Liquid-Based Cytologic Findings of Solitary Extramedullary Plasmacytoma in Thyroid: A Case Report Identified With Fine-Needle Aspiration Cytology Chung Hun Lee, M.D.,1 Yoon Yang Jung, M.D.,2 Yul Ri Chung, M.D.,3 and Han Suk Ryu, M.D., Ph.D.3*
Preoperative cytologic diagnosis of solitary extramedullary plasmacytoma (SEP) presents a challenge to cytopathologists because this tumor rarely occurs as a primary thyroid malignant neoplasm. In this report, we provide the first description of liquid-based cytomorphologic findings of SEP observed on fineneedle aspiration biopsy (FNAB) of the thyroid. A 56-year-old woman with a history of Hashimoto thyroiditis presented with a growing nodule in the thyroid. The liquid-based preparation obtained from FNAB showed numerous dispersed plasmacytoid cells with occasional loosely cohesive aggregates of tumor cells. Cells were round to oval in shape, with eccentrically located nuclei. Hyalinized perinuclear vacuoles were found in the cytoplasm of the tumor cells. Initial cytological findings, including those of immunochemistry using a cell block preparation, were consistent with plasmacytoma. Histopathological examination subsequent to thyroidectomy revealed a plasmacytoma in the thyroid. Plasma cell neoplasms were not concurrently detected in tissues other than the thyroid. On the basis of preoperative FNAB findings, a specific diagnosis of SEP in the thyroid can be difficult because this tumor is rare. Moreover, diagnosis is impeded because SEP in the thyroid resembles other, more common thyroid lesions, including both benign and malignant neoplasms. Careful cytomorphologic examination and supportive studies may be required to fully confirm a diagnosis of SEP. Diagn. Cytopathol. 2014;42:964–969. VC 2014 Wiley Periodicals, Inc. 1 Department of Pathology, Chung-Ang University Hospital, ChungAng University College of Medicine, Seoul, South Korea 2 Department of Pathology, Samsung Medical Center, Seoul, South Korea 3 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea *Correspondence to: Han Suk Ryu, M.D., Ph.D., Department of Pathology, Seoul National University Hospital, 28 Yongon-dong, Jongro-gu Seoul 110-799, Seoul, South Korea. E-mail: [email protected] Received 5 February 2013; Revised 16 September 2013; Accepted 3 December 2013 DOI: 10.1002/dc.23086 Published online 13 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
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Key Words: extramedullary plasmacytoma; thyroid; fine-needle aspiration; liquid-based preparation
Solitary extramedullary plasmacytoma (SEP) most commonly occurs in the head and neck region, primarily in the upper respiratory tract.1 Thyroidal SEP is rare, and the cytomorphologic findings are not clearly differentiated from those of other, more common thyroid tumors, both benign and malignant. Therefore, diagnosis of thyroidal SEP on the basis of fine-needle aspiration biopsy (FNAB) findings is challenging. Recently, liquid-based cytology has gained favor as an alternative preparation method to the conventional smear for FNAB analyses.2,3 However, the cytologic features of thyroid lesions could substantially differ depending on the method of preparation (liquid-based or conventional).4,5 Although a few studies have reported the cytomorphologic findings associated with SEP, to our knowledge, no publications have discussed the liquid-based cytologic findings of SEP.6–9 Additionally, the aspiration cytology findings of thyroidal SEP have only been discussed in a few prior reports.10,11 Here, we present the first case report of thyroidal SEP diagnosed by FNA cytology performed using a liquid-based method.
Case Report A 56-year-old woman with a 2-year history of Hashimoto’s thyroiditis presented with a growing, palpable thyroid nodule. She was clinically euthyroid; thyroid function test results were within normal limits, with the exception of the serum thyroglobulin level, which was elevated at 457.7 ng/mL (reference range: 2.0–70.0 ng/mL). C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
SOLITARY EXTRAMEDULLARY PLASMACYTOMA OF THE THYROID
Fig. 1. Cytopathologic findings. A: Tumor cell clusters and individually dispersed tumor cells against a clear background (Papanicolaou stain, 2003) with cohesive aggregates of tumor cells. B: A representative feature of cohesive clusters of plasmacytoma (Papanicolaou stain, 1,0003). C: Binucleated tumor cells are apparent at the center. Abundant granular cytoplasm and eccentrically located nuclei are reminiscent of medullary carcinoma and Hurthle cell neoplasm. Tumor cells show clumped chromatin with inconspicuous small nucleoli and perinuclear halo (Papanicolaou stain, 1,0003). D: Tumor cell aggregates. Irregularity of nuclear membrane, pseudoinclusion, and spindle-shaped cells are absent (Papanicolaou stain, 1,0003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Neck ultrasonography revealed a 1.3-cm thyroid nodule that had grown since the patient’s last examination, as well as multiple, apparently stable cystic nodules. Ultrasonography-guided FNAB was performed on the growing thyroid nodule. The FNAB samples were submitted for processing and liquid-based cytology slides were prepared according to SurePathTM (Becton Dickinson Diagnostics-TriPath, Burlington, NC) protocols. The cytologic results were suggestive of plasmacytoma. Long bone radiography revealed no evidence of tumor involvement in the form of multiple myeloma. Complete
blood cell count results and peripheral blood cell morphology analysis were within normal limits. Serum calcium and potassium levels were also unremarkable. Monoclonal immunoglobulin was not detected in serum and urine samples. Histological analysis of bone marrow aspirate indicated normal architecture. Two weeks after FNAB, total thyroidectomy was performed. To date, there is no evidence of progression to multiple myeloma on the basis of bone marrow needle biopsy findings, serum test results for M proteins, and urine test results for M proteins. Diagnostic Cytopathology, Vol. 42, No 11
965
Diagnostic Cytopathology DOI 10.1002/dc
LEE ET AL.
Fig. 2. Immunocytochemical staining of a cell block preparation. Tumor cells show (A) strong membrane staining for CD138, as well as strong expression of (B) CD79a and (C) the lambda light chain. Tumor cells do not show expression of (D) CD20 (A–D, 4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Cytologic and Immunocytochemical Findings The FNAB liquid-based preparation comprised several tumor cell clusters and individually dispersed tumor cells against a clear background, with occasional colloid materials (Fig. 1A). The cells were round to ovoid in appearance with abundant granular cytoplasm and occasional perinuclear clearing. Round nuclei were eccentrically located, and no nuclear membrane irregularity was noted. Binucleated cells were occasionally present. The chromatin was coarsely clumped with small single or multiple nucleoli (Figs. 1B–D). No nuclear pseudoinclusions were 966
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found. Immunocytochemical staining was performed, using the cell block technique. Paraffin-embedded samples were sliced at a thickness of 4 lm, and each section was prepared for immunocytochemical detection. For heat-induced epitope retrieval, the sections were processed with Tris-EDTA (pH 9.0) solution for 20 min, after being de-waxed with xylene and rehydrated using a graded series of ethanol. Sections were then incubated in a peroxidase blocking solution (3% H2O2) for 10 min at room temperature, and primary antibodies were added. Subsequently, the secondary antibody was added, sections
Diagnostic Cytopathology DOI 10.1002/dc
SOLITARY EXTRAMEDULLARY PLASMACYTOMA OF THE THYROID
Fig. 3. Gross and histopathologic findings. A: Gross examination reveals a well-demarcated, reddish-brown tumor, located between two hyperplastic nodules. B: Low-power view (hematoxylin and eosin stain, 12.53) shows the encapsulated tumor nodule against a background of hyperplastic nodules with lymphocytic infiltration. C: The tumor is composed of round to polygonal plasma cells with mild to moderate pleomorphism (hematoxylin and eosin stain, 4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
were counterstained with Mayer’s hematoxylin, and the reaction was visualized using diaminobenzidine. Additional immunohistochemical staining was performed on a laryngeal plasmacytoma (as a positive control) and a papillary thyroid carcinoma (as a negative control). Immunocytochemical staining for leukocyte common antigen (2B11 (1) 1 PD7/26 (1); Ready-to-Use, Dako, CA), CD138 (Syndecan-1; 1:50, Bio SB, CA), and CD79a (SP18; 1:100, Thermo, CA) was strongly positive in plasmacytoid cells (Figs. 2A and B). However, immunocytochemical staining for pan-cytokeratin (AE1/AE3; 1:300, Thermo, CA), thyroid transcription factor-1 (SPT24; 1:100, Leica, Newcastle, UK), thyroglobulin (TGB04 (2H11) 1 TGB05 (6E1); 1:500, Thermo, CA), calcitonin (SP17; 1:100, Thermo, CA), CD20 (L26; Ready-to-Use, Dako, CA), and CD3 (SP7; 1:150, Thermo, CA) was negative in the plasmacytoid cells (Fig. 2D). Immunocytochemical staining for immunoglobulin light chain lambda (HP6054; 1:200, Thermo, CA) and kappa (L1C1; 1:200, Thermo, CA) was positive exclusively for the lambda light chain (Fig. 2C).
Histopatholologic and Immunohistochemical Findings Examination of the surgical specimen revealed a 1.3 3 1.0 3 0.9 cm3 well-circumscribed, reddish-brown mass along with multiple hyperplastic nodules in the mid portion of the right thyroid (Fig. 3A). Histologic examination showed a partly infiltrative tumor nodule, which was separated from the surrounding thyroid by a thin fibrous capsule against a background of multiple hyperplastic nodules with Hashimoto thyroiditis (Fig. 3B). The tumor itself consisted of round to polygonal plasma cells with mild to moderate pleomorphism (Fig. 3C). The typical features of plasma cells (eccentrically located nuclei, coarse chromatin patterns, and perinuclear halos) were
well represented in the tumor cells. The results of imunohistochemical analysis of the histologic sections were similar to those of analyses using the cell block method. Together, these findings confirmed a diagnosis of thyroidal SEP.
Discussion SEP in the thyroid most commonly occurs in patients who have a history of Hashimoto thyroiditis.12 Regional recurrence is noted in less than 10% of patients. Approximately 70% of patients remain free of disease 10 years after treatment.13 The therapeutic approach for SEP is quite different from therapeutic approaches for other, more common types of follicular or parafollicular cellderived thyroid tumors. Early detection and accurate diagnosis are highly desirable, increasing the likelihood of timely, appropriate treatment for thyroidal SEP. FNAB is an effective, minimally invasive primary diagnostic method for evaluating thyroid nodules.14 However, in the case of rare tumors that may be unfamiliar to cytopathologists, FNAB results can generate substantial confusion. Additionally, the diagnosis of SEP through cytologic examination may be more challenging for SEP in the thyroid than for SEP at other sites. In this case that we report, the results of initial FNAB using the liquid-based method supported a diagnosis of plasmacytoma, although more common thyroid malignancies were also considered. We observed several characteristic cytomorphologic features of plasmacytoma, including (1) a heterogeneous cellular arrangement with a combination of individually dispersed and clustered tumor cells, (2) eccentrically located nuclei, (3) round nuclei without irregular membranes or spindle features, (4) some binucleated cells, (5) relatively clumped chromatin with numerous inconspicuous small nucleoli, (6) perinuclear halos, and (7) the absence of naked nuclei and Diagnostic Cytopathology, Vol. 42, No 11
967
Diagnostic Cytopathology DOI 10.1002/dc
LEE ET AL.
intranuclear pseudoinclusion. These cytomorphologic features are common to other tumor types including metastatic malignancies such as melanoma and metastatic poorly differentiated carcinomas as well as primary thyroid neoplasms. Among these tumors, medullary thyroid carcinoma and Hurthle cell neoplasm of the thyroid are the main differential diagnoses. The cytologic findings in this case were distinguished from those of previous studies by the combination of dispersed single cells and loosely cohesive aggregates of tumor cells. In a case of SEP described by Bourtsos et al., tumor cell aggregates were not abundant.11 Using the conventional smear, the author mainly observed dispersed cells.11 On the basis of our experience, we attribute these differences in cytomorphology to the use of different fixatives and to technical differences between conventional smear processing and liquid-based preparation.2,4,5 During the process of SurePath preparation, the pellet of aspirate is centrifuged and vortexed; however, cell clusters are well-preserved, with more cohesive and overlapped three-dimensional configurations.4 Because plasmacytoma is a hematologic malignancy, we believe that a smearing approach results in additional isolated cells with non-cohesive characteristics, whereas a liquidbased preparation retains the cell clusters. On aspiration cytology of medullary thyroid carcinomas, tumor cells are seen in the form of a combination of dispersed and loosely cohesive groups in approximately 29% of cases.15 Additionally, abundant granular cytoplasm and plasmacytoid appearance (including binucleation or eccentrically located nuclei) are commonly found in medullary thyroid carcinomas.16,17 In contrast, spindle-shaped tumor cells and long cytoplasmic processes are rarely found in plasmacytoma, even though they are observed in up to 50% of medullary thyroid carcinomas.11 In the case that we report, we did not identify spindle-shaped cells with long cytoplasmic processes. On using the liquid-based preparation, we observed well-defined and hyalinized perinuclear cytoplasmic vacuoles. However, no intranuclear inclusions were detected. With regard to vacuoles and hyaline inclusions, perinuclear cytoplasmic vacuoles (Russell bodies) are more frequently found in SEP than in medullary thyroid carcinoma.11,17 In contrast, intranuclear inclusions are more frequently found in medullary thyroid carcinoma,15 even though intranuclear inclusions known as “Dutcher bodies” can be found in plasmacytoma.11,15,16 In the present case of SEP, nuclei were predominantly round with coarse chromatin and numerous inconspicuous nucleoli. Previous studies have described the appearance of chromatin as granular in 65% of medullary thyroid carcinomas,15 in contrast to the moderately coarse appearance of chromatin in plasmacytoma.11 Follicular neoplasm of the Hurthle cell type shares prominent cytomorphologic patterns with plasmacytoma, 968
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including discohesive aggregates of tumor cells that are accompanied by dispersed single cells, tumor cells with abundant cytoplasm, eccentrically placed nuclei, and occasional multinucleation.18,19 However, in the case reported here, we did not note the key cytologic features that contribute to a diagnosis of a Hurthle cell neoplasm; marked nuclear pleomorphism and prominent macronucleoli were both absent.20,21 In conclusion, we have described a case of SEP in the thyroid gland, which was diagnosed using a liquid-based preparation of a FNAB sample. When presented with FNA cytology of a thyroid nodule that predominantly includes plasmacytoid cells, cytopathologists should consider the possibility of plasmacytoma. Although it can be difficult to differentiate plasmacytoma from other lesions, accurate diagnoses can be made on the basis of detailed observation of cytologic details, supported by immunocytochemistry findings.
References 1. Wiltshaw E. The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis. Medicine (Baltimore) 1976;55:217–238. 2. Fadda G, Rossi ED. Liquid-based cytology in fine-needle aspiration biopsies of the thyroid gland. Acta Cytol 2011;55:389–400. 3. Rossi ED, Raffaelli M, Zannoni GF, et al. Diagnostic efficacy of conventional as compared to liquid-based cytology in thyroid lesions: evaluation of 10,360 fine needle aspiration cytology cases. Acta Cytol 2009;53:659–666. 4. Hoda RS. Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts. Diagn Cytopathol 2007;35:621–634. 5. Jung CK, Lee A, Jung ES, et al. Split sample comparison of a liquid-based method and conventional smears in thyroid fine needle aspiration. Acta Cytol 2008;52:313–319. 6. Goel G, Rai S, Naik R, et al. Cytodiagnosis of extramedullary plasmacytomas. Acta Cytol 2010;54:255–258. 7. Bangerter M, Hildebrand A, Waidmann O, et al. Fine needle aspiration cytology in extramedullary plasmacytoma. Acta Cytol 2000;44: 287–291. 8. Pai RR, Raghuveer CV. Extramedullary plasmacytoma diagnosed by fine needle aspiration cytology. A report of four cases. Acta Cytol 1996;40:963–966. 9. Rege JD, Aditya GS, Shet TM. Fine needle aspiration cytology of extramedullary plasmacytoma. Acta Cytol 2002;46:789–790. 10. Vailati A, Marena C, Milani F, et al. Cytological evidence of plasmacytoma of the thyroid. Haematologica 1995;80:91–92. 11. Bourtsos EP, Bedrossian CW, De Frias DV, et al. Thyroid plasmacytoma mimicking medullary carcinoma: a potential pitfall in aspiration cytology. Diagn Cytopathol 2000;23:354–358. 12. Kovacs CS, Mant MJ, Nguyen GK, et al. Plasma cell lesions of the thyroid: report of a case of solitary plasmacytoma and a review of the literature. Thyroid 1994;4:65–71. 13. Dimopoulos MA, Hamilos G. Solitary bone plasmacytoma and extramedullary plasmacytoma. Curr Treat Options Oncol 2002;3: 255–259. 14. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993;328:553–559.
Diagnostic Cytopathology DOI 10.1002/dc
SOLITARY EXTRAMEDULLARY PLASMACYTOMA OF THE THYROID 15. Forrest CH, Frost FA, de Boer WB, et al. Medullary carcinoma of the thyroid: accuracy of diagnosis of fine-needle aspiration cytology. Cancer 1998;84:295–302. 16. Das DK, Gupta SK, Sehgal S. Extramedullary plasma cell tumors: Diagnosis by fine-needle aspiration cytology. Diagn Cytopathol 1986;2:248–251. 17. Pitman MB, Oertel YC, Geisinger KR. Medullary thyroid carcinoma. In: Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. New York: Springer; 2010. p 118–125. 18. Faquin WC, Michael CW, Renshaw AA, et al. Follicular neoplasm, Hurthle cell type/Suspicious for a follicular neoplasm, Hurthle cell
type. In: Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. New York: Springer; 2010. p 59–73. 19. Vodanovic S, Crepinko I, Smoje J. Morphologic diagnosis of Hurthle cell tumors of the thyroid gland. Acta Cytol 1993;37:317– 322. 20. Kini SR, Miller JM, Hamburger JI. Cytopathology of Hurthle cell lesions of the thyroid gland by fine needle aspiration. Acta Cytol 1981;25:647–652. 21. Gonzalez JL, Wang HH, Ducatman BS. Fine-needle aspiration of Hurthle cell lesions. A cytomorphologic approach to diagnosis. Am J Clin Pathol 1993;100:231–235.
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Preoperative cytologic diagnosis of solitary extramedullary plasmacytoma (SEP) presents a challenge to cytopathologists because this tumor rarely occurs as a primary thyroid malignant neoplasm. In this report, we provide the first description of liquid-based cytomorphologic findings of SEP observed on fineneedle aspiration biopsy (FNAB) of the thyroid. A 56-year-old woman with a history of Hashimoto thyroiditis presented with a growing nodule in the thyroid. The liquid-based preparation obtained from FNAB showed numerous dispersed plasmacytoid cells with occasional loosely cohesive aggregates of tumor cells. Cells were round to oval in shape, with eccentrically located nuclei. Hyalinized perinuclear vacuoles were found in the cytoplasm of the tumor cells. Initial cytological findings, including those of immunochemistry using a cell block preparation, were consistent with plasmacytoma. Histopathological examination subsequent to thyroidectomy revealed a plasmacytoma in the thyroid. Plasma cell neoplasms were not concurrently detected in tissues other than the thyroid. On the basis of preoperative FNAB findings, a specific diagnosis of SEP in the thyroid can be difficult because this tumor is rare. Moreover, diagnosis is impeded because SEP in the thyroid resembles other, more common thyroid lesions, including both benign and malignant neoplasms. Careful cytomorphologic examination and supportive studies may be required to fully confirm a diagnosis of SEP. Diagn. Cytopathol. 2014;42:964–969. VC 2014 Wiley Periodicals, Inc. 1 Department of Pathology, Chung-Ang University Hospital, ChungAng University College of Medicine, Seoul, South Korea 2 Department of Pathology, Samsung Medical Center, Seoul, South Korea 3 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea *Correspondence to: Han Suk Ryu, M.D., Ph.D., Department of Pathology, Seoul National University Hospital, 28 Yongon-dong, Jongro-gu Seoul 110-799, Seoul, South Korea. E-mail: [email protected] Received 5 February 2013; Revised 16 September 2013; Accepted 3 December 2013 DOI: 10.1002/dc.23086 Published online 13 March 2014 in Wiley Online Library (wileyonlinelibrary.com).
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Key Words: extramedullary plasmacytoma; thyroid; fine-needle aspiration; liquid-based preparation
Solitary extramedullary plasmacytoma (SEP) most commonly occurs in the head and neck region, primarily in the upper respiratory tract.1 Thyroidal SEP is rare, and the cytomorphologic findings are not clearly differentiated from those of other, more common thyroid tumors, both benign and malignant. Therefore, diagnosis of thyroidal SEP on the basis of fine-needle aspiration biopsy (FNAB) findings is challenging. Recently, liquid-based cytology has gained favor as an alternative preparation method to the conventional smear for FNAB analyses.2,3 However, the cytologic features of thyroid lesions could substantially differ depending on the method of preparation (liquid-based or conventional).4,5 Although a few studies have reported the cytomorphologic findings associated with SEP, to our knowledge, no publications have discussed the liquid-based cytologic findings of SEP.6–9 Additionally, the aspiration cytology findings of thyroidal SEP have only been discussed in a few prior reports.10,11 Here, we present the first case report of thyroidal SEP diagnosed by FNA cytology performed using a liquid-based method.
Case Report A 56-year-old woman with a 2-year history of Hashimoto’s thyroiditis presented with a growing, palpable thyroid nodule. She was clinically euthyroid; thyroid function test results were within normal limits, with the exception of the serum thyroglobulin level, which was elevated at 457.7 ng/mL (reference range: 2.0–70.0 ng/mL). C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
SOLITARY EXTRAMEDULLARY PLASMACYTOMA OF THE THYROID
Fig. 1. Cytopathologic findings. A: Tumor cell clusters and individually dispersed tumor cells against a clear background (Papanicolaou stain, 2003) with cohesive aggregates of tumor cells. B: A representative feature of cohesive clusters of plasmacytoma (Papanicolaou stain, 1,0003). C: Binucleated tumor cells are apparent at the center. Abundant granular cytoplasm and eccentrically located nuclei are reminiscent of medullary carcinoma and Hurthle cell neoplasm. Tumor cells show clumped chromatin with inconspicuous small nucleoli and perinuclear halo (Papanicolaou stain, 1,0003). D: Tumor cell aggregates. Irregularity of nuclear membrane, pseudoinclusion, and spindle-shaped cells are absent (Papanicolaou stain, 1,0003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Neck ultrasonography revealed a 1.3-cm thyroid nodule that had grown since the patient’s last examination, as well as multiple, apparently stable cystic nodules. Ultrasonography-guided FNAB was performed on the growing thyroid nodule. The FNAB samples were submitted for processing and liquid-based cytology slides were prepared according to SurePathTM (Becton Dickinson Diagnostics-TriPath, Burlington, NC) protocols. The cytologic results were suggestive of plasmacytoma. Long bone radiography revealed no evidence of tumor involvement in the form of multiple myeloma. Complete
blood cell count results and peripheral blood cell morphology analysis were within normal limits. Serum calcium and potassium levels were also unremarkable. Monoclonal immunoglobulin was not detected in serum and urine samples. Histological analysis of bone marrow aspirate indicated normal architecture. Two weeks after FNAB, total thyroidectomy was performed. To date, there is no evidence of progression to multiple myeloma on the basis of bone marrow needle biopsy findings, serum test results for M proteins, and urine test results for M proteins. Diagnostic Cytopathology, Vol. 42, No 11
965
Diagnostic Cytopathology DOI 10.1002/dc
LEE ET AL.
Fig. 2. Immunocytochemical staining of a cell block preparation. Tumor cells show (A) strong membrane staining for CD138, as well as strong expression of (B) CD79a and (C) the lambda light chain. Tumor cells do not show expression of (D) CD20 (A–D, 4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Cytologic and Immunocytochemical Findings The FNAB liquid-based preparation comprised several tumor cell clusters and individually dispersed tumor cells against a clear background, with occasional colloid materials (Fig. 1A). The cells were round to ovoid in appearance with abundant granular cytoplasm and occasional perinuclear clearing. Round nuclei were eccentrically located, and no nuclear membrane irregularity was noted. Binucleated cells were occasionally present. The chromatin was coarsely clumped with small single or multiple nucleoli (Figs. 1B–D). No nuclear pseudoinclusions were 966
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found. Immunocytochemical staining was performed, using the cell block technique. Paraffin-embedded samples were sliced at a thickness of 4 lm, and each section was prepared for immunocytochemical detection. For heat-induced epitope retrieval, the sections were processed with Tris-EDTA (pH 9.0) solution for 20 min, after being de-waxed with xylene and rehydrated using a graded series of ethanol. Sections were then incubated in a peroxidase blocking solution (3% H2O2) for 10 min at room temperature, and primary antibodies were added. Subsequently, the secondary antibody was added, sections
Diagnostic Cytopathology DOI 10.1002/dc
SOLITARY EXTRAMEDULLARY PLASMACYTOMA OF THE THYROID
Fig. 3. Gross and histopathologic findings. A: Gross examination reveals a well-demarcated, reddish-brown tumor, located between two hyperplastic nodules. B: Low-power view (hematoxylin and eosin stain, 12.53) shows the encapsulated tumor nodule against a background of hyperplastic nodules with lymphocytic infiltration. C: The tumor is composed of round to polygonal plasma cells with mild to moderate pleomorphism (hematoxylin and eosin stain, 4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
were counterstained with Mayer’s hematoxylin, and the reaction was visualized using diaminobenzidine. Additional immunohistochemical staining was performed on a laryngeal plasmacytoma (as a positive control) and a papillary thyroid carcinoma (as a negative control). Immunocytochemical staining for leukocyte common antigen (2B11 (1) 1 PD7/26 (1); Ready-to-Use, Dako, CA), CD138 (Syndecan-1; 1:50, Bio SB, CA), and CD79a (SP18; 1:100, Thermo, CA) was strongly positive in plasmacytoid cells (Figs. 2A and B). However, immunocytochemical staining for pan-cytokeratin (AE1/AE3; 1:300, Thermo, CA), thyroid transcription factor-1 (SPT24; 1:100, Leica, Newcastle, UK), thyroglobulin (TGB04 (2H11) 1 TGB05 (6E1); 1:500, Thermo, CA), calcitonin (SP17; 1:100, Thermo, CA), CD20 (L26; Ready-to-Use, Dako, CA), and CD3 (SP7; 1:150, Thermo, CA) was negative in the plasmacytoid cells (Fig. 2D). Immunocytochemical staining for immunoglobulin light chain lambda (HP6054; 1:200, Thermo, CA) and kappa (L1C1; 1:200, Thermo, CA) was positive exclusively for the lambda light chain (Fig. 2C).
Histopatholologic and Immunohistochemical Findings Examination of the surgical specimen revealed a 1.3 3 1.0 3 0.9 cm3 well-circumscribed, reddish-brown mass along with multiple hyperplastic nodules in the mid portion of the right thyroid (Fig. 3A). Histologic examination showed a partly infiltrative tumor nodule, which was separated from the surrounding thyroid by a thin fibrous capsule against a background of multiple hyperplastic nodules with Hashimoto thyroiditis (Fig. 3B). The tumor itself consisted of round to polygonal plasma cells with mild to moderate pleomorphism (Fig. 3C). The typical features of plasma cells (eccentrically located nuclei, coarse chromatin patterns, and perinuclear halos) were
well represented in the tumor cells. The results of imunohistochemical analysis of the histologic sections were similar to those of analyses using the cell block method. Together, these findings confirmed a diagnosis of thyroidal SEP.
Discussion SEP in the thyroid most commonly occurs in patients who have a history of Hashimoto thyroiditis.12 Regional recurrence is noted in less than 10% of patients. Approximately 70% of patients remain free of disease 10 years after treatment.13 The therapeutic approach for SEP is quite different from therapeutic approaches for other, more common types of follicular or parafollicular cellderived thyroid tumors. Early detection and accurate diagnosis are highly desirable, increasing the likelihood of timely, appropriate treatment for thyroidal SEP. FNAB is an effective, minimally invasive primary diagnostic method for evaluating thyroid nodules.14 However, in the case of rare tumors that may be unfamiliar to cytopathologists, FNAB results can generate substantial confusion. Additionally, the diagnosis of SEP through cytologic examination may be more challenging for SEP in the thyroid than for SEP at other sites. In this case that we report, the results of initial FNAB using the liquid-based method supported a diagnosis of plasmacytoma, although more common thyroid malignancies were also considered. We observed several characteristic cytomorphologic features of plasmacytoma, including (1) a heterogeneous cellular arrangement with a combination of individually dispersed and clustered tumor cells, (2) eccentrically located nuclei, (3) round nuclei without irregular membranes or spindle features, (4) some binucleated cells, (5) relatively clumped chromatin with numerous inconspicuous small nucleoli, (6) perinuclear halos, and (7) the absence of naked nuclei and Diagnostic Cytopathology, Vol. 42, No 11
967
Diagnostic Cytopathology DOI 10.1002/dc
LEE ET AL.
intranuclear pseudoinclusion. These cytomorphologic features are common to other tumor types including metastatic malignancies such as melanoma and metastatic poorly differentiated carcinomas as well as primary thyroid neoplasms. Among these tumors, medullary thyroid carcinoma and Hurthle cell neoplasm of the thyroid are the main differential diagnoses. The cytologic findings in this case were distinguished from those of previous studies by the combination of dispersed single cells and loosely cohesive aggregates of tumor cells. In a case of SEP described by Bourtsos et al., tumor cell aggregates were not abundant.11 Using the conventional smear, the author mainly observed dispersed cells.11 On the basis of our experience, we attribute these differences in cytomorphology to the use of different fixatives and to technical differences between conventional smear processing and liquid-based preparation.2,4,5 During the process of SurePath preparation, the pellet of aspirate is centrifuged and vortexed; however, cell clusters are well-preserved, with more cohesive and overlapped three-dimensional configurations.4 Because plasmacytoma is a hematologic malignancy, we believe that a smearing approach results in additional isolated cells with non-cohesive characteristics, whereas a liquidbased preparation retains the cell clusters. On aspiration cytology of medullary thyroid carcinomas, tumor cells are seen in the form of a combination of dispersed and loosely cohesive groups in approximately 29% of cases.15 Additionally, abundant granular cytoplasm and plasmacytoid appearance (including binucleation or eccentrically located nuclei) are commonly found in medullary thyroid carcinomas.16,17 In contrast, spindle-shaped tumor cells and long cytoplasmic processes are rarely found in plasmacytoma, even though they are observed in up to 50% of medullary thyroid carcinomas.11 In the case that we report, we did not identify spindle-shaped cells with long cytoplasmic processes. On using the liquid-based preparation, we observed well-defined and hyalinized perinuclear cytoplasmic vacuoles. However, no intranuclear inclusions were detected. With regard to vacuoles and hyaline inclusions, perinuclear cytoplasmic vacuoles (Russell bodies) are more frequently found in SEP than in medullary thyroid carcinoma.11,17 In contrast, intranuclear inclusions are more frequently found in medullary thyroid carcinoma,15 even though intranuclear inclusions known as “Dutcher bodies” can be found in plasmacytoma.11,15,16 In the present case of SEP, nuclei were predominantly round with coarse chromatin and numerous inconspicuous nucleoli. Previous studies have described the appearance of chromatin as granular in 65% of medullary thyroid carcinomas,15 in contrast to the moderately coarse appearance of chromatin in plasmacytoma.11 Follicular neoplasm of the Hurthle cell type shares prominent cytomorphologic patterns with plasmacytoma, 968
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including discohesive aggregates of tumor cells that are accompanied by dispersed single cells, tumor cells with abundant cytoplasm, eccentrically placed nuclei, and occasional multinucleation.18,19 However, in the case reported here, we did not note the key cytologic features that contribute to a diagnosis of a Hurthle cell neoplasm; marked nuclear pleomorphism and prominent macronucleoli were both absent.20,21 In conclusion, we have described a case of SEP in the thyroid gland, which was diagnosed using a liquid-based preparation of a FNAB sample. When presented with FNA cytology of a thyroid nodule that predominantly includes plasmacytoid cells, cytopathologists should consider the possibility of plasmacytoma. Although it can be difficult to differentiate plasmacytoma from other lesions, accurate diagnoses can be made on the basis of detailed observation of cytologic details, supported by immunocytochemistry findings.
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Diagnostic Cytopathology DOI 10.1002/dc
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type. In: Ali SZ, Cibas ES, editors. The Bethesda system for reporting thyroid cytopathology. New York: Springer; 2010. p 59–73. 19. Vodanovic S, Crepinko I, Smoje J. Morphologic diagnosis of Hurthle cell tumors of the thyroid gland. Acta Cytol 1993;37:317– 322. 20. Kini SR, Miller JM, Hamburger JI. Cytopathology of Hurthle cell lesions of the thyroid gland by fine needle aspiration. Acta Cytol 1981;25:647–652. 21. Gonzalez JL, Wang HH, Ducatman BS. Fine-needle aspiration of Hurthle cell lesions. A cytomorphologic approach to diagnosis. Am J Clin Pathol 1993;100:231–235.
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