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CASE REPORT |
https://doi.org/10.5005/jp-journals-10088-11235 |
Exploring the Extraordinary: Unusual Hematopoietic Malignancies of Thyroid Gland
1,2Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh, India
3Department of Endocrine and Breast Surgery, King George’s Medical University, Lucknow, Uttar Pradesh, India
4,5Department of Endocrine Surgery, King George’s Medical University, Lucknow, Uttar Pradesh, India
Corresponding Author: Chanchal Rana, Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh, India, Phone: +91 9451250305, e-mail: chanchal11aug@yahoo.com
How to cite this article: Singh R, Rana C, Shreyamsa M, et al. Exploring the Extraordinary: Unusual Hematopoietic Malignancies of Thyroid Gland. Indian J Endoc Surg Res 2024;19(1):21–25.
Source of support: Nil
Conflict of interest: Dr Pooja Ramakant is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group.
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Received on: 15 April 2024; Accepted on: 07 May 2024; Published on: 17 June 2024
ABSTRACT
Thyroid disorders encompass a broad spectrum of pathological conditions, the majority of which are benign and also include autoimmune thyroiditis, multinodular goiter, and papillary thyroid carcinoma. However, some thyroid pathologies are unusual and pose diagnostic and management challenges. This study discusses the presentation, diagnostic challenges, and management of these rare presentations and tumors, as seen in our institution.
First patient with primary T-cell lymphoma of the thyroid, an exceedingly rare malignancy accounting for a minute fraction of thyroid neoplasms. Second patient highlights an uncommon case of solitary extramedullary plasmacytoma of the thyroid, constituting less than 1% of all extramedullary plasmacytomas. Third patient portrays Langerhans cell histiocytosis (LCH) of the thyroid, an unusual entity often presenting diagnostic complexities due to its rarity and association with other thyroid pathologies.
These cases emphasize the rarity of these thyroid pathologies and the need for a comprehensive approach to diagnosis and management. Tailored treatment strategies are necessary, taking into account the clinical presentation and extent of the disease. Due to the limited data available for these rare pathologies, further research and comprehensive reporting are crucial for refining our understanding and optimizing treatment strategies. In conclusion, these cases exemplify the diagnostic and management challenges posed by unusual thyroid pathologies and underscore the importance of accurate diagnosis and a multidisciplinary approach to manage these rare conditions effectively.
Keywords: Case report, Langerhans cell histiocytosis, Plasmacytoma, T-cell lymphoma, Thyroid diseases, Thyroid neoplasms.
INTRODUCTION
Rare diseases are entities affecting 5 or fewer per 10,000 (1 person per 2,000) with variable incidence/prevalence across regions.1 Another term, ultrarare diseases—refers to diseases that affect less than 1 person per 50,000.2 Approximately, 7,000 distinct rare entities, including those of the thyroid gland, have been described. Most are genetically determined and affect ~350 million people worldwide.1
Thyroid neoplasms are the most common endocrine malignancies. Still, they are apt to be classified as rare diseases as their incidence ranges from the more common follicular cell-derived lesions (papillary, follicular, Hürthle cell carcinomas) to the rare C-cell-derived medullary carcinomas. A few varieties of thyroid neoplasms are even more uncommon and encountered only occasionally in clinical practice. The diagnosis of these tumors is often made at the histologic level, with immunohistochemical stains necessary in some circumstances.3
This study aims to present our institutional experience in thyroid pathology, emphasizing certain less encountered/rare entities and the challenges faced during their cytological/histopathological evaluation and treatment.
CASE PRESENTATIONS
Case 1
A 48-year-old man presented with rapidly enlarging, painless swelling not associated with compressive symptoms, over the neck for 2 months that moved with deglutition. Clinical examination revealed a diffusely enlarged thyroid gland with a smooth surface, confirmed by ultrasonography. Complete blood count (CBC) and thyroid function tests (TFT) were within normal limits. Serum lactate dehydrogenase (LDH) was 683 IU/liter (105–333). Fine needle aspiration cytology (FNAC) smears were hypercellular, displaying a singly scattered population of medium-sized atypical cells with numerous lymphoglandular bodies in the background (Fig. 1A). The possibility of lymphoproliferative disorder was considered, and histopathological examination was advised for confirmation and typing by immunohistochemical analysis. Core needle biopsy showed diffuse infiltration by sheets of atypical cells with high nucleocytoplasmic ratio, inconspicuous nucleoli and scant cytoplasm (Fig. 1B). These cells were diffusely positive for leukocyte common antigen (LCA) and CD5 (T-cell marker); however, did not express CD20 (B-cell marker) (Fig. 1C). Hence, a diagnosis of primary T-cell lymphoma of thyroid (Non-Hodgkin’s type) was established. Contrast-enhanced computed tomography and bone marrow biopsy, performed as a part of staging, were normal.
Figs 1A to C: Case of primary T-cell non-Hodgkin’s lymphoma thyroid. (A) Hypercellular smears with atypical lymphoid cell population (Giemsa stain; 400×); (B) Core needle biopsy specimen displaying diffuse infiltration by atypical lymphoid cells (Hematoxylin and Eosin stain; 200×); (C) These atypical lymphoid cells show immunoreactivity for CD5
He was referred to the Department of Hematology for further evaluation and therapy. He underwent R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) based chemotherapy followed by external beam radiation therapy. He remained asymptomatic for 2 years and was lost to follow-up after that.
Case 2
A-50-year-old lady presented with a slightly growing, diffuse enlarged, thyroid gland for one and half years associated with cervical lymphadenopathy. Systemic and biochemical examinations were unremarkable. Fine needle aspiration (FNA) smears were hypercellular pictures with monomorphic plasmacytoid cells with binucleation at places, suggestive of Lymphoplasmacytic disorder. A core needle biopsy was advised for typing and immunohistochemical analysis, which revealed sheets of atypical plasmacytoid cells with interspersed areas infiltrated by lymphocytes. These plasmacytoid cells diffusely expressed CD 138 and displayed kappa monoclonality (Fig. 2). Serum protein electrophoresis was performed, which showed an elevated Gamma- M spike. Bone marrow examination showed normal hemopoiesis. Positron emission tomography-computed tomography (PET-CT) was done, which showed a heterogeneously enhancing, FDG avid ill-defined mass, measuring 10.4 × 9 × 7 cm with an SUV of 23.44, involving the entire thyroid gland with bilateral FDG avid cervical lymphadenopathy (SUV- 13.76). No other foci of lesions were identified, and a final diagnosis of solitary extramedullary plasmacytoma of the thyroid was made. She was treated with external beam radiotherapy with a complete response and is on regular follow-up.
Figs 2A to C: Extramedullary plasmacytoma thyroid. (A) FNA smears show predominantly plasma cells (mature and immature with few plasmablastic cells) (Giemsa stain, 400×); (B) Core biopsy displaying diffuse infiltration by plasma cells (H& E stain, 200×); (C) Diffuse membranous positivity for CD138
Case 3
A 49-year-old male presented with a gradually enlarging mass over the neck for two years associated with a change in his voice for 3 months. There was no history suggesting thyroid dysfunction or other compressive symptoms. On examination, a significant irregular swelling with a bosselated surface was present over the neck extending from the angle of the mandible to the suprasternal notch, which moved with deglutition. No lymph nodes were palpable, and bilateral carotids were pushed posterolaterally. Contrast-enhanced computerized tomography (CECT) revealed heterogeneous, massively enlarged thyroid lobes with irregular cystic changes. FNAC revealed multiple multinucleated giant cells with epithelioid cells, degenerated epithelial cells, and mixed inflammatory cells suggestive of granulomatous thyroiditis. A core needle biopsy was examined from representative site display histiocytic lesion with CD-68 and S-100 positivity and negative CD-1a. Due to discordance in clinical, radiological, and pathological findings, FNAC and core needle biopsy were repeated. IHC was positive for CD-1a, CD-68, and S-100 and negative for CK, PAX8, and CD21, and a final diagnosis of Langerhans cell histiocytosis (LCH) was made (Fig. 3).
Figs 3A and B: Langerhans cell histiocytosis thyroid. (A) Scattered population of atypical cells along with presence of multinucleated cells with foamy cytoplasm (Giemsa, 200×); (B) Hematoxylin and eosin stain (200×) displaying atypical cells with convoluted nuclear membrane and multinucleation with inflammatory cells in the background
Further systemic workup was performed to rule out systemic disease, which was unremarkable. The patient was started on cytarabine-based chemotherapy. The lesion responded well to the therapy, regressed significantly, and is now planned for thyroidectomy.
DISCUSSION
Differentiated cancers constitute the bulk of all thyroid malignancies. The unusual tumors’ incidence is very low and they lack a consensus on ideal management. Increased awareness and knowledge of available experiences are essential for diagnosing, managing, and improving outcomes of these lesions.
T-cell Lymphoma of Thyroid
Primary thyroid lymphoma (PTL) accounts for 1–2% of all thyroid malignancies and extranodal lymphomas.4 A marked female preponderance is seen (4:1). Most of the PTLs are non-Hodgkin’s lymphomas (NHLs) of B-cell origin, with ~20 cases of T-cell lymphoma thyroid reported so far.5 Like their B-cell counterparts, TCLs are also related to Hashimoto Thyroiditis, although causality has not been proved.6 It is also associated with human T-cell lymphotropic virus-related T-cell lymphomas/leukemia.6 Imaging studies are not very characteristic but a pseudocystic pattern on USG may be considered suspicious for lymphoma. Although lymphoma may be suspected on FNAC, they are often non-diagnostic and necessitate biopsy. Treatment options for B-cell NHL of thyroid are relatively well established, while regimens for TCL of thyroid have not yet fully evolved, and no survival statistics still exist for these cases, clearly owing to their rarity.
Owing to the rarity of the disease, the treatment protocol for TCL has not fully evolved yet, with the management options mostly following the established guidelines for B-cell lymphomas. Treatment depends upon the stage of the disease. Surgery is usually not preferred anymore. Radiation alone or chemotherapy (CHOP/R-CHOP) followed by radiation are preferred treatment modalities. Overall, TCLs are known to carry worse prognoses than B-cell lymphomas. However, it is observed that the TCL of the thyroid follows a rather indolent course.5
Extramedullary Plasmacytoma of Thyroid (EMP-T)
About 80–90% of EMP occur in the head and neck region, while EMP-T is extremely rare and accounts for about 1% of all EMP. Thyroid gland is one of the rarest sites of EMP, such that <50 cases have been reported so far.7–12 Lymphocytic thyroiditis and neck irradiation have been observed to predispose to EMP-T, although the association is not well established.13 Other authors have also reported the EMP of the thyroid in a background of lymphocytic thyroiditis.7 Cytomorphologically, it can mimic medullary carcinoma thyroid due to the plasmacytoid morphology of cells as well as the presence of amyloid in a few cases.13 While rendering a diagnosis of EMP of the thyroid, excluding the possibility of multiple myeloma is essential. A normal bone marrow examination confirms a diagnosis of EMP of the thyroid, absence of osteolytic lesions on a bone survey, lack of anemia/hypercalcemia/renal insufficiency that can be attributed to clonal proliferative disorder and normal levels of serum proteins on electrophoresis.7
The treatment of EMP remains controversial, and all three modalities, including radiotherapy alone, surgery alone, or a combined approach, are advocated by various authors.14 Chemotherapy is generally not recommended and can be considered for persistent disease after initial radiation.15 Patients with EMP have an excellent prognosis and carry a 10-year OS rate of 70%.16 7–10% of patients develop local recurrence after adequate RT, while 10–15% ultimately develop multiple myeloma.
Langerhans Cell Histiocytosis of Thyroid
Langerhans cell histiocytosis is a rare disorder of proliferation of dendritic Langerhans cells (LC).17 It is usually a systemic disease involving bones and extraskeletal involvement that occurs mainly in the skin, and pituitary, causing diabetes insipidus, liver/spleen and lungs.18 The incidence of LCH is 4–5.4 per million individuals, while only a handful of isolated LCH of the thyroid have been reported.19 Thyroid involvement is mostly seen in adults and has a slight female preponderance.20 Langerhans cell histiocytosis of the thyroid can present as a diffuse lesion or nodular enlargement and can often grow unevenly. The association of LCH of thyroid with central diabetes insipidus is well established. Association with lymphocytic thyroiditis, Graves’ disease, and papillary carcinoma have also been described.21 It has been hypothesized that these conditions have common pathogenesis pathways, and the underlying inflammatory process and BRAF mutations could also trigger PTC development.22 About 50– 65% of LCH are known to harbor BRAF mutations (mainly BRAFV600E), resulting in MAPK pathway activation at critical stages in myeloid differentiation.23 Management of LCH of the thyroid involves establishing the diagnosis and ruling out systemic involvement. FNAC may yield a confusing picture with features overlapping in many other conditions like lymphocytic and chronic granulomatous thyroiditis, cystic degeneration, tuberculosis, lymphoma, and anaplastic carcinoma.24
The cornerstone of diagnosis is identifying neoplastic LC, which are elongated to oval, with deeply grooved nuclei and abundant foamy cytoplasm.25 Normal LC are immunohistochemically positive for CD1a and/or Langerin and show the presence of Birbeck granules on electron microscopy. Demonstration of any of these forms the definitive diagnostic criteria of LCH.26
CONCLUSION
These three cases illustrate the diversity of uncommon thyroid pathologies, highlighting the need for a comprehensive approach to diagnosis and management. Primary T-cell lymphoma of the thyroid is exceedingly rare and requires tailored treatment strategies, although limited data are available due to its rarity. Extramedullary plasmacytoma of the thyroid is a rare entity often associated with thyroiditis and may mimic medullary carcinoma; management typically involves radiation therapy and, in some cases, surgery. Finally, while rare, LCH of the thyroid has been associated with various thyroid pathologies and is often treated with systemic approaches, including chemotherapy and BRAF inhibitors.
These cases underscore the importance of accurate diagnosis and the need for a multidisciplinary approach to effectively manage such unusual thyroid pathologies. Treatment modalities should be individualized, considering the patient’s clinical presentation and the extent of disease. Hence, thyroid pathology is a controversial area with high interobserver variability in the diagnosis of multiple types of thyroid tumors. Thyroid may be rarely involved with neoplasm common to another organ system. However, the histologic features of these rare tumors are quite unique, and the pathologist should be aware of these features to make the correct diagnosis. The prognosis depends on the tumor’s actual classification, making accurate diagnosis and classification critical for further management of the patients. Further research and comprehensive reporting of these rare cases are essential to enhance our understanding and refine treatment strategies for these unique thyroid pathologies.
ORCID
Chanchal Rana https://orcid.org/0000-0002-1783-7689
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