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Multiple myeloma is the most common primary malignancy of the bone. Although it has a host of systemic manifestations, it rarely presents as a mass involving the thyroid cartilage. Through this study, we aim to describe one such patient: A 60-year-old man- who came to us with the chief complaint of rapidly expanding neck swelling and dysphagia. During the course of workup, patient sustained a fracture of the humeral shaft. It was subsequently revealed that he had a mass lesion originating from the thyroid cartilage. Needle aspiration cytology from the latter depicted myeloma cells as well as plasma blasts. He also had multiple osteolytic lesions in his skull and mandible. Serum protein electrophoresis showed characteristic M band in the globulin region. Based on the above findings, a diagnosis of multiple myeloma was made and patient advised chemotherapy which he refused. At the last follow up, he was alive and showed no further deterioration of the existing lesions.
Even though rare, multiple myeloma must be kept as one of the differentials in all elderly males presenting with a neck mass. Timely and appropriate treatment with radiation/ chemotherapy can lead to disease remission.
Keywords: Multiple myeloma, Thyroid cartilage, Neck swelling, Osteolytic lesions
Plasma cell neoplasms [MOU1] (PCN) result from excessive proliferation of abnormal plasma cells in the bone marrow. Multiple Myeloma (MM), solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are all subtypes of PCN .
MM is the most common primary bony malignancy, usually seen in elderly males above 50 years of age . The hallmark feature of MM is the presence of myeloma or ‘M’ protein in the serum along with excessive secretion of Immunoglobulins (Igs), which are responsible for the systemic manifestations of the disease. On the other hand, SPB is a lesion in a single bone without the systemic complications seen in MM i.e. hypercalcemia, renal insufficiency, anaemia and amyloidosis . When a similar pathology occurs outside the bone, it is called an EMP .
Classically, MM appears as diffused, osteolytic lesions involving the skeletal system . However, atypical presentations of MM involving the thyroid cartilage have also been reported [5-22].
We hereby present the case of a 60-year-old male who presented to us with a rapidly progressing neck swelling, which turned out to be MM invading the thyroid cartilage.
A 60-year-old male presented to the surgical out-patient clinic with chief complaints of left-sided neck swelling for the past seven days, which was insidious in onset but rapidly progressive, causing him to have dysphagia for the past 3 days (more for solids than liquids). He also gave a history of non-specific bony pains associated with low backache for the past one year. Constitutional symptoms like anorexia and weight-loss were present. Severe pallor was noted. Clinical examination of the neck showed a non-tender, 3 x 2 cm ovoid swelling which was firm in consistency, had a smooth surface with well-defined margins and was located approximately 1 cm lateral to midline and 3cms above suprasternal notch (Figure 1A). It was mobile with deglutition. Auscultation of the swelling did not reveal any audible bruit. The patient was admitted for further evaluation and management. His hematological parameters revealed severe anemia (Hb-3.6) with thrombocytopenia (Platelet count-80,000) and reduced total white blood cell (WBC) count (pancytopenia). Peripheral smear showed presence of normocytic normochromic along with microcytic hypochromic cells. He was transfused 3 units of packed red blood cells and adequately resuscitated. During the course of admission, the patient had a fall from bed following which he developed swelling and tenderness over the left arm, without any distal neurological or vascular impairment. X rays showed a fracture of the left proximal shaft of humerus (Figure 1b), which was graded according to the Mirel’s criteria as we suspected it to be pathological. The score obtained was 6 and hence, fracture was managed conservatively with a U-slab. Our two chief differentials at this point were metastatic carcinoma of the thyroid and multiple myeloma. To differentiate between the two and arrive at a definitive diagnosis, a number of tests were performed.
With the exception of serum uric acid (10.9 mg/dl), serum thyroid stimulating hormone (TSH) (10.75 microIU/ml) and erythrocyte sedimentation rate (ESR) (120 mm/h by Westergen method), remaining blood investigations were all within normal limits, including serum calcium, creatinine and alkaline phosphatase (ALP). Ultrasonography (USG) of the suspicious nodule showed a mass abutting the left thyroid cartilage and guided needle aspiration cytology showed cellular smears with dispersed cell population comprising of plasma blasts, plasma cells and interspersed chondrocytes and normal thyroid follicular epithelial cells in proteinaceous background with a possibility of myeloma. Skeletal survey -X-ray and Computerized Tomography (CT) of the patient revealed diffuse osteolytic lesions in the mandible, skull and the clavicle (Figure 2B). The CECT scan of head and neck region showed a homogenously enhancing mass lesion in the visceral space along the left thyroid cartilage lamina, causing destruction and extending into the larynx (Figure 2A).
Serum protein immune-electrophoresis was carried out which was suggestive of Monoclonal gammopathy (“M” spike seen in gamma globulin region) (Figure 3). Free lambda (light) chain level was also elevated, being 336mg/L (reference range 8.3-27 mg/L), along with a raised free kappa/lambda ratio (0.09). Bone marrow biopsy was inconclusive with plasma cells accounting for 3% of the total cell population.
After co-relating patient’s clinical, radiological, laboratory as well as histopathological features, a final diagnosis of MM involving the thyroid cartilage with pathological shaft humerus. Patient was planned for a Bortezomib and Lenalidomide based chemotherapy and concomitant radiotherapy for a better 5-year survival, which he refused. At 3 months follow-up, there was no further deterioration or increase in size of the existing lesions and the fracture had united.
The mean age of presentation of MM is about 60 years which is a decade younger than that of SPB and EMP . The condition is frequently preceded by a stage of monoclonal gammopathy of undetermined significance (MGUS) .
The defining feature of MM is clonal bone marrow plasma cell count ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events :
1) Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
a) Hypercalcaemia: Serum calcium > 0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (>11 mg/dL)
b) Renal insufficiency: creatinine clearance 177 μmol/L (>2 mg/dL)
c) Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or a haemoglobin value
d) Bone lesions: one or more osteolytic lesions on skeletal radiography
• Any one or more of the following biomarkers of malignancy:
a) Clonal bone marrow plasma cell percentage ≥60%
b) Involved: uninvolved serum free light chain (of immunoglobulins) ratio ≥100:1
c) >1 focal lesion on Magnetic Resonance Imaging (MRI) studies
Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish MM from solitary plasmacytoma with minimal marrow involvement .
Extramedullary tumours form a very small percentage of PCNs and 80 to 90% occur in the head and neck region. Larynx is involved in 6 to 8% of such cases . MM involving the thyroid cartilage is exceedingly rare [7,9,22].
The presence of cartilaginous involvement in MM is explained by two theories-direct invasions by an adjacent plasmacytoma or by the osseus transformation theory which suggests that the cartilage may undergo osseus transformation with a proper marrow space and this may be the site of origin of the MM . Osseus metaplasia has been proven in cricoid and thyroid cartilages and hence could prove to be the major mechanism for MM arising at such sites but due to the extreme rarity of this condition, it is very difficult to say with certainty. Overall, MM has a very poor prognosis with 5-year survival of 18% and mean survival of 2 years .
The differential diagnosis in an elderly male presenting with a neck swelling can be varied. Since, in our case, it was a recent onset swelling which was rapidly progressive in size along with movement on deglutition, a probable diagnosis of solitary thyroid nodule most likely malignant was thought of as the first differential. Further imaging helped us identify thyroid cartilage as the tissue of origin of the swelling. Fine needle aspiration cytology (FNAC), bone marrow aspirate and a serum M band helped us make the final diagnosis. The lack of classical findings on bone marrow aspirate must be borne in mind and other findings such as bony involvement must be thoroughly evaluated. All elderly patients presenting with pathological fractures warrant further assessment with serum ALP, prostate specific antigen and carcino-embryonic antigen levels to rule out obvious metastasis.
A summary of the findings of similar studies and how they compare with ours is given in Table 1.
The differential diagnosis of a midline neck swelling can be varied and a broader perspective must be kept while investigating such cases. MM involving the head and neck cartilages is a rare diagnosis which must be kept in mind while investigating such cases, especially in the elderly age group and a high index of suspicion regarding the same can help avoid misdiagnosis and patient mismanagement.
The authors would like to thank the patient and his family for giving us the permission to publish his details.
CONFLICT OF INTERESTS AND SOURCE OF FUNDING
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