|Year : 2020 | Volume
| Issue : 2 | Page : 75-79
A case report of thyroid plasmacytoma and literature update
Fahd Refai1, Wafaey Gomaa2, Layla Abdullah1
1 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pathology, Faculty of Medicine, Minia University, Al Minia, Egypt
|Date of Submission||18-Jul-2019|
|Date of Acceptance||13-Sep-2019|
|Date of Web Publication||08-Nov-2019|
Prof. Wafaey Gomaa
Department of Pathology, Faculty of Medicine, King Abdulaziz University,
P.O. Box: 80205, Jeddah 21589, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Plasmacytomas of the thyroid gland are rare, whether or not they arise as solitary (primary) lesions or secondary to systemic multiple myeloma. Here, we present the case of a 71-year-old female presenting with goiter and Hashimoto's thyroiditis, in whom the subsequent histopathological diagnosis of plasmacytoma was a surprise. In presenting this case, we summarize the last 25 years of literature on thyroid plasmacytoma and review the salient clinicopathological characteristics, differential diagnoses, management, and outcomes of this rare condition.
Keywords: Extramedullary, pathology, plasmacytoma, thyroid
|How to cite this article:|
Refai F, Gomaa W, Abdullah L. A case report of thyroid plasmacytoma and literature update. J Microsc Ultrastruct 2020;8:75-9
|How to cite this URL:|
Refai F, Gomaa W, Abdullah L. A case report of thyroid plasmacytoma and literature update. J Microsc Ultrastruct [serial online] 2020 [cited 2020 Jun 5];8:75-9. Available from: http://www.jmau.org/text.asp?2020/8/2/75/270590
| Introduction|| |
Plasmacytoma can occur in the thyroid gland either as primary lesions (solitary extramedullary plasmacytoma [EMP]) or secondary to systemic spread of multiple myeloma. Differentiating between primary and secondary plasmacytoma is essential, because their clinical behavior and subsequent management are markedly different. Here, we describe a case of a thyroid plasmacytoma arising in a background of Hashimoto's thyroiditis. In doing so, we take the opportunity to emphasize the importance of clinical follow-up and review the last 25 years of literature on thyroid plasmacytoma including their clinicopathological features, important differential diagnoses, and outcomes.
| Case Presentation|| |
A 71-year-old female with a medical history of hypertension and diabetes presented with a massive goiter. Thyroid function tests on presentation revealed a thyroid-stimulating hormone (TSH) of 5.51 μIU/L (0.27–4.2), free T3 of 3.67 pmol/L (2.8–7), free T4 of 9.98 pmol/L (12–22), thyroid peroxidase antibody of 319 IU/mL (0–34), and thyroid thyroglobulin antibody of 683 IU/mL (0–115). A thyroid ultrasound showed enlarged (right lobe: 6.9 cm × 3.0 cm × 2.7 cm; left lobe: 7.4 cm × 3.1 cm × 3.8 cm; isthmus unremarkable) heterogeneous lobes bilaterally with prominent vasculature and microcalcifications, but no focal lesions. Scintigraphy was normal with homogeneous 1.7% Tc99m uptake. The laboratory and imaging findings were entirely consistent with autoimmune (Hashimoto's) thyroiditis. She underwent elective thyroidectomy 1 year later. The patient gave consent before surgery. The case is reported according to the regulations of Research Committee of the Biomedical Ethics Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. At that time, her TSH had risen to 11.0 μIU/L (0.27–4.2), but her free T4 levels were static at 9.84 pmol/L (12–22). Her operation was unremarkable, and she was discharged without any hoarseness of voice, but with low calcium level (1.95 mmol/L [2.12–2.52]) and hypoalbuminemia (25 g/L [40.2–47.6]). An intraoperative frozen section revealed chronic thyroiditis with a prominent plasma cell component.
On macroscopic pathological examination, the left lobe measured 9 cm × 6 cm × 3.5 cm and the right lobe measured 10 cm × 6 cm × 3.5 cm, both with prominent capsular blood vessels, gray-yellow in color, and firm in consistency [Figure 1]a and [Figure 1]b. Microscopic examination [Figure 1]c and [Figure 1]d revealed a diffuse, mature plasma cell infiltrate separated by fibrous septa. Occasional binucleation and mitotic figures were visible, along with focal lymphoid follicle formation and germinal centers. Residual thyroid follicles were present with oncocytic follicular lining. On immunohistochemical testing, the lesion was positive for antibodies targeting kappa light chain, CD38, and CD45, but negative for lambda light chain, CD138, thyroglobulin, CD20, synaptophysin, chromogranin, NSE, CD30, calcitonin, and Bcl-2 [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. There was no evidence of follicular or papillary carcinoma. These histological features were consistent with EMP in a background of focal Hashimoto's thyroiditis. A thorough neck examination and serum and protein electrophoresis were recommended to rule out neck extension and multiple myeloma, respectively. Unfortunately, the patient moved shortly after the operation and was lost to follow-up.
|Figure 1: Gross and microscopic appearance, (a) The left lobe is shown and measures 9 cm. (b) The cut surface is gray-yellow in color. (c) Diffuse infiltration with mature plasma cell infiltrate separated by fibrous septa along with focal lymphoid follicle formation and germinal center (H and E 40×). (d) Sheet of diffuse mature plasma (H and E 200×)|
Click here to view
|Figure 2: Immunohistochemistry, (a) Tumor cells show positive membranous reaction to CD45 (leukocyte common antigen). (b) Tumor cells show positive membranous reaction to CD38. (c) Tumor cells show positive cytoplasmic membranous reaction to kappa. (d) Tumor cells show negative reaction to lambda. Original magnification is 100×. DAB (3,3'-diaminobenzidine) was used as chromogen and hematoxylin as the counter stain|
Click here to view
| Discussion|| |
Here, we report a case of plasmacytoma of the thyroid, which, to the best of our knowledge, is only the second to be reported in a Saudi Arabian individual. Plasmacytoma of the thyroid can be either primary or secondary to systemic spread of multiple myeloma. Primary EMPs fall into the spectrum of plasma cell neoplasms, but account for only 3%–5% of total, usually arising in the head and neck region (80%–90%), but rarely at other sites. This includes the thyroid where, since first being described by Voegt in 1938, only a few cases have been described. Although the exact incidence of thyroid EMP is difficult to establish due to its rarity, early large attempts to quantify thyroid EMP revealed seven thyroid cases in 272 (3%) EMPs, and conversely, Hazard and Schildecker found only two EMPs in 14,000 thyroid operations. In their effort to summarize the literature on thyroid plasma cell neoplasms in 1994, Kovacs et al. collated 50 cases of solitary EMP of the thyroid and 16 cases of thyroid involvement with systemic multiple myeloma. In a similar effort, but including the Japanese literature, Ohshima et al. identified 34 cases of solitary thyroid EMP in the Western literature and further 32 cases in the Japanese literature. Since then, further 19 cases of solitary EMP of the thyroid [Table 1] and 11 cases of thyroid EMP with multiple myeloma [Table 2] have been reported as case reports in the English literature.
|Table 1: Cases of solitary extramedullary plasmacytoma of the thyroid reported since 1994|
Click here to view
|Table 2: Cases of thyroid involvement with multiple myeloma reported since 1994|
Click here to view
Similar to Kovacs et al., we found that there was a female predominance of primary EMP of the thyroid (63% vs. 61% in Kovacs et al.) and average age of presentation in the sixth to seventh decade (58 [±14] vs. 63.6 years in Kovacs et al.).
Plasma cells are an unusual finding in the thyroid, with the frozen section plasmacytosis raising early suspicion of an unusual entity in this case. The diffuse involvement of the thyroid with plasma cells, normal scintigraphy, and no evidence of a focal lesion are commonly reported, so our case is not unusual in that regard. The morphological features and CD38 positivity with kappa light chain restriction made the diagnosis relatively straightforward. However, the diagnosis is not always straightforward. The main histopathological differential diagnoses are mucosa-associated lymphoid tissue (MALT) lymphoma (especially with marked plasma cell differentiation),, lymphoplasmacytic lymphoma, large B cell lymphoma with plasmo/immunoblastic differentiation, medullary carcinoma,, and plasma cell granuloma, so both morphological and immunohistochemical features must be considered in addition to a high index of suspicion for EMP. Here, there was no CD20 positivity and lymphoepithelial complexes were absent, This ruled out MALT lymphoma. On the other hand, the relatively low proliferation rate and nuclear atypia did not suggest an aggressive B cell lymphoma. Calcitonin and neuroendocrine markers were negative, ruling out medullary carcinoma, and the kappa light chain restriction was inconsistent with plasma cell granuloma. However, particular care must be taken when making a cytological diagnosis on fine needle aspirates, because the presence of mimicking nuclear atypia and amyloid, the stromal amyloid of medullary carcinoma and the light chain deposits of plasmacytoma being identical, can prompt a misdiagnosis of medullary carcinoma., The distinction between EMP and medullary thyroid carcinoma is important because the management is different. Medullary thyroid carcinoma is usually treated by thyroidectomy and neck dissection rather than thyroidectomy/radiotherapy alone. Further, follicular neoplasm of the Hürthle cell type shares prominent cytomorphological patterns with plasmacytoma including discohesive aggregates of tumor cells accompanied by dispersed single cells, tumor cells with abundant cytoplasm, eccentrically placed nuclei, and occasional multinucleation, so should be considered when examining cytological preparations.
Regrettably in this case, the patient was lost to follow-up, and despite the clinical recommendation to screen for multiple myeloma, this could not be performed; about a third of upper respiratory tract EMP have systemic spread on further examination, and many of the case reports of thyroid EMP are subsequently found to have systemic involvement. In their comprehensive analysis of outcomes of 46 EMP at different sites (albeit only one confined to the thyroid), Galeini et al. established specific diagnostic criteria for primary (localized) EMP: (i) monoclonal plasma cell histology on tissue biopsy, (ii) plasma cells in the bone marrow representing <5% of all nucleated cells, (iii) absence of lytic skeletal lesions or other tissue involvement, (iv) a lack of hypocalcaemia or renal failure, and (v) a low level of serum M protein, if present. We were unable to establish whether this lesion was localized or part of a systemic manifestation of multiple myeloma. However, given that there was concomitant Hashimoto's thyroiditis, which to our knowledge has yet to be reported in 13 thyroid cases of multiple myeloma in Kovacs et al. or in the further 11 multiple myeloma cases summarized in [Table 2], it is much more likely that this case represents a primary EMP without systemic spread. Conversely, 36/44 (82%) of primary EMPs in Kovacs et al. and 10/19 (53%) of primary EMPs summarized in [Table 1] arose in a background of Hashimoto's thyroiditis, and further investigations are warranted to establish whether the autoimmune or chronic inflammatory process is causative for primary EMP as suggested for other lymphomas and papillary carcinoma.
Although there is no major consensus on the optimal treatment for primary EMP, both surgery and radiotherapy alone or in combination have frequently been used to manage the disease; indeed, all the newly reviewed cases in [Table 1] were successfully treated with either or both modalities. Accordingly, surgery in our case was appropriate in this case. Further systemic chemotherapy would have been warranted if the lesion had manifestations of systemic disease. Clinical outcomes for patients with localized disease are extremely good. In contrast to solitary plasmacytoma of the bone, which frequently converts into multiple myeloma, EMP remains localized, with 83% showing no evidence of disease after a mean follow-up of 56 months in Kovacs et al. and only 3/50 patients progressing to multiple myeloma during follow-up. Likewise, when considering all EMPs, they have a favorable prognosis (15 years survival rate of 78%) when treated locally by irradiation and/or surgery. Of our 19 new cases summarized in [Table 1], there were no recurrences or deaths from the disease, albeit with only short follow-up periods. By contrast, nearly half of all patients with plasmacytoma occurring in the context of multiple myeloma died of their disease with a mean survival of 9.7 ± 15.7 months and further 33% had persistent disease.
In conclusion, primary and secondary plasmacytomas are rare thyroid neoplasms that are often unexpected, and in the case of primary plasmacytoma, are often associated with Hashimoto's thyroiditis. Clinical examination and imaging are generally unhelpful in diagnosis, and care must be taken with pathological assessment, particularly when interpreting cytology samples. Follow-up is essential, because primary and secondary lesions have markedly different management and outcomes. Finally, further research is required to establish the relationship between inflammatory thyroid disease and the development of primary EMP.
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kovacs CS, Mant MJ, Nguyen GK, Ginsberg J. Plasma cell lesions of the thyroid: Report of a case of solitary plasmacytoma and a review of the literature. Thyroid 1994;4:65-71.
Meccawy AA. Plasmacytoma of the thyroid gland: Case report and review of the literature. J King Abdulaziz Univer Med Sci 2010;98:1-20.
McKenna R, Kyle R, Kuehl W, Grogan T, Harris N, Coupland R, et al
. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Plasma Cell Neoplasms. Lyon: IARC; 2008. p. 200-13.
Alexiou C, Kau RJ, Dietzfelbinger H, Kremer M, Spiess JC, Schratzenstaller B, et al.
Extramedullary plasmacytoma: Tumor occurrence and therapeutic concepts. Cancer 1999;85:2305-14.
Voegt H. Extramedullare plasmocytoma. Virchows Arch 1938;302:497-508.
Wiltshaw E. The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis. Medicine (Baltimore) 1976;55:217-38.
Hazard J, Schildecker W. Plasmocytoma of the thyroid. Am J Pathol 1949;25:819-20.
Ohshima M, Momiyama T, Souda S, Kuratani T, Toda K, Hiasa Y. Primary plasmacytoma of the thyroid: A case report and comparative literature study between Western Nations and Japan. Pathol Int 1994;44:645-51.
Hassan MJ, Khans S, Pujani M, Jetley S, Raina PK, Ahmad R. Extramedullary plasmacytoma of the thyroid: Report of a rare case. Blood Res 2014;49:280-3.
Mertens de Wilmars M, Knoops L, Sempoux C, Galant C, Geets X, Poirel HA, et al.
Solitary extramedullary plasmocytoma of the thyroid: A case report and histological approach to plasma cells infiltrate in the thyroid gland. Acta Clin Belg 2015;70:133-7.
Bhat V, Shariff S, Reddy RA. Extramedullary plasmacytoma of thyroid-a mimicker of medullary carcinoma at fine needle aspiration cytology: A case report. J Cytol 2014;31:53-6.
] [Full text]
Lee CH, Jung YY, Chung YR, Ryu HS. Liquid-based cytologic findings of solitary extramedullary plasmacytoma in thyroid: A case report identified with fine-needle aspiration cytology. Diagn Cytopathol 2014;42:964-9.
Ridal M, Ouattassi N, Harmouch T, Amarti A, Alami MN. Solitary extramedullary plasmacytoma of the thyroid gland. Case Rep Otolaryngol 2012;2012:282784.
Yao CM, Erovic B, Higgins KM. Solitary extramedullary plasmacytomas of the thyroid in Hashimoto's thyroiditis. Thyroid 2012;22:861-2.
Puliga G, Olla L, Bellisano G, Di Naro N, Ganau M, Lai ML, et al.
Solitary extramedullary plasmacytoma of the thyroid gland associated with multinodular goiter: Case report and review of the literature. Pathologica 2011;103:61-3.
Patten DK, Fazel M, Dina R, Tolley N. Solitary extramedullary plasmacytoma of the thyroid involved by papillary carcinoma: A case report and review of the literature. Endocr Pathol 2011;22:155-8.
Shahani S, Ahmad A, Barakat FH, Chuang HH, Fowler NH, Myers JN, et al.
F-18 FDG PET/CT detecting thyroid plasmacytoma after the successful treatment of gastric large B-cell lymphoma. Clin Nucl Med 2011;36:317-9.
Abdel Khalek MS, Ibrahim WG, Crawford BE, Kandil EH. Euthyroid enlargement of the thyroid gland. Plasmacytoma in thyroid. Neth J Med 2010;68:424, 429.
Fraser SC, Bishop JA, Champaneri S, Tufano RP. Pathology quiz case 2: Extramedullary plasmacytoma (EMP). Arch Otolaryngol Head Neck Surg 2010;136:635, 636-7.
Avila A, Villalpando A, Montoya G, Luna MA. Clinical features and differential diagnoses of solitary extramedullary plasmacytoma of the thyroid: A case report. Ann Diagn Pathol 2009;13:119-23.
Ozkan E, Tokmak E, Kir KM. Detection of thyroid plasmacytoma by F-18 FDG PET/CT imaging. Clin Nucl Med 2008;33:292-3.
Chaganti S, Gurunathan R, McNaboe E. Solitary extramedullary plasmacytoma of the thyroid gland: A case report and review of literature. Internet J Head Neck Surg 2007;2:1-4.
Kuo SF, Chang HY, Hsueh C, Lin JD. Extramedullary plasmacytoma of the thyroid. N
Z Med J 2006;119:U2005.
De Schrijver I, Smeets P. Thyroid enlargement due to extramedullary plasmacytoma. JBR-BTR 2004;87:73-5.
Hasegawa Y, Itoh T, Tamagawa Y, Komeno T, Kojima H, Ninomiya H, et al.
Non-Hodgkin's lymphoma followed by plasmacytoma, both arising in A thyroid gland with Hashimoto's disease. Leuk Lymphoma 1999;35:613-8.
Sahu KK, Singh P, Malhotra P, Srinivasan R. Thyroid plasmacytoma: A rare cause of hoarseness of voice. Indian J Nucl Med 2019;34:78-80.
] [Full text]
Gochhait D, Govindarajalou R, Kar R, Rangarajan V, Dehuri P, Dubashi B. Plasmacytoma of thyroid clinically and morphologically mimicking primary thyroid carcinoma. Cytopathology 2019;30:113-6.
Singh K, Kumar P, Pruthy R, Goyal G. Multiple myeloma presenting as thyroid plasmacytoma. Indian J Med Paediatr Oncol 2017;38:552-4.
] [Full text]
Park BJ, Kalish RJ, Vercillo AP. Disseminated plasmacytoma of the thyroid. Ear Nose Throat J 2010;89:137-9.
Ozdemir E, Bayraktar M, Sökmensüer C, Kir KM, Kansu E. Late relapse of a light-chain myeloma as extramedullary plasmacytoma of the thyroid gland after second allogeneic stem-cell transplantation. Clin Transplant 2009;23:981-4.
Serefhanoglu S, Sayinalp N, Haznedaroglu IC, Goker H, Cetiner D, Aksu S, et al.
Extramedullary plasmacytomas of the thyroid and pericardium as initial presentation of multiple myeloma. Ann Hematol 2008;87:853-4.
Terrier B, Aouba A, Diop S, Clerc J, Vasiliu V, Munera Y, et al.
Thyroid gland plasmacytoma with a dramatic and persistent complete response under thalidomide and dexamethasone-associated treatment. Leuk Lymphoma 2006;47:1424-6.
Wahner-Roedler DL, Witzig TE, Loehrer LL, Kyle RA. Gamma-heavy chain disease: Review of 23 cases. Medicine (Baltimore) 2003;82:236-50.
Bourtsos EP, Bedrossian CW, De Frias DV, Nayar R. Thyroid plasmacytoma mimicking medullary carcinoma: A potential pitfall in aspiration cytology. Diagn Cytopathol 2000;23:354-8.
Schiller VL, Deutsch AL, Turner RR. Multiple myeloma presenting as extramedullary plasmacytoma of the thyroid, advanced grade II-III plasmablastic type. Skeletal Radiol 1995;24:314-6.
Vailati A, Marena C, Milani F, Aristia L, Sozzé E, Galenda P, et al.
Cytological evidence of plasmacytoma of the thyroid. Haematologica 1995;80:91-2.
Aihara H, Tsutsumi Y, Ishikawa H. Extramedullary plasmacytoma of the thyroid, associated with follicular colonization and stromal deposition of polytypic immunoglobulins and major histocompatibility antigens. Possible categorization in MALT lymphoma. Acta Pathol Jpn 1992;42:672-83.
Kojima M, Shimizu K, Shimizu K, Masawa N. Incidental MALT type lymphoma exhibiting prominent plasma cell differentiation associated with hashimoto's thyroiditis. A two case report. Head Neck Pathol 2009;3:27-30.
Patil PA, DeLellis RA. Plasma cell granuloma of the thyroid: Review of an uncommon entity. Arch Pathol Lab Med 2018;142:998-1005.
Ewing MR, Foote FW Jr. Plasma-cell tumors of the mouth and upper air passages. Cancer 1952;5:499-513.
Galieni P, Cavo M, Pulsoni A, Avvisati G, Bigazzi C, Neri S, et al
. Clinical outcome of extramedullary plasmacytoma. Haematologica 2000;85:47-51.
[Figure 1], [Figure 2]
[Table 1], [Table 2]