CASE REPORT
Jonathan Irish, MD, FRCSC, Section Editor
Primary thyroid diffuse large B-cell lymphoma coexistent with papillary thyroid carcinoma: A case report Shumin Xie, MD,1 Wei Liu, MD,1 Yuyan Xiang, MS,2 Yinghuan Dai, MD,3 Jihao Ren, MD,1* 1
Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China, 2Department of Human Anatomy, University of South China, Hengyang, People’s Republic of China, 3Department of Pathology, The Second Xiangya Hospital of Central South University, People’s Republic of China.
Accepted 24 October 2014 Published online 26 May 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23917
ABSTRACT: Background. Primary thyroid lymphoma (PTL) is uncommon, accounting for 2% to 5% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer. The coexistence of PTL and PTC is very rare, and the preoperative diagnosis is rather difficult. Methods. A 41-year-old male patient complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month was presented. Imaging demonstrated an enlarged thyroid and a mass in the thyroid. Results. Surgery was conducted, and the final diagnosis of coexistence of PTL and PTC was confirmed by histopathological and immunohisto-
INTRODUCTION Primary thyroid lymphoma (PTL) is very uncommon, accounting for 2% to 5% of all thyroid malignancies, with a distinct elderly female predominance and incidence peak between 60 and 69 years old.1,2 A vast majority of PTL arise in the setting of Hashimoto thyroiditis.3–5 Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer and constitutes nearly 80% of all thyroid cancers, occurring predominately in women in the third to fourth decade of life.6 The coexistence of both is very rare, and the preoperative diagnosis is rather difficult. In this case report, we described a rare condition in which the diffuse large B-cell lymphoma of the thyroid coexistents with PTC in a middle-aged male patient.
CASE REPORT A 41-year-old male patient was referred to the Otolaryngology Head and Neck Surgery Clinic of the Second Xiangya Hospital, complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month, without hoarseness, dysphagia, or dyspnea. Local physical examina-
chemical examination. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. After 2 months of follow-up, no recurrence or metastasis was noted. Conclusion. This rare case highlights the importance for physicians to keep PTL in mind for differential diagnosis in patients with sudden thyroid enlargement and who have clinical history of Hashimoto thyroiditis. C 2015 Wiley Periodicals, Inc. Head Neck 37: E109–E114, 2015 V
KEY WORDS: primary thyroid lymphoma, papillary thyroid carcinoma, coexistence, diffuse large B-cell lymphoma, therapy
tion disclosed an enlarged left lobe of the thyroid with a hard, nontender mass in the left lobe of the thyroid. There were no clinically palpable cervical lymph nodes. The family history and medical history were noncontributory. During the hospital stay, relevant examinations were performed on this patient. An electrocardiogram was unremarkable. Complete blood count, coagulant function, serum electrolytes serology, and chest X-ray were normal. Thyroid function test showed normal functioning of the thyroid except for the high level of thyroid peroxidase antibody (anti-TPO). On cervical ultrasound, the right lobe of the thyroid was in a normal shape, while the isthmus and left lobe of the thyroid were enlarged with heterogeneous hypoechoic nodularity and diffused hyperechoic areas, which measures 7.7 3 3.6 3 2.9 cm for the left lobe. Blood flow imaging was also observed in the heterogeneous hypoechoic nodularity. Meanwhile, a plain CT scan displayed an enlarged thyroid and an irregular shaped mass in low-density with a poorly defined boundary in the left lobe of the thyroid, measuring 3.0 3 1.7 cm (Figure 1A). On the enhanced CT scan, the mass was heterogeneously enhanced, and possessed a lower density than the normal thyroid tissues. Bone destruction and enlarged cervical lymph nodes were not observed (Figure 1B).
Shumin Xie and Wei Liu contributed equally to this work. *Corresponding author: J. Ren, Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, People’s Republic of China, 410000. E-mail: [email protected]
RESULTS The patient was scheduled for resection of the isthmus and left lobe of the thyroid, removing the mass, and HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
E109
XIE ET AL.
FIGURE 1. (A) The plain CT scan displayed an enlarged thyroid and an irregular shaped mass in low-density with a poorly defined boundary in the left lobe of thyroid. (B) The enhanced CT scan showed that the mass was heterogeneously enhanced, and possessed a lower density than the normal thyroid tissues.
dissection of the left cervical lymph nodes. The recurrent laryngeal nerve and parathyroids were preserved. The mass was hard with an unsmooth surface, and measured 4.0 3 3.0 3 2.5 cm. Additionally, multiple hard and fixed lymph nodes were palpable in the left side of the neck. The histopathology examination showed diffuse
proliferative small round cells with obvious atypia in the thyroid, left tracheoesophageal groove lymph nodes, and strap muscle. Meanwhile, a tiny focus of papillary carcinoma was also discovered (Figure 2). Immunohistochemistry showed these cells to be immunoreactive for CD10, CD20, Ki-67, PAX-5, CD45RO, and Bcl-6, which
FIGURE 2. (A) Hematoxylin-eosin staining showed the coexistence of primary thyroid lymphoma (PTL) and papillary thyroid carcinoma (PTC; original magnification 340). (B) Hematoxylin-eosin staining showed the coexistence of PTL and PTC (original magnification 3100). (C) Hematoxylineosin staining showed the lesion of PTL (original magnification 3100). (D) Hematoxylin-eosin staining showed the lesion of PTC (original magnification 3100).
E110
HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
COEXISTENCE
OF PRIMARY THYROID LYMPHOMA AND
PTC
FIGURE 3. Immunohistochemistry assay displayed the CD10, CD 20, Ki-67, PAX-5, CD45RO, and Bcl-6 positivity in primary thyroid lymphoma (PTL) lesions.
suggested large B-cell lymphoma (Figure 3). Therefore, the final diagnosis of primary thyroid diffuse large B-cell lymphoma coexistent with PTC was made. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. The patient tolerated the treatment well and after 2 months of follow-up, no recurrence or metastasis was noted.
DISCUSSION PTL is very rare, accounting for 2% to 5% of all thyroid malignancies, and consists of 3 subtypes, including diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, as well as follicular lymphoma. The non-Hodgkin’s lymphoma of B-cell type is the most common subtype. It occurs most frequently in the elderly woman linked with chronic autoimmune thyroiditis, being moderate to poor in degree of differentiation. However, our case was a 41-year-old male patient, and PTL occurring in middle-aged patients is rather rare. Constituting nearly 80% of all thyroid cancer, PTC is the most common type of thyroid malignancy with the lowest level of malignancy. To our knowledge, the coexistence of PTL and PTC is very rare, and only several cases have been previously reported4,7–10 (Table 1). The etiopathogenesis of PTL is still unknown, and may be correlated with virus infection and immune deficiency.11 According to literature, nearly 40% to 85% of
PTL occur in a previous autoimmune thyroid disease,3,4 probably as a result from the B-cells that are activated by chronic lymphocytic thyroiditis or Hashimoto thyroiditis, and secrete auto-antibody, leading to the proliferation of thyroid lymphoid tissues and malignant transformation.11 The estimated risk of developing a thyroid lymphoma is increased to 67 to 80-fold in patients with Hashimoto thyroiditis and evolution to PTL occurs in 0.5% of patients.7 Meanwhile, papillary carcinoma is one of the complications of Hashimoto thyroiditis.4 Several retrospective studies have revealed a strong correlation between these 2 diseases, whereas some studies have failed to show any such association.4,7,8 In our case report, the level of antiTPO was obviously high, however, the patient did not have a definite history of Hashimoto thyroiditis. Currently, the preoperative diagnosis of PTL is meeting a great deal of challenges.12 On ultrasound and CT scan, no specific appearance will be found, and just presents as a diffusely enlarged thyroid accompanied with nodular tissue, which is similar to Hashimoto thyroiditis. The fine-needle aspiration (FNA) cytology is considered to be limited in preoperative diagnosis by some researchers,4,8,10 whereas others think that it has a sensitivity of >90% and negative predictive value of 96% in detecting these lesions.7 As a result, the preoperative diagnosis of simultaneous occurrence of PTL and PTC is difficult. The patient in this case report had not been correctly diagnosed before surgery. These days, the postoperative histopathology and immunohistochemistry are recognized as HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
E111
E112
HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
Male/61
Female/32
Male/59
Melo et al8
Jayaprakash et al4
Cheng et al7
A sudden size increase of thyroid nodule for 15 d Thyroid nodules with known hypothyroidism from HT
A multinodular goiter revealed by ultrasound without symptoms Fast painless thyroid enlargement
Thyroid nodular palpitations without other symptoms
A rapidly growing lump on neck, aphasia, and shortness of breath
Presentation
A multinodular goiter with some nodules presenting gross calcification Enlarged thyroid with nodularity and hyperechoic areas A heterogeneous thyroid with 2 hypoechoic nodules
A multinodular goiter
A multinodular goiter
A 6 3 3 cm nodule in the right lobe
Thyroid ultrasound
Unreported
High TSH and decreased T4 levels
TSH and FT4 were elevated. Anti-TPO, anti-Tg were positive TSH and FT4 were normal. Anti-TPO and anti-Tg were positive Anti-Tg was positive
Normal
Thyroid function test
The FNA revealed PTC and atypical lymphoid cells in a background of HT
The FNA showed the coexistence of HT and PTC
Unreported
The FNA was suspicious for malignancy
The FNA diagnosed the coexistence of PTC and HT
The FNA result was consistent with PTL
Preoperative diagnosis
Marginal zone B-cell lymphoma of MALT type in the right lobe and PTC in the left lobe
HT coexisting with PTC and primary PTL (B-cell lineage)
Thyroid diffuse large B-cell lymphoma in the right lobe, and papillary microcarcinoma in the left lobe PTC in the right lobe, MALT lymphoma in the left lobe, and extensive HT in the whole thyroid PTC in the left lobe, follicular carcinoma in the right lobe, and PTL infiltrating the thyroid parenchyma Multicentric PTC accompanied of HT and thyroid MALT lymphoma in a nodule
Pathologic diagnosis
Total thyroidectomy, levothyroxine therapy and CHOP chemotherapy Total thyroidectomy and 131I radiotherapy
Total thyroidectomy and levothyroxine therapy
Total thyroidectomy, thyroxine treatment and 131I radiotherapy
Total thyroidectomy, thyroxine treatment and 131I radiotherapy
Total thyroidectomy and levothyroxine therapy
Therapy
No recurrence for 7 y
No recurrence for 1 y
No recurrence for 2 y
Asymptomatic for 12 mo
Asymptomatic for 14 mo
No recurrence for 2 y
Follow-up
Abbreviations: FNA, fine-needle aspiration; PTL, primary thyroid lymphoma; TSH, thyroid-stimulating hormone; FT4, free thyroxine; TPO, thyroperoxidase antibody; Tg, thyroglobulin; PTC, papillary thyroid carcinoma; HT, Hashimoto thyroiditis; MALT, mucosaassociated lymphoid tissue; CHOP, cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone.
Male/63
Vassilatou et al10
Female/50
Female/51
9
Sex/age, y
Vassilatou et al10
Cakir et al
Series
TABLE 1. The previously reported cases of the coexistence of primary thyroid lymphoma and papillary thyroid carcinoma.
XIE ET AL.
COEXISTENCE
the golden standard for PTL diagnosis. From the extensive list of markers, the ones that have shown acceptable sensitivity and specificity include low and high molecular weight cytokeratin, galectin 3, HBME-1, and cyclooxygenase 2.13,14 In our case, the resected tissue was submitted to routine histopathological evaluation and immunohistochemistry analysis with a panel of monoclonal antibodies, discovering positive expression of CD10, CD 20, Ki-67, PAX-5, CD45RO, and bcl-6, which confirmed the final diagnosis. Differential diagnosis between PTL and generalized lymphoma with thyroid involvement must be performed. Clinically, PTL has the presentation of painless rapid mass growth in the thyroid, sometimes with compressive symptoms.15 However, symptoms like fever, weight loss more than 10%, and nocturnal sweating suggest typical disseminated lymphoma either primary in the thyroid gland or in other sites. Preoperative examinations, such as ultrasound and CT scan, can be indistinguishable for compressive goiter. In this report, as in a few other cases, the PTL was confirmed only after surgery. Moreover, differential diagnosis of Hashimoto thyroiditis, medullary thyroid carcinoma, and anaplastic carcinoma should also be taken into consideration. The Ann Arbor Classification for Lymphomas, modified by Sakorafas was as follows16: stage IE disease corresponds to disease confined to the thyroid; stage IIE refers to disease confined to the thyroid gland and the regional lymph nodes on the same side of the diaphragm; stage IIIE corresponds to disease confined to the thyroid and lymph nodes on both sides of the diaphragm and/or spleen; and stage IVE refers to disease in nodal and/or additional extranodal involvement. Localized disease was defined as stage IE and stage IIE disease, and disseminated disease as stage IIIE and stage IVE. The present case was stage as IVE (disseminated disease). There has been no literature to date regarding the optimal management of the simultaneous occurrence of PTL and PTC. The management of one is not affected by the management of the other, and the prognosis is probably affected by the one having the worst stage.14 For PTC, surgical resection is the common treatment; although the therapeutic strategy is chosen mainly based on the subtype and stage of PTL. Currently, the surgery is not the conventional therapy for PTL, and it is only adopted to relief the compression of trachea and esophagus, and to obtain specimens for final diagnosis.9,16,17 It is notable that for patients who are diagnosed with the coexistence of PTL and PTC, total thyroid resection is not necessary, but the PTC-affected lobe of the thyroid is suggested to be resected as complete as possible because the main treatment of PTC is surgical resection. Additionally, radiotherapy, chemotherapy, and the combination of surgery and radiochemotherapy are often adopted for PTL treatment. The radiotherapy should be given in medium doses ranging from 40 to 50 Gy in the field of the whole neck, bilateral supraclavicular and infraclavicular region, and superior mediastinum. Besides, the CHOP chemotherapy is widely adopted for disseminated or locally aggressive PTL, and many patients can benefit from it. Usually, CHOP chemotherapy followed by involved-field radiotherapy is superior to CHOP alone for the treatment of
OF PRIMARY THYROID LYMPHOMA AND
PTC
localized intermediate-grade and high-grade non-Hodgkin’s lymphoma.18 For diffuse large B-cell lymphoma, the combination of surgery, chemotherapy, and radiotherapy is the best choice,18 which is the therapeutic strategy for the patient in this report. Although for early stage MALT lymphoma, surgery or radiotherapy alone can achieve a satisfactory therapeutic effect.19 Prognosis of PTL depends on the spread of the disease and the grade of the tumor. In early diagnosed cases, 5year survival rate is about 80% if the tumor is limited to the thyroid, whereas the rate decreases to 35% if there is a lymphatic spread in the neck, and if a widespread retention exists, the rate even goes down to 5%.9 A previous study demonstrated that the presence of mediastinal lymph node involvement was the most important prognostic factor for PTL.20 As for PTC, the prognosis of occult papillary cancer with a diameter
Jonathan Irish, MD, FRCSC, Section Editor
Primary thyroid diffuse large B-cell lymphoma coexistent with papillary thyroid carcinoma: A case report Shumin Xie, MD,1 Wei Liu, MD,1 Yuyan Xiang, MS,2 Yinghuan Dai, MD,3 Jihao Ren, MD,1* 1
Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China, 2Department of Human Anatomy, University of South China, Hengyang, People’s Republic of China, 3Department of Pathology, The Second Xiangya Hospital of Central South University, People’s Republic of China.
Accepted 24 October 2014 Published online 26 May 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23917
ABSTRACT: Background. Primary thyroid lymphoma (PTL) is uncommon, accounting for 2% to 5% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer. The coexistence of PTL and PTC is very rare, and the preoperative diagnosis is rather difficult. Methods. A 41-year-old male patient complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month was presented. Imaging demonstrated an enlarged thyroid and a mass in the thyroid. Results. Surgery was conducted, and the final diagnosis of coexistence of PTL and PTC was confirmed by histopathological and immunohisto-
INTRODUCTION Primary thyroid lymphoma (PTL) is very uncommon, accounting for 2% to 5% of all thyroid malignancies, with a distinct elderly female predominance and incidence peak between 60 and 69 years old.1,2 A vast majority of PTL arise in the setting of Hashimoto thyroiditis.3–5 Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer and constitutes nearly 80% of all thyroid cancers, occurring predominately in women in the third to fourth decade of life.6 The coexistence of both is very rare, and the preoperative diagnosis is rather difficult. In this case report, we described a rare condition in which the diffuse large B-cell lymphoma of the thyroid coexistents with PTC in a middle-aged male patient.
CASE REPORT A 41-year-old male patient was referred to the Otolaryngology Head and Neck Surgery Clinic of the Second Xiangya Hospital, complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month, without hoarseness, dysphagia, or dyspnea. Local physical examina-
chemical examination. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. After 2 months of follow-up, no recurrence or metastasis was noted. Conclusion. This rare case highlights the importance for physicians to keep PTL in mind for differential diagnosis in patients with sudden thyroid enlargement and who have clinical history of Hashimoto thyroiditis. C 2015 Wiley Periodicals, Inc. Head Neck 37: E109–E114, 2015 V
KEY WORDS: primary thyroid lymphoma, papillary thyroid carcinoma, coexistence, diffuse large B-cell lymphoma, therapy
tion disclosed an enlarged left lobe of the thyroid with a hard, nontender mass in the left lobe of the thyroid. There were no clinically palpable cervical lymph nodes. The family history and medical history were noncontributory. During the hospital stay, relevant examinations were performed on this patient. An electrocardiogram was unremarkable. Complete blood count, coagulant function, serum electrolytes serology, and chest X-ray were normal. Thyroid function test showed normal functioning of the thyroid except for the high level of thyroid peroxidase antibody (anti-TPO). On cervical ultrasound, the right lobe of the thyroid was in a normal shape, while the isthmus and left lobe of the thyroid were enlarged with heterogeneous hypoechoic nodularity and diffused hyperechoic areas, which measures 7.7 3 3.6 3 2.9 cm for the left lobe. Blood flow imaging was also observed in the heterogeneous hypoechoic nodularity. Meanwhile, a plain CT scan displayed an enlarged thyroid and an irregular shaped mass in low-density with a poorly defined boundary in the left lobe of the thyroid, measuring 3.0 3 1.7 cm (Figure 1A). On the enhanced CT scan, the mass was heterogeneously enhanced, and possessed a lower density than the normal thyroid tissues. Bone destruction and enlarged cervical lymph nodes were not observed (Figure 1B).
Shumin Xie and Wei Liu contributed equally to this work. *Corresponding author: J. Ren, Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, People’s Republic of China, 410000. E-mail: [email protected]
RESULTS The patient was scheduled for resection of the isthmus and left lobe of the thyroid, removing the mass, and HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
E109
XIE ET AL.
FIGURE 1. (A) The plain CT scan displayed an enlarged thyroid and an irregular shaped mass in low-density with a poorly defined boundary in the left lobe of thyroid. (B) The enhanced CT scan showed that the mass was heterogeneously enhanced, and possessed a lower density than the normal thyroid tissues.
dissection of the left cervical lymph nodes. The recurrent laryngeal nerve and parathyroids were preserved. The mass was hard with an unsmooth surface, and measured 4.0 3 3.0 3 2.5 cm. Additionally, multiple hard and fixed lymph nodes were palpable in the left side of the neck. The histopathology examination showed diffuse
proliferative small round cells with obvious atypia in the thyroid, left tracheoesophageal groove lymph nodes, and strap muscle. Meanwhile, a tiny focus of papillary carcinoma was also discovered (Figure 2). Immunohistochemistry showed these cells to be immunoreactive for CD10, CD20, Ki-67, PAX-5, CD45RO, and Bcl-6, which
FIGURE 2. (A) Hematoxylin-eosin staining showed the coexistence of primary thyroid lymphoma (PTL) and papillary thyroid carcinoma (PTC; original magnification 340). (B) Hematoxylin-eosin staining showed the coexistence of PTL and PTC (original magnification 3100). (C) Hematoxylineosin staining showed the lesion of PTL (original magnification 3100). (D) Hematoxylin-eosin staining showed the lesion of PTC (original magnification 3100).
E110
HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
COEXISTENCE
OF PRIMARY THYROID LYMPHOMA AND
PTC
FIGURE 3. Immunohistochemistry assay displayed the CD10, CD 20, Ki-67, PAX-5, CD45RO, and Bcl-6 positivity in primary thyroid lymphoma (PTL) lesions.
suggested large B-cell lymphoma (Figure 3). Therefore, the final diagnosis of primary thyroid diffuse large B-cell lymphoma coexistent with PTC was made. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. The patient tolerated the treatment well and after 2 months of follow-up, no recurrence or metastasis was noted.
DISCUSSION PTL is very rare, accounting for 2% to 5% of all thyroid malignancies, and consists of 3 subtypes, including diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, as well as follicular lymphoma. The non-Hodgkin’s lymphoma of B-cell type is the most common subtype. It occurs most frequently in the elderly woman linked with chronic autoimmune thyroiditis, being moderate to poor in degree of differentiation. However, our case was a 41-year-old male patient, and PTL occurring in middle-aged patients is rather rare. Constituting nearly 80% of all thyroid cancer, PTC is the most common type of thyroid malignancy with the lowest level of malignancy. To our knowledge, the coexistence of PTL and PTC is very rare, and only several cases have been previously reported4,7–10 (Table 1). The etiopathogenesis of PTL is still unknown, and may be correlated with virus infection and immune deficiency.11 According to literature, nearly 40% to 85% of
PTL occur in a previous autoimmune thyroid disease,3,4 probably as a result from the B-cells that are activated by chronic lymphocytic thyroiditis or Hashimoto thyroiditis, and secrete auto-antibody, leading to the proliferation of thyroid lymphoid tissues and malignant transformation.11 The estimated risk of developing a thyroid lymphoma is increased to 67 to 80-fold in patients with Hashimoto thyroiditis and evolution to PTL occurs in 0.5% of patients.7 Meanwhile, papillary carcinoma is one of the complications of Hashimoto thyroiditis.4 Several retrospective studies have revealed a strong correlation between these 2 diseases, whereas some studies have failed to show any such association.4,7,8 In our case report, the level of antiTPO was obviously high, however, the patient did not have a definite history of Hashimoto thyroiditis. Currently, the preoperative diagnosis of PTL is meeting a great deal of challenges.12 On ultrasound and CT scan, no specific appearance will be found, and just presents as a diffusely enlarged thyroid accompanied with nodular tissue, which is similar to Hashimoto thyroiditis. The fine-needle aspiration (FNA) cytology is considered to be limited in preoperative diagnosis by some researchers,4,8,10 whereas others think that it has a sensitivity of >90% and negative predictive value of 96% in detecting these lesions.7 As a result, the preoperative diagnosis of simultaneous occurrence of PTL and PTC is difficult. The patient in this case report had not been correctly diagnosed before surgery. These days, the postoperative histopathology and immunohistochemistry are recognized as HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
E111
E112
HEAD & NECK—DOI 10.1002/HED
SEPTEMBER 2015
Male/61
Female/32
Male/59
Melo et al8
Jayaprakash et al4
Cheng et al7
A sudden size increase of thyroid nodule for 15 d Thyroid nodules with known hypothyroidism from HT
A multinodular goiter revealed by ultrasound without symptoms Fast painless thyroid enlargement
Thyroid nodular palpitations without other symptoms
A rapidly growing lump on neck, aphasia, and shortness of breath
Presentation
A multinodular goiter with some nodules presenting gross calcification Enlarged thyroid with nodularity and hyperechoic areas A heterogeneous thyroid with 2 hypoechoic nodules
A multinodular goiter
A multinodular goiter
A 6 3 3 cm nodule in the right lobe
Thyroid ultrasound
Unreported
High TSH and decreased T4 levels
TSH and FT4 were elevated. Anti-TPO, anti-Tg were positive TSH and FT4 were normal. Anti-TPO and anti-Tg were positive Anti-Tg was positive
Normal
Thyroid function test
The FNA revealed PTC and atypical lymphoid cells in a background of HT
The FNA showed the coexistence of HT and PTC
Unreported
The FNA was suspicious for malignancy
The FNA diagnosed the coexistence of PTC and HT
The FNA result was consistent with PTL
Preoperative diagnosis
Marginal zone B-cell lymphoma of MALT type in the right lobe and PTC in the left lobe
HT coexisting with PTC and primary PTL (B-cell lineage)
Thyroid diffuse large B-cell lymphoma in the right lobe, and papillary microcarcinoma in the left lobe PTC in the right lobe, MALT lymphoma in the left lobe, and extensive HT in the whole thyroid PTC in the left lobe, follicular carcinoma in the right lobe, and PTL infiltrating the thyroid parenchyma Multicentric PTC accompanied of HT and thyroid MALT lymphoma in a nodule
Pathologic diagnosis
Total thyroidectomy, levothyroxine therapy and CHOP chemotherapy Total thyroidectomy and 131I radiotherapy
Total thyroidectomy and levothyroxine therapy
Total thyroidectomy, thyroxine treatment and 131I radiotherapy
Total thyroidectomy, thyroxine treatment and 131I radiotherapy
Total thyroidectomy and levothyroxine therapy
Therapy
No recurrence for 7 y
No recurrence for 1 y
No recurrence for 2 y
Asymptomatic for 12 mo
Asymptomatic for 14 mo
No recurrence for 2 y
Follow-up
Abbreviations: FNA, fine-needle aspiration; PTL, primary thyroid lymphoma; TSH, thyroid-stimulating hormone; FT4, free thyroxine; TPO, thyroperoxidase antibody; Tg, thyroglobulin; PTC, papillary thyroid carcinoma; HT, Hashimoto thyroiditis; MALT, mucosaassociated lymphoid tissue; CHOP, cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone.
Male/63
Vassilatou et al10
Female/50
Female/51
9
Sex/age, y
Vassilatou et al10
Cakir et al
Series
TABLE 1. The previously reported cases of the coexistence of primary thyroid lymphoma and papillary thyroid carcinoma.
XIE ET AL.
COEXISTENCE
the golden standard for PTL diagnosis. From the extensive list of markers, the ones that have shown acceptable sensitivity and specificity include low and high molecular weight cytokeratin, galectin 3, HBME-1, and cyclooxygenase 2.13,14 In our case, the resected tissue was submitted to routine histopathological evaluation and immunohistochemistry analysis with a panel of monoclonal antibodies, discovering positive expression of CD10, CD 20, Ki-67, PAX-5, CD45RO, and bcl-6, which confirmed the final diagnosis. Differential diagnosis between PTL and generalized lymphoma with thyroid involvement must be performed. Clinically, PTL has the presentation of painless rapid mass growth in the thyroid, sometimes with compressive symptoms.15 However, symptoms like fever, weight loss more than 10%, and nocturnal sweating suggest typical disseminated lymphoma either primary in the thyroid gland or in other sites. Preoperative examinations, such as ultrasound and CT scan, can be indistinguishable for compressive goiter. In this report, as in a few other cases, the PTL was confirmed only after surgery. Moreover, differential diagnosis of Hashimoto thyroiditis, medullary thyroid carcinoma, and anaplastic carcinoma should also be taken into consideration. The Ann Arbor Classification for Lymphomas, modified by Sakorafas was as follows16: stage IE disease corresponds to disease confined to the thyroid; stage IIE refers to disease confined to the thyroid gland and the regional lymph nodes on the same side of the diaphragm; stage IIIE corresponds to disease confined to the thyroid and lymph nodes on both sides of the diaphragm and/or spleen; and stage IVE refers to disease in nodal and/or additional extranodal involvement. Localized disease was defined as stage IE and stage IIE disease, and disseminated disease as stage IIIE and stage IVE. The present case was stage as IVE (disseminated disease). There has been no literature to date regarding the optimal management of the simultaneous occurrence of PTL and PTC. The management of one is not affected by the management of the other, and the prognosis is probably affected by the one having the worst stage.14 For PTC, surgical resection is the common treatment; although the therapeutic strategy is chosen mainly based on the subtype and stage of PTL. Currently, the surgery is not the conventional therapy for PTL, and it is only adopted to relief the compression of trachea and esophagus, and to obtain specimens for final diagnosis.9,16,17 It is notable that for patients who are diagnosed with the coexistence of PTL and PTC, total thyroid resection is not necessary, but the PTC-affected lobe of the thyroid is suggested to be resected as complete as possible because the main treatment of PTC is surgical resection. Additionally, radiotherapy, chemotherapy, and the combination of surgery and radiochemotherapy are often adopted for PTL treatment. The radiotherapy should be given in medium doses ranging from 40 to 50 Gy in the field of the whole neck, bilateral supraclavicular and infraclavicular region, and superior mediastinum. Besides, the CHOP chemotherapy is widely adopted for disseminated or locally aggressive PTL, and many patients can benefit from it. Usually, CHOP chemotherapy followed by involved-field radiotherapy is superior to CHOP alone for the treatment of
OF PRIMARY THYROID LYMPHOMA AND
PTC
localized intermediate-grade and high-grade non-Hodgkin’s lymphoma.18 For diffuse large B-cell lymphoma, the combination of surgery, chemotherapy, and radiotherapy is the best choice,18 which is the therapeutic strategy for the patient in this report. Although for early stage MALT lymphoma, surgery or radiotherapy alone can achieve a satisfactory therapeutic effect.19 Prognosis of PTL depends on the spread of the disease and the grade of the tumor. In early diagnosed cases, 5year survival rate is about 80% if the tumor is limited to the thyroid, whereas the rate decreases to 35% if there is a lymphatic spread in the neck, and if a widespread retention exists, the rate even goes down to 5%.9 A previous study demonstrated that the presence of mediastinal lymph node involvement was the most important prognostic factor for PTL.20 As for PTC, the prognosis of occult papillary cancer with a diameter
