

Primary lymphoma of the peripheral nerve is very rare and occurs most frequently in sciatic nerves. We describe the first patient reported in literature with a primary lymphoma in a pure sensory peripheral nerve of the upper limb. A woman in her 40s, with painful swelling and dysaesthesias in her left forearm in the past 3 months, was presented at our unit. Clinical MRI and ultrasound findings revealed a lesion that showed signs of a peripheral nerve sheath tumour. After complete excision, morpho-pathological evaluation revealed a primary B-cell lymphoma. The patient underwent radiotherapy and at the last follow-up there were no signs of residual pathology. Peripheral neuropathy may be caused by a lymphoma involving the nerve. Hand surgeons have to distinguish primary lymphoma of the peripheral nerves from schwannoma for their different clinical behaviour.

Background

Lymphomas are malignant tumours arising from a malignant transformation of B lymphocytes or T lymphocytes. Primary lymphoma of the peripheral nerve (PLPN) is a condition with malignant lymphocytes infiltrating only peripheral nerves with no other sign of generalised lymphoma.¹ PLPNs are very rare and occur most frequently in sciatic nerves.² In hand surgery, benign nerve tumours are more common than malignant, but PLPNs are very rare malignant tumours mimicking peripheral nerve sheath tumours leading frequently to misdiagnosis in clinical practice. In literature, PLPNs of the upper limb are described only in six cases, three radial nerve,^3–5 one median nerve⁶ and two ulnar nerve cases,^{7 8} involving always a mixed nerve, that is, motor and sensory nerve.

In this article, we present the first case of a pure sensory nerve primary lymphoma involving the medial antebrachial cutaneous nerve in a 47-year-old woman.

Case presentation

A woman in her 40s, with no medical history, in good health, presented at our hand surgery unit reporting painful swelling and dysaesthesias in her left forearm in the past 3 months. On examination she showed no movement limitations but only sensory symptoms.

Investigations

Nerve ultrasound demonstrated increased cross-sectional areas of her medial antebrachial cutaneous nerve (figure 1). MRI depicted a delimited tumour in the subcutaneous tissue of the medial antebrachium, 7×3×3 cm in size (figure 2). Imaging did not support any specific diagnosis but appeared to be a schwannoma. Surgical exploration and excision were planned. During surgery, a tumour covering the medial head of triceps fascia and surrounding all nerve branches of the medial cutaneous nerve was found (figure 3). Complete excision of two nerve branches, which seemed infiltrated by the tumour, was performed (figure 4).

Figure 1.

US imaging. Complex cystic lesion with irregular margins measuring 43×18×20 mm, with marginal hyper-reflective structures not clearly recognisable as a lymph node hilum. Signs of hypervascularisation of the lesion are visible. The lesion adheres to the underlying muscle fascia.

Figure 2.

MRI in T1 (on the left) and STIR (on the right). Solid spindle-shaped lesion measuring 70×30×30 mm, in contact with the superficial subcutaneous adipose tissue and the deep vascular-nervous bundle.

Figure 3.

(A) Clinical findings of the mass. (B-C) Intraoperative findings. A medial longitudinal brachial incision revealed the tumour nestled on the septum intermusculare brachii medialis, surrounding and infiltrating the antebrachial medial cutaneous nerve branches sheaths (white arrows).

Figure 4.

(A) Complete tumour excision was performed, including two sensitive nerve branches which appeared in continuity with the tumour, asterisk indicates the septum intermusculare brachii medialis. (B) The underlying surface was cauterised in order to prevent recurrences as indicated by the white arrow. (C) Gross appearance and measurement of the tumour mass.

Histological examination revealed a 4.3 cm solid whitish polylobate lesion with fleshy appearance adherent to a 5.4 cm nervous trunk. H&E-stained sections (figure 5) of the lesion showed nervous fascicles infiltrated by large, pleomorphic, uncleaved, mitotically active lymphocytes with centroblastic appearance with few centrocytic elements; centroblasts were >15 per high power field. These cells showed a follicular pattern of growth and were delimited by fibrous septa. Neoplastic elements displayed a diffuse cytoplasmic immunostaining for CD20 and nuclear immunostaining for PAX5, indicating a B lymphocyte immunophenotype, and additionally CD10, BCL2 and BCL6 positivity. Proliferation was not oriented and Ki-67 immunostaining showed a proliferative index between 35% and 65%. CD23 +dendritic-follicular reticulum was completely exploded. These findings led us to a diagnosis of follicular lymphoma G3a. Neoplastic elements showed infiltration of the proximal resection margin of the nervous trunk, while the opposite margin was not involved. The patient was referred to the haematology department. Lymphocyte typing and bone marrow biopsy showed no signs of lymphomatous involvement. Cranial, cervical, thoracic and abdominal TC and PET-TC showed hypercaptation in homolateral axillary lymph nodes.

Figure 5.

H&E-stained sections show a dense proliferation of neoplastic large lymphocytes with a follicular pattern of growth delimited by fibrous septa (A, magnification 50×); neoplastic elements have a predominant centroblastic appearance and infiltrate nervous fascicles (B, C, magnification 400×). Lymphoid cells are diffusely and strongly positive for CD20 (D, magnification 200×) and BCL-2 (E, magnification 200×) with a proliferative rate detected with Ki-67 comprised between 35% and 65% (F, magnification 200×). Ki-67 staining highlights the large nuclei of neoplastic B cells.

Treatment and follow-up

A radiotherapy treatment on the left arm was administered. Subsequent total body PET-TC follow-ups (8 months later) showed no local residual disease, no more significant metabolic activity in axillary lymph nodes and no other evidence of generalised lymphoma. At last follow-up (10 months later) the patient was pain free and reported only a light tingling in medial side of her left forearm, with a Michigan Hand Outcomes Questionnaire (MHQ) total score of 90.5.⁹

Discussion

PLPN is a very rare tumour, always described in mixed nerves, that is, motor and sensory nerves.^1–8 Ten of the 17 PLPNs described the involvement of the sciatic nerve.⁸ Upper limb PLPNs were described only in six patients: three radial nerve,^3–5 one median nerve⁶ and two ulnar nerve involvements.^{7 8} In all the reported cases, MRI and CT scans were non-specific, showing nerve widening or a mass surrounding the nerve and diffuse swelling. Patients underwent complete or partial excision of the tumour or just biopsies2 3 10–14 followed by different protocols of chemotherapy, associated or not with radiotherapy, or radiotherapy alone.^{6 11 15} Among these 17 patients, six died in the follow-up, with a mean of 23 months (range, 6–50 months). The effective prognosis of PLPNs is hard to establish, because of the small number of cases presented in literature, also the pathogenesis is still unclear.^{3–8 16} Haematogenous spreading can be a hypothetical pattern but the common characteristic of the reported PLPNs was the lack of any other sites of lymphoma, at the time of primary tumour diagnosis. There is not yet any explanation about the predilection of some of these tumours for peripheral nerve, one possible hypothesis is protection from immunological surveillance by the blood-nerve barrier, creating a protected site for malignant lymphocytes.³ The existence of ablood-nerve barrier was established by Doinikow in 1913 and was corroborated by Waksman and Olson in later experiments.¹⁷ This barrier can also explain the low response to chemotherapy of these tumours. Our case describes the first primary lymphoma in a pure peripheral, sensory nerve. The patient developed sensory symptoms and swelling in the area of the affected nerve and ultrasound and MRI were performed prior to surgery, which did not allow a final conclusion but supported the diagnosis of a peripheral nerve sheath tumour. Lymphomatous tissue should have restricted diffusion in MRI, similarly to central nervous system lymphomas. Hence, the use of diffusion weighted imaging (DWI) could be useful for identifying peripheral lymphomas.¹⁸ However, DWI was not performed in our case. Histopathological evaluation after surgical excision revealed a lymphoma of the peripheral nerve and other examinations revealed no other tumour localisations. A PLPN is characterised by the absence of other clinical and imaging signs of central nervous system involvement and should be distinguished from primary neurolymphomatosis, a rare complication of the non-Hodgkin's lymphoma when the first event of the tumour is nervous tissue infiltration.^{14 16} Surgery consisting a complete excision should be prudently performed because tumours appear to be situated in peripheral nerves attached to the surrounding tissue^3–8 (figure 3). In our case, the involvement of a pure sensory nerve raised the question whether to proceed with a complete excision of the mass alone or oncology resection of the nerve involving healthy margins both proximally and distally and to establish surgical resection criteria. Surgical treatment is commonly followed by different protocols of chemo and/or radiotherapy, even if prognosis is still unclear; in our case report only radiotherapy was administered, with a satisfactory result. In any case, against these aggressive tumours, early diagnosis is essential to improve prognosis. In case of compression neuropathies and lesion surrounding a nerve, every physician and especially hand surgeons have to suspect and be ready to treat a PLPN because clinical signs and radiological imaging of PLPNs are superimposed.^{10 19 20} Based on our rare case, guidelines and multidisciplinary approaches to treat PLPN can be established to overcome uncertainties in medical and surgical treatment.

Patient’s perspective.

At the beginning when I went to Hand Surgery Unit for a specialist examination, I only had a bit of numbness and swelling on my left forearm; but I could never thought what I was going to face. After the first meetings with the doctor, I had to undergo a series of medical checks, with many waits and fears; all that twisting made me feel a bit lost, as it seemed that we wandered in the dark, because we did not understand what it was. An unknown mass was in my forearm, crushing my nerve. The doctor, explained me that surgical exploration and radical excision was necessary. He made me aware of all the risks of nerve damage and outcomes, so I decided to see it through. Finally, after surgery and the histological examination, I got my diagnosis, a follicular lymphoma, a malignant tumor. At that moment I felt the world collapse on me, I firstly believed that I would have lost my arm or that the tumor could spread throughout my body and into my brain. I started looking online for information about primary lymphomas of peripheral nerves, but there were only a few rare cases described, with many uncertainties about the prognosis. After the Pet-Tc scan, they told me that I had to undergo radiotherapy because of the axillary nodes involvement and the expectations were not so excellent. I have to admit that the doctors have been very close to me, always bringing me a bit of optimism; even if without my family, I would not have been able to through difficult times. When at the last Pet-Tc follow-up, we learned that there was no more that bad signal on my axillary lymph nodes, a tear felt down from my eyes. That’s crazy how our life can change at any moment. To date my way of dealing with the small problems of everyday life has totally changed, because we often don't realize what are, really, the priorities of life.

Learning points.

• Primary lymphoma of the peripheral nerve is a very rare tumour, that could affect mixed motor and sensory nerves.

• A patient suffering from peripheral nervous system symptoms needs to be always thoroughly investigated, because clinical signs of primary lymphoma of the peripheral nerves may overlap those of compression neuropathies.

• MRI and CT scans are non-specific, so surgical exploration and excision is necessary for a conclusive diagnosis.

Ethics statements

Patient consent for publication

Consent obtained directly from the patient(s).