Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid
Hodgkin’s lymphoma (HL) is a malignant lymphoproliferative disease encompassing a wide spectrum of lymphoid neoplasms. It accounts for 8.2% of all lymphomas [
HL usually presents with painless lymphadenopathy (70%), mostly cervical in location (60–80%). B symptoms (fever, chills, and weight loss) are present in 20% of patients, may alert systemic involvement, and constitute a poor prognostic marker. Extranodal disease, as opposed to non-Hodgkin lymphomas (present in 33% of cases), is less frequent with HL (5–10%) [
Primary Malignant Lymphoma of the Thyroid is uncommon, accounting for less than 5% of all thyroid malignancies and up to 7% of all extranodal lymphomas [
The case of a patient bearing a nodular lymphocyte predominant Hodgkin’s lymphoma affecting the thyroid gland is reported.
The patient was a 76-year-old female followed up in the Thyroid Clinic for a thyroid nodule and primary hypothyroidism. The patient also had type 2 diabetes mellitus, arterial hypertension, and hypercholesterolemia. Regular medication included levothyroxine, ramipril, and simvastatin, diabetes being controlled with dietary measures only. Family and personal history were noncontributory and there was no previous radiation or iodine exposure. A thyroid nodule was first diagnosed upon clinical suspicion and ultrasound confirmation 2 years previous to her first Endocrinology Clinic visit. Imaging documented a large (29 × 44 × 31 mm transverse, longitudinal, and anteroposterior diameters, resp.), hypoechogenic, heterogeneous thyroid nodule of the left lobe with regular borders (Figure
(a) Thyroid nodule, large (29 × 44 × 31 mm transverse, longitudinal, and anteroposterior diameters, resp.) hypoechogenic heterogeneous thyroid nodule with regular borders; (b) lymph node, large (48 × 20 mm), hypoechoic, partly cystic lymph node.
3: FNA of the thyroid with follicular cells with suspicious nuclei (anisokaryosis, longitudinal grooves) on the background of a lymphocytic thyroiditis (Papanicolaou stain, 400x); 4: macroscopy features of the surgical specimens: left hemithyroidectomy (on top) and left cervical lymph node (on the bottom); 5: thyroid parenchyma with a diffuse infiltration of a lymphoid neoplasm (HE, 40x). These features were also found on the lymph node (not shown); 6: the neoplasm consisted of irregular nodules of follicular dendritic cells (CD21, 40x); 7: extensive background of CD4+ T-lymphocytes (CD4, 40x); 8: intermingled scattered large “popcorn cells” could be observed (HE, 200x); 9: the neoplastic popcorn cells were positive for CD20 (CD20, 200x); 10: they were negative for CD30 (CD30, 200x) and CD15 (not shown).
Laboratory studies were compatible with compensated primary hypothyroidism (TSH 2.32 IU/mL (normal range 0.4–4.68 IU/mL); free thyroxine 13 pmol/L (normal range 10–28 pmol/L)) along with marginally elevated thyroid autoantibody titer (antithyroid peroxidase, 71.8 IU/mL; negative antithyroglobulin results). No changes were seen on the complete blood count, lactate dehydrogenase, or erythrocyte sedimentation rate. No thyroid scintigraphy was done due to the absence of hyperthyroidism.
Fine needle aspirations (FNA) of the thyroid nodule were inconclusive; however, upon repetition, suspicion of papillary thyroid carcinoma (follicular and Hürthle cells with moderate degree anisokaryosis and nuclear grooves, Thy Class 4) on a thyroiditis background (mixed lymphoid population with predominance of small lymphocytes) arose. FNA of a suspicious lymph node was, on the other hand, suggestive of a lymphoproliferative disorder (monomorphic population of small lymphocytes and rare macrophages). Flow cytometry of both the thyroid nodule and a suspicious lymph node cytology specimen did not show any monoclonal lymphoid cells although there was a greatly increased CD4/CD8 ratio.
Upon suspicion of a differentiated thyroid cancer, total thyroidectomy with cervical lymph node dissection was performed. Intraoperative pathology consultation was requested for the thyroid specimen that showed a well delimitated, nonencapsulated, homogeneous, elastic, whitish nodule occupying the left thyroid lobe with 44 mm of greatest diameter. Frozen sections of the nodule revealed a nodular lymphoid proliferation suggestive of a malignant lymphoma. No evidence of papillary carcinoma was present. On paraffin sections the findings were similar to the those found on the lymph node. Regional cervical lymph node dissection revealed extensive HL involvement (16 out of 18 lymph nodes with evidence of HL). The lymph nodes had a macroscopically homogeneous whitish surface. Microscopy revealed architectural distortion induced by proliferation of multiple small nodules with irregular borders composed of dendritic cells (CD21+), numerous small CD4+ T lymphocytes, and few histiocytes and B lymphocytes. In this highly cellular background, a few large neoplastic cells with scant cytoplasm and large lobulated vacuolated nuclei with one or more red nucleoli (“popcorn cells”) were present. Very few mitotic figures could be seen and no necrosis could be appreciated. Immunohistochemistry of the neoplastic cells showed positivity for CD20 and negativity for CD30 and CD15 (Figure Diagnostic conclusion: both specimens were compatible with Nodular Lymphocyte Predominant Hodgkin’s Lymphoma (NLPHL).
Bone marrow biopsy and full body CT-scan revealed no further evidence of extranodal disease. Taken together, these results allowed classifying our patient’s HL in the stage IA.
Besides thyroidectomy and cervical lymphadenectomy, the patient subsequently underwent systemic chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). With treatment, a favorable neoplastic response was observed. A total of 5 cycles were completed. Unfortunately, because of significant cardiac toxicity from anthracyclines, hospital admission for acute congestive heart failure and significant performance status deterioration, chemotherapy was suspended (after 5 cycles). The patient is presently well and displays no evidence of disease recurrence, upon 30 months of follow-up.
Thyroid malignancies are increasingly being diagnosed in the current era of the “
Concerning Primary Thyroid Lymphomas, Hashimoto thyroiditis is considered a risk factor predisposing to its development and, in fact, in up to 40% of cases, concomitant primary hypothyroidism has been reported. Clinically, compressive symptoms are present in one-third and accompanying locoregional lymphadenopathy in 50% of cases. Regarding therapy, surgery may be indicated in some cases despite chemotherapy (with or without Radiation therapy) the being most frequently employed treatment modality [
Our literature search revealed thirty-nine cases of Hodgkin’s lymphoma located in the thyroid gland reported to date. Thyroid Hodgkin lymphoma affects mostly female patients (75–80% patients) with a median age of 42 years at the time of diagnosis [
Nodular lymphocyte predominant HL (NLPHL) constitutes a rare subtype of HL, accounting for no more than 10% of all cases of HL. It is considered a distinct clinical entity in that it differs from classical forms of HL in many aspects: Median age at presentation tends to be higher than in classical HL (30–40 years) and it has a greater male predominance (3 : 1). 70–80% of patients present with stage I-II disease and tend to have a higher propensity for peripheral lymph node involvement (neck and axilla). “B symptoms” are less frequent, being present in up to 10% of cases, which possibly reflects a lower systemic cytokine release (IL-2, -4, and -13). Extranodal involvement is rare, the spleen being the most commonly involved organ (10–15%). Bone marrow infiltration is found in less than 5% of cases.
Its hallmark histologic feature is the presence of malignant LP cells (histiocytic Reed-Sternberg cell variants) embedded within a nodular pattern of infiltrating lymphocytes. Malignant cells are described as “
Recommended management involves field or regional radiotherapy for patients with limited stage disease and combined modality therapy or chemotherapy for advanced stage disease. Response rates are very high, complete remission being achieved in 90–100% of patients. Relapses are unfortunately common within 3–6 years (10–35%); however, prognosis remains overall favorable (10-year survival rates of 80–90%) [
The patient described is, to our knowledge, the first documented case of nodular lymphocyte predominant HL involving the thyroid. Patient was older than was expected from what has been described with this HL subtype. Lymphocytic thyroiditis was definitely present which may have been a decisive risk factor and a possible factor underlying difficulty in establishing the definite diagnosis. Primary Malignant Lymphoma of the thyroid diagnosis was assumed postoperatively justifying the adjuvant postoperative conventional chemotherapy for HL (ABVD regimen). Lymphoma free survival is reported after 2 years of follow-up despite possible significant treatment toxicity (heart failure).
Thyroid nodules are frequent clinical and radiological findings, the majority being benign in nature. Among thyroid malignancies, lymphomas are quite rare and are usually of non-Hodgkin’s subtype. Hodgkin lymphomas of the thyroid are even more unusual, only 40 cases being described so far (mostly of the nodular sclerosis subtype). Nodular lymphocyte predominant HL is considered to represent a distinct form of HL regarding epidemiological distribution, biological behavior, histological hallmarks, and prognosis. The authors report on the first described case of a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid.
The authors declare that there is no conflict of interests regarding the publication of this paper.