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Ann Indian Acad Neurol
Ann Indian Acad Neurol
AIAN
Ann Indian Acad Neurol
Annals of Indian Academy of Neurology
0972-2327
1998-3549
Wolters Kluwer - Medknow India

AIAN-27-447
10.4103/aian.aian_28_24
Letters to the Editor
Polyneuropathy Unveiling a Hidden Hepatic Plasmacytoma: An Extremely Rare Association
Makharia Archita
Agarwal Ayush
Garg Divyani
Shamim Shamim A. 1
Yadav Rajni 2
Mani Priyanka 2
Radhakrishnan Divya M.
Pandit Awadh K.
Srivastava Achal K.
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
1 Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Address for correspondence: Dr. Ayush Agarwal, Department of Neurology, AIIMS, New Delhi, India. E-mail: ayushthetaurian@gmail.com
Jul-Aug 2024
19 4 2024
27 4 447449
11 1 2024
03 3 2024
12 3 2024
Copyright: © 2024 Annals of Indian Academy of Neurology
2024
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pmcDear Editor,

Multiple myeloma (MM) is the most common primary bone malignancy in adults.[1] In contrast, solitary plasmacytomas are a rare form of plasma cell dyscrasia which can present in medullary (bone) or extramedullary locations, of which hepatic plasmacytomas are exceedingly rare.[123] While polyneuropathy is well established in myeloma spectrum disorders, its occurrence alongside extramedullary solitary plasmacytomas is unusual. We report a case of polyneuropathy associated with a solitary hepatic plasmacytoma.

A 45-year-old male patient presented with a 5-year history of gradually progressive sensorimotor quadriparesis. He first developed paresthesia and numbness over both feet, which progressed to mid-thigh followed by fingers to distal forearm over 2 years. Thereafter, he had slippage of footwear without awareness and difficulty in rising from sitting position for the past 3 years. He was unable to button his shirt and required assisted ambulation in the past year. He also experienced involuntary weight loss of 25–30 kg over the past 3 years and observed hyperpigmentation, thickening, and excessive hair growth over his limbs and face. He had no history of orogenital ulcers, rash, photosensitivity, or polyarthralgia.

Clinical examination revealed generalized wasting, grade 1 clubbing, bilateral pitting pedal edema up to mid-shin, and multiple lymph nodes in the upper and middle cervical groups bilaterally, which were firm, nonmobile, nontender, and nonmatted. He had hyperpigmentation, skin thickening, and hypertrichosis, interspersed with hypopigmented patches over the limbs, predominantly over the extensor surface and his face. He had no organomegaly, pleural effusion, or ascites. Fundus examination was normal. His limbs were hypotonic with a power of (Medical Research Council [MRC] scale) 5/5, 4/5, and 4-/5 at the shoulder, elbow, and wrist joints, respectively, and 4+/5, 4-/5, and 1/5 at the hip, knee, and ankle, respectively. Hand grip strength was 5%–10% bilaterally. His plantar reflex was mute with generalized areflexia. He had pan-sensory loss, with hyperalgesia and allodynia below the knees and mid-forearm, and had thickened common peroneal and ulnar nerves.

Investigations revealed polycythemia (hemoglobin- 18 g/dl and hematocrit- 57.3%) and hyperuricemia. Liver and renal functions, human immunodeficiency virus, hepatitis B and C, Venereal Disease Research Laboratory, serum and urine protein electrophoresis, antinuclear antibody, extractable nuclear antigen, antineutrophilic cytoplasmic antibody, and vascular endothelial growth factor were normal. Serum free light chain assay showed increased lambda and kappa chains, with kappa/lambda ratio of 1.72 (0.26–1.68). His serum uric acid levels were normal (6.8 mg/dl; normal <7 mg/dl). JAK2 mutation was negative, and serum immunoglobulin (Ig) levels showed elevated IgG. Nerve conduction studies showed nonrecordable responses in all motor and sensory nerves tested. Cerebrospinal fluid analysis revealed an albuminocytologic dissociation, with no cells, protein level of 134 mg/dl (normal 15–45 mg/dl), and glucose level of 60.7 mg/dl (corresponding blood glucose- 112 mg/dl).

An immune-mediated neuropathy was considered, and further testing with abdominal fat biopsy, serum interleukin-6, tumor markers, paraneoplastic panel, and toxicology screen yielded negative results. Whole body fluorodeoxyglucose (FDG)-positron emission tomography revealed a metabolically active gall bladder mass infiltrating into the liver with multiple FDG-avid locoregional lymph nodes [Figure 1]. Contrast-enhanced magnetic resonance imaging of the abdomen revealed a lesion in segment VIII of the liver, showing diffusion restriction with patchy areas of non-rim arterial phase enhancement indicative of a highly malignant etiology. An ultrasound-guided biopsy of this liver mass revealed a solitary plasmacytoma [Figure 2]. Subsequent bone marrow biopsy demonstrated 7% plasma cells.

Figure 1 (a) FDG MIP image shows focal area of increased metabolism in the liver and abdominal lymph nodes. (b, c) Fused axial and coronal PET/CT images show an FDG-avid mass arising from the gall bladder and infiltrating into adjacent segments V/VIII of the liver (green arrow). (d, e) Fused axial PET/CT image shows FDG-avid, enlarged periportal, precaval, and paracaval lymph nodes (gray arrow). CT = computed tomography, FDG = fluorodeoxyglucose, MIP = maximum intensity projection, PET = positron emission tomography

Figure 2 (a) Sections examined from liver biopsy show cores of liver tissue with sheets of atypical cells, 100× (H and E). (b) The atypical cells are round and contain moderate amount of eosinophilic cytoplasm and eccentrically placed nuclei, 400× (H and E). (c, d) These cells are immunopositive for CD138 and MUM1, 400× (IHC). (e, f) The cells are negative for kappa, while they are positive for lambda, 200× (IHC). H and E = hematoxylin and eosin, IHC = immunohistochemistry

The patient did not meet the criteria for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) [Supplementary Table 1]. Therefore, based on the 2014 International Myeloma Working Group Criteria, he was diagnosed as extramedullary solitary hepatic plasmacytoma with minimal marrow involvement (less than 10% plasma cells in the bone marrow).[3] He was administered chemotherapy with bortezomib, cyclophosphamide, and dexamethasone. At 3 months follow-up, the power at the ankle, knee, and wrist improved to MRC grade 3/5, 4/5, and 5/5, respectively.

Supplementary Table 1 Diagnostic criteria for POEMS syndrome (5)

Mandatory criteria	Polyneuropathy	
	Monoclonal plasma cell proliferative disorder	
Major criteria	Sclerotic bone lesions	
	Castleman's disease	
	Elevated VEGF	
Minor criteria	Organomegaly (Hepatomegaly, splenomegaly, or lymphadenopathy)	
	Extravascular volume overload (edema, pleural effusion, or ascites)	
	Endocrinopathy (adrenal, thyroid, pituitary gonadal, parathyroid, pancreatic)	
	Skin changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis, flushing, white nails)	
	Papilledema	
	Thrombocytosis/Polycythemia	
The presence of both mandatory criteria at least one major criteria and at least one minor criteria are needed for the diagnosis of POEMS syndrome

The incidence of extramedullary plasmacytomas is 7%–18% at MM diagnosis, increasing to 20% during relapse.[4] Nearly 85% of extramedullary plasmacytomas localize to the head and neck mucosa, primarily within the upper respiratory tract.[5] Although cases affecting the gastrointestinal tract, bladder, lung, and testis have also been reported, the literature on hepatic plasmacytoma is sparse.[123]

Approximately 10% of patients with a chronic sensorimotor neuropathy of unknown origin have an associated monoclonal gammopathy. Neuropathies associated with plasma cell dyscrasias are seen with monoclonal gammopathy of undetermined significance (particularly of the IgM subtype), MM, Waldenström’s macroglobulinemia, amyloidosis, Castleman’s disease, POEMS syndrome, and cryoglobulinemia. There are three major subtypes of peripheral neuropathy in this context: distal demyelinating symmetric neuropathy, chronic inflammatory demyelinating polyneuropathy–like, and axonal sensorimotor. Probable mechanisms include a paraneoplastic phenomenon, an immune-mediated mechanism, and direct infiltration of nerves by the plasma cells.[67]

Despite the well-established link between polyneuropathy and plasma cell dyscrasias, their association with solitary plasmacytoma is sparsely documented. Moreover, the presentation of neuropathy as the primary indicator for an extramedullary plasmacytoma is exceptionally rare, as observed in our patient. Existing records linking neuropathy to plasmacytomas predominantly revolve around those associated with bone-related plasmacytomas.[78] Even fewer instances document neuropathy in connection with extramedullary plasmacytomas (thymus has been associated).[910] Interestingly, no documented case exists associating hepatic solitary plasmacytoma with neuropathy until now.

Due to the typical localized and singular nature of these lesions, the peak monoclonal protein observed in affected patients is often small and challenging to detect during serum protein electrophoresis. Majority of patients with solitary plasmacytoma have lambda light chain in contrast to MM, where kappa light chains predominate by 2:1 ratio.[10] This was evident in our patient where no M band was detected, and liver mass biopsy revealed lambda expression.

Moreover, the presence of plasma cells in the liver or spleen indicates a more aggressive form of MM, significantly impacting treatment strategies.[3] This often necessitates intense chemotherapy or consolidation therapy with autologous hematopoietic stem cell transplantation, as implemented in our patient’s treatment plan.

The association between polyneuropathy and extramedullary solitary plasmacytoma remains a rare and intriguing relationship. Not all instances of plasmacytomas linked with polyneuropathy are categorized as POEMS syndrome. Clinicians should consider solitary plasmacytoma as a potential etiology for cryptogenic peripheral neuropathy as the diagnosis and treatment could lead to favorable clinical outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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