Intrathyroidal Plasmacytoma with Pleomorphic Multilobated Bizarre Cells: A Rare Primary Clinicopathological Presentation Mimicking Anaplastic Carcinoma of Thyroid

Abstract

Background

Plasmacytoma involving thyroid gland is infrequent and can present as either primary extramedullary plasmacytoma or secondary to multiple myeloma.

Methods and Results

We present a case of 71 years old male who complained of a huge anterior neck swelling accompanied by dysphagia and dyspnoea. Fine needle aspiration cytology was suggestive of anaplastic carcinoma of thyroid (ATC), however, the subsequent histomorphology supported by immunohistochemistry (IHC) astoundingly favoured the diagnosis of plasmacytoma. Further evaluation revealed the presence of lymphadenopathy and single bone lesion in the present case which was rather suggestive of secondary involvement of thyroid to multiple myeloma. However, the case was unique in view of its presentation as a rapidly enlarging thyroid mass associated with stridor and cytomorphological findings which were of an undifferentiated malignancy favouring ATC. The use of a broad and judicious IHC panel clinched the final diagnosis of plasmacytoma.

Conclusion

The present case emphasizes the diligent use of IHC in such cases given different therapeutic and prognostic implications.

Introduction

Plasmacytoma involving thyroid gland is rare which can manifest as primary extramedullary plasmacytoma (EMP) or as secondary involvement by multiple myeloma (MM) [1–6]. Association of intrathyroidal plasmacytoma with Hashimoto’s thyroiditis has been found in only 10 cases reported so far [1–5]. The diagnosis is usually suspected on histomorphology as neoplastic plasma cells resemble their normal counterpart and confirmed with immunohistochemistry (IHC) for lineage and clonality [7]. Plasmacytoma with multilobated or bizarre nuclei along with high grade morphology is an unusual morphological variant and can lead to erroneous diagnosis of non-hematological malignancy [8, 9]. We describe a rare case of intrathyroidal plasmacytoma with pleomorphic multilobated bizarre neoplastic cells masquerading as Anaplastic Carcinoma of Thyroid (ATC) on clinical and pathological features.

Case Report

A 71-year-old male, chronic smoker with no significant past or family history presented with anterior neck swelling of 4–5 months duration associated with difficulty in swallowing and breathing discomfort on and off. The patient was initially evaluated elsewhere. The complete hemogram, liver function tests and kidney function tests were within normal limits. Serum calcium level was 10 mg/dL (normal range: 8.6–10.3 mg/dL). Thyroid function tests revealed hypothyroidism [serum free T3: 4.91 pmol/L (normal range: 2.3–4.1 pmol/L); free T4: 7.20 pmol/L (normal range: 12–30 pmol/L) and TSH: 65.7 µIU/L (normal range:0.5–5.0 µIU/L)]. Ultrasound neck showed hypoechoic mass in both the lobes of thyroid and significant bilateral cervical lymphadenopathy. Fine needle aspiration cytology (FNAC) from anterior neck swelling revealed pleomorphic neoplastic cells with few bizzare forms and was highly suggestive of ATC (The Bethesda System of Reporting Thyroid Cytology Category VI—Malignant).

Further, positron emission tomography-computed tomography (PET-CT) was performed which revealed bilateral thyroid lobe enlargement with retrosternal extension. The thyroid gland was seen encasing the oesophagus and trachea causing luminal narrowing. Multiple FDG avid (SUV max: 12.9), ill-defined heterogeneously enhancing hypodense discrete and coalescent nodular lesions were noted involving both lobes of thyroid (largest measuring 4 × 3.5 × 2 cm) and infiltrating the prevertebral fascia. Multiple FDG avid discrete and coalescent bilateral cervical and mediastinal lymphnodes (largest measuring 8.1 × 7.2 × 4.0 cm) were seen. Single FDG avid intra-osseous skeletal lesion was seen in the shaft of left femur likely metastatic (Figs. 1(a–c)).

Fig. 1.

a-c Fused axial PET and CT images shows diffuse uptake in thyroid gland which are symmetrically enlarged. Few nodular enhancing deposits are seen in the vicinity of the lesion compressing the bilateral neck vessels. Tracheal air column shows no significant luminal compromise

The patient was subsequently referred to our institute (tertiary cancer care centre). The poor prognosis associated with the disease was explained to the patient. A trucut biopsy from thyroid mass was advised to re-affirm the previous diagnosis and to decide for further definite management. For immediate symptomatic relief, patient underwent palliative radiation therapy (RT) (20Gray/5 fractions) and showed improvement. The hematoxylin and eosin (H & E) stained slides (Figs. 2(a–d)) revealed diffuse proliferation of pleomorphic neoplastic cells, polygonal to round in shape, with multilobated and bizarre nuclei. Significant mitoses including atypical forms were noted. Occasional residual thyroid follicles were also evident. Histomorphological features were suggestive of undifferentiated malignancy favouring ATC.

Fig. 2.

H & E stained linear cores from thyroid swelling (a) shows proliferation of neoplastic cells in diffuse sheets (b) shows few entrapped thyroid follicles (arrow) in tumor tissue (c) shows pleomorphic bizarre neoplastic cells (d) shows significant mitosis (arrow) and multilobated neoplastic cells

On primary immunohistochemistry (IHC) panel, the tumor cells were positive for leukocyte common antigen (LCA) while negative for cytokeratin (CK), epithelial membrane antigen (EMA), paired box gene 8 (PAX8) and thyroid transcription factor (TTF1). Subsequently, tumor cells were negative for CD20, CD3, and PAX5 while positive for CD79a. On further IHC, tumor cells were positive for CD138 (patchy), Multiple myeloma-1 (MUM-1) with kappa light chain restriction by in situ hybridization (ISH) (Figs. 3(a–d)). CD138 was patchy in view of anaplastic morphology. Ebstein barr virus encoded RNA-in situ hybridization (EBER-ISH) was negative. MIB-1 index was 3–5%. These findings provided a tangible evidence for final diagnosis of intrathyroidal plasmacytoma. Subsequently, serum protein electrophoresis also showed distinct M-band in the gamma region with M band concentration of 0.67 g/dl (Fig. 4) and reaffirmed the diagnosis.

Fig. 3.

Immunohistochemistry (a) CK was negative in tumor cells while entrapped thyroid follicles were positive (arrow) (b) CD138 was patchy positive in tumor cells (c) and (d) shows kappa lambda by ISH highlighting kappa restriction, respectively

Fig. 4.

Serum protein electrophoresis showed distinct M-band in Gamma region. The M-band concentration is 0.67 g/dl

The case was discussed in multidisciplinary tumor board meeting and patient underwent palliative radiation therapy (RT) (20Gray/5 fractions) and got symptomatic relief for difficult breathing. However, patient was lost to follow up.

Discussion

Plasmacytoma is defined as a solitary neoplasm of plasma cells with clonal expansion without evidence of plasma cell (multiple) myeloma or end organ damage due to plasma cell neoplasm. Plasmacytomas are classified as solitary plasmacytoma of bone and extramedullary plasmacytoma, the latter is defined as involvement of soft tissue by neoplastic plasma cells without bone marrow involvement [1, 3, 7]. Thyroid involvement by EMP is rare or it may also be infiltrated due to systemic involvement by MM [10, 11].

In a study by Kovacs et al. [12], majority of cases of solitary plasmacytoma of the bone progressed to MM while EMP remained localized with 83% showing no evidence of disease after a mean follow-up of 56 months duration.

The present case although revealed lymphadenopathy and single bone lesion (in femur), hence did not fulfil the criteria for EMP and was rather suggestive of secondary involvement of thyroid by multiple myeloma. However, the primary presentation was of a large rapidly enlarging thyroid mass associated with dysphagia and stridor. Moreover, cytological and histomorphological findings were of an undifferentiated malignancy which was evocative of ATC in the presented clinical context.

The broad IHC panel (CK, LCA, and Human melanoma black (HMB45)) which is advocated for undifferentiated malignancy helped to navigate to the final diagnosis in the present case. Although, thyroid involvement by hematological malignancy (commonly, Diffuse Large B cell Lymphoma (DLBCL)) is well known, but the neoplastic cells of DLBCL are usually monomorphic in majority of the cases. Moreover, negative CK immunoexpression has been well reported in ATC [13]. The tumor cells were negative for CD20, PAX5 (B cell markers), CD3 (T cell marker) and CD30, largely ruled out DLBCL, T-cell lymphoma and Anaplastic Large Cell Lymphoma. Subsequently, CD79a, CD138 was positive with kappa light chain restriction by ISH while EBER-ISH was negative, hence, provided the evidence to render the final diagnosis of intrathyroidal plasmacytoma.

The diagnosis of plasmacytoma with conventional morphology is not much challenging as they show sheets of neoplastic plasma cells which resemble the normal plasma cells with variable number of plasmablastic cells in between. On cytology (FNAC) examination, they can mimic medullary thyroid carcinoma and therefore, serum calcitonin & CEA levels can help to distinguish them. On IHC, they show positive expression of CD138, CD38 with variable CD79a and LCA expression while CD20 is negative. Clonality studies show kappa/lambda light chain restriction. Plasmacytomas are almost always negative for Ebstein Barr Virus (EBV).

Plasmacytoma with multilobated and bizarre cells is an unusual and diagnostically challenging histomorphological variant associated with high grade morphology and aggressive clinical course [8, 9]. Moreover, this can mislead to an erroneous diagnosis of non-haematological malignancy, especially epithelial malignancy when manifesting in thyroid gland. Hence, the accurate diagnosis is of importance as these patients are subjected to further prognostic and predictive cytogenetic tests (CKS1β amplification, CDKN2C deletion, TP53 deletion and IGH rearrangements). A targeted probe for individual IGH rearrangements (CCND1/IGH, FGFR3/IGH, MAF/IGH, MAFB/IGH) should be carried out if IGH rearrangement is present for risk assessment. These patients are subsequently subjected to RT & chemotherapy or may be subjected to autologous stem cell transplantation.

To conclude, a primary presentation of symptomatic thyroid mass revealing plasmacytoma with multilobated bizarre cells is a rare presentation and can be misdiagnosed as non-haematological malignancy, especially ATC. A diligent histomorphological examination and algorithm based judicious IHC assessment can help for accurate diagnosis due to distinct therapeutic and prognostic implications.

Author Contributions

Substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data–SP, DB, MK, MA, AJ. Drafting the article and revising it critically for important intellectual content–SP, HD, GG, AS, GD, VPBK. Final approval of the version to be published–SP, DB, HD.

Funding

The authors did not receive support from any organization for the submitted work nor was there any funding to conduct the study or to assist with manuscript preparation.

Data Availability

Availability of data and material is possible upon reasonable request, deidentified for maintenance of anonymity and compliance with IRB approval.

Code Availability

Not applicable. All authors confirm they have meaningfully contributed to the research and read and approved the final manuscript.

Declarations

Conflicts of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethical Approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board (Rajiv Gandhi Cancer Institute & Research Centre),vide the ethical approval letter number RGCIRC/IRB-BHR/44/2022.

Consent to Participate and Publication

Written informed consent was obtained from the patient for publication of this case report and accompanying images.