Extramedullary plasmacytoma of thyroid - a mimicker of medullary carcinoma at fine needle aspiration cytology: A case report.

A rare case of extra medullary plasmacytoma (EMP) of thyroid gland in a 60 year old male, occurring against a background of Hashimoto's thyroiditis is reported. The fine needle aspiration cytology (FNAC) initially done as an outpatient procedure, showed atypical epithelial cells on a background of amyloid. Considering these findings we gave a diagnosis of medullary carcinoma. Histology of the total thyroidectomy specimen showed an extensive infiltration of neoplastic plasma cells against a background of Hashimoto's thyroiditis, with a bizarre Hurthle cell change. Immunohistochemistry on the histology sections confirmed the diagnosis of solitary plasmacytoma of thyroid against a background of Hashimoto's thyroiditis.

Introduction

Solitary plasmacytoma of the thyroid is an uncommon neoplasm constituting 1.4% of the extramedullary plasmacytomas (EMPs). The patients are often middle-aged to older adults, with a slight male predominance.[12] There are many reported cases of solitary plasmacytomas of the extrathyroidal sites diagnosed on fine needle aspiration cytology (FNAC) in literature.[34] A diagnosis of solitary plasmacytoma of the thyroid made during FNAC, however, to the best of our knowledge, is rare and unique.[4] The present case illustrates the difficulty in arriving at an FNAC diagnosis of solitary plasmacytoma of the thyroid, due to the presence of atypical Hurthle cells and the associated amyloid in the tumor.

Case Report

A 60-year-old male presented with a neck mass, hoarseness of voice, and dysphagia of a three-month duration. On clinical examination the thyroid gland was diffusely enlarged, more prominent on the right side, firm, and painless. The thyroid profile showed hypothyroidism. An ultrasound examination showed hypoechoic areas in both lobes suggestive of a space-occupying lesion.

The FNAC revealed a cellular aspirate composed of cells arranged in numerous acini, loose clusters, pseudopapillae, as well as singly dispersed [Figure 1a]. The cells were round to ovoid, with enlarged nuclei and fine chromatin. Many cells showed nuclear grooves as well as marked anisonucleosis, with occasional intranuclear cytoplasmic inclusions [Figure 1c]. The cytoplasm was abundant, pink, and granular in most of the cells [Figure 1b]. The background showed a few lymphocytes and spindle-shaped cells. Occasional multinucleate giant cells were observed. A pink amorphous acellular material was identified as large blobs and stained positive for Congo red [Figure 1d]. It showed an apple green birefringence on polarising microscopy.

Figure 1a

Cellular aspirate with acinar cells, papillaroid clusters, and nuclei with grooves (H and E, ×200)

Figure 1c

Cluster of cells with an intranuclear inclusion (H and E, ×400)

Figure 1b

Acini composed of pleomorphic cells with hyperchromatic nuclei and abundant pink cytoplasm (H and E, ×400)

Figure 1d

Positive staining amorphous material in smear background (Congo red stain, ×200)

A possibility of an epithelial neoplasm, either medullary carcinoma (pleomorphic variant) or a follicular variant of papillary carcinoma was given. This was due to the presence of pleomorphic epithelial cells arranged in groups, acini, and papillaroid structures. However, due to the associated amyloid, a strong possibility of medullary carcinoma over papillary carcinoma was considered. Based on this diagnosis, the patient underwent total thyroidectomy. Gross examination of the thyroidectomy specimen showed the right lobe to be with an isthmus measuring 7 × 5 × 4 cm and the left lobe measuring 5 × 4 × 3 cm. The cut surfaces of both were nodular and fleshy in appearance [Figure 2a].

Figure 2a

Cut surface of the total thyroidectomy specimen showing a lobulated fleshy appearance

Histopathology: The multiple sections studied, revealed diffuse atypical plasma cells in sheets effacing the normal thyroid parenchyma [Figure 2b]. The intervening areas and thyroid tissue at the periphery showed Hashimoto thyroiditis, with extensive oncocytic change and bizarre nuclear changes. Numerous lymphoepithelial lesions were also noted, with follicular colonization of acini by lymphocytes. Amorphous material, consistent with an amyloid, was identified amidst the neoplastic cells. A diagnosis of plasmacytoma of the thyroid gland was made on histology. A close differential considered on histology was marginal zone lymphoma with extensive plasma cell differentiation. Immunohistochemistry revealed plasmacytoid cells with diffuse positivity for CD138 [Figure 2c], and also cytoplasmic positivity for the Kappa light chain. The tumor cells were negative for CD19 [Figure 2d] and CD20. On the basis of immunohistochemistry a final diagnosis of extramedullary solitary plasmacytoma (ESP) of the thyroid was made, after the workup was found to be negative for multiple myeloma.

Figure 2b

Thyroid follicles lined by Hurthle cells with intervening sheets of neoplastic plasma cells (H and E, ×400)

Figure 2c

Neoplastic cells showing diffuse cytoplasmic positivity for CD138 indicating plasma cell diff erentiati on (IHC, ×400)

Figure 2d

Germinal center cells (reactive and part of Hashimoto thyroiditis) showing CD19 positivity (IHC, ×200)

Discussion

Extramedullary plasmacytoma is a rare lesion.[1] A diagnosis of this neoplasm by FNAC has been made at extrathyroidal sites even without the help of immunohistochemistry.[34] The present case is an example of solitary plasmacytoma of the thyroid, which was diagnosed, after FNAC, as a medullary carcinoma, for various reasons outlined below. The needle had sampled predominantly follicular epithelial cells from the periphery of the lesion, which represented changes of Hashimoto thyroiditis (the background in the aspirate showed mononuclear cells, which are predominantly lymphocytes). The predominant component of the aspirate constituted Hurthle cell clusters with bizarre nuclear morphology (mistaken for carcinoma). Some granularity of the cytoplasm and abundant acellular material, which was positive for an amyloid stain, suggested a diagnosis of medullary carcinoma on the aspirate. The neoplastic plasma cells did not constitute the component of the aspirate.

Fine Needle Aspiration Cytology, as outlined in this case, emphasises the limitation of being a diagnostic tool in all thyroid malignancies. A similar case of solitary plasmacytoma of the thyroid has been documented in literature by Bourtsos et al.,[56] who have also demonstrated this pitfall in aspiration cytology diagnosis. Hurthle cells are notorious mimics of malignant cells. They are known to show atypical nuclear changes and hyperchromasia and this has been well-documented in literature.[78] Nuclear grooves are also a feature of Hurthle cells.[8] Most probably, multiple aspirations could have avoided this misinterpretation, but even so, the presence of amyloid in the aspirate associated with some epithelial cells tilted the diagnosis toward a medullary carcinoma.

Bourtsos et al.[5] have emphasized that EMP should be considered in the differential diagnosis of a neck mass that yields discohesive cells associated with amyloid-like material. They made a diagnosis of medullary carcinoma due to the presence of plasmacytoid tumor cells with an amyloid in the background. The present authors mistook Hurthle cells for cells of a pelomorphic variant of medullary carcinoma. The confusion toward malignancy was compounded due the presence of intranuclear inclusions in these cells as well as grooves. Similarly Ridal et al.[9] diagnosed a case of EMP as lymphoplasmacytic lymphoma on cytology. Sarin et al.[10] reported five cases of EMPs on cytology and observed plasmacytoid cells with varying pleomorphisms, bi- and multinucleation, and mitotic figures. All these features posed a diagnostic challenge for them on cytological evaluation.

At histology, although plasmacytoma was considered as a diagnosis, the other close differential was marginal zone lymphoma, with extensive plasma cell differentiation, which was the more common occurrence in the thyroid, as compared to plasmacytomas.[611] On immunohistochemistry, the plasmacytomas were negative for CD45, CD19, and CD 20, and strongly positive for CD138.[12] Marginal zone lymphomas were, on the contrary, positive for CD45, CD19, and CD20, and would show positivity for CD138, depending on the plasma cell differentiation. The present case was strongly positive for CD138, with light chain restriction for kappa chains, which favored a diagnosis of plasmacytoma.

In conclusion, EMP of the thyroid can be diagnosed on cytology with multiple aspirations, to avoid sampling error and to arrive at the right diagnosis. Amyloid-like material can be associated with this type of tumor and not necessarily be a component of medullary carcinoma alone. The other differentials like lymphoproliferative lesions and plasmacytomas must be kept in mind in the setting of autoimmune thyroiditis, which can be diagnosed on cytology.