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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune thyroiditis is associated with the development of thyroid lymphoma&#44; and in particular mucosa-associated lymphoid tissue &#40;MALT&#41; lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> though this type occurs in only 0&#46;5&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It has been reported that 20&#8211;30 years are needed for a lymphoma to develop as a result of autoimmune thyroiditis&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The association between thyroiditis and Hodgkin&#39;s lymphoma &#40;HL&#41; is more questionable&#44; and is difficult to clarify due to the low number of cases of HL that arise&#46; Nevertheless&#44; in a previous study of 21 HL patients&#44; 7 presented autoimmune thyroiditis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The hypothesis of an association between the two conditions is based on the fact that the thyroid gland does not contain native lymphoid tissue&#59; therefore&#44; intrathyroid lymphoid tissue develops because of the presence of autoimmune thyroiditis&#46; In this context&#44; antigenic stimulation of lymphocytes in autoimmune disorders may trigger a malignant transformation&#46; Primary extranodal HL accounts for less than 2&#37; of extranodal lymphomas<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and usually occurs due to the spreading of a contiguous lymphatic ganglion or hematogenous dissemination&#46; It is questionable whether this is actually a primary disease&#44; as it usually has an extrathyroid origin&#46; Moreover it is considerably infrequent&#44; with only 37 cases reported until now in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Its diagnosis is confirmed by the presence of Reed&#8211;Sternberg cells&#46; We report the case of a patient with autoimmune thyroiditis with a fast-growing thyroid nodule&#46; No evidence was detected of another tumor foci or adjacent lymphadenopathy&#44; which led us to consider a diagnosis of primary thyroid gland HL&#46; The peculiarity of this case lies in that&#44; despite suffering autoimmune thyroiditis&#44; the patient developed HL rather than MALT lymphoma&#44; which is the usual clinical course in such cases&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Patient</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 54-year-old woman was monitored for subclinical autoimmune hypothyroidism with anti-peroxidase antibodies 2933&#46;70<span class="elsevierStyleHsp" style=""></span>U per mililiter&#46; At the time&#44; she was receiving treatment with 75<span class="elsevierStyleHsp" style=""></span>&#956;g per day of levothyroxine&#46; Her thyroid function was controlled with TSH 1&#46;90<span class="elsevierStyleHsp" style=""></span>&#956;IU per mililiter and T4 free 1&#46;3<span class="elsevierStyleHsp" style=""></span>ng per deciliter&#46; The patient had no family history of thyroid pathology and no personal history of toxic substance abuse&#46; During her initial visit&#44; her cervical palpation was found to be normal&#44; and a thyroid ultrasound scan revealed a solid left thyroid nodule with a maximum diameter of 9<span class="elsevierStyleHsp" style=""></span>mm that was hypoechoic&#44; clearly defined&#44; avascular and without calcification&#46; According to current guidelines of clinical practice&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> fine needle-aspiration biopsy &#40;FNAB&#41; was not indicated&#46; Ultrasound was scheduled one year later and revealed no significant changes&#46; Three years later&#44; the thyroid lesion began growing rapidly&#44; demonstrating a palpable thyroid nodule with a maximum diameter of 2<span class="elsevierStyleHsp" style=""></span>cm&#46; Ultrasound revealed an increase in the size of the nodule to 17&#46;8<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>22&#46;6<span class="elsevierStyleHsp" style=""></span>mm&#44; and showed it to be solid&#44; occupying practically all the left thyroid lobe&#44; hypoechoic&#44; unstructured and heterogeneous&#44; with mixed vascularization and without microcalcifications &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In response to these developments&#44; FNAB was carried out and revealed atypically large and multinucleate lymphocytes with features of Reed&#8211;Sternberg cells&#44; which raised suspicions of lymphoma &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Given the difficulty in distinguishing between inflammatory and lymphoproliferative processes &#40;especially MALT-type LNH&#41; in a patient with autoimmune thyroiditis&#44; it was decided to repeat FNAB with flow cytometry&#46; Atypical lymphocytes were observed once again&#44; but there was no sign of infiltration due to lymphoma &#40;CD3<span class="elsevierStyleSup">&#43;</span> T lymphocytes were observed in 48&#37;&#44; of which 73&#37; were CD4<span class="elsevierStyleSup">&#43;</span> and 22&#37; were CD8<span class="elsevierStyleSup">&#43;</span>&#59; 44&#37; were polyclonal CD19<span class="elsevierStyleSup">&#43;</span> B lymphocytes without evidence of immature cells&#41;&#46; In light of these results&#44; a biopsy was carried out &#40;left hemithyroidectomy&#41; to confirm a suspected thyroid HL&#46; The intraoperative biopsy suggested autoimmune thyroiditis without any evidence of lymphoma&#46; The definitive pathological anatomy study revealed classic HL of a nodular sclerosis type in the presence of autoimmune thyroiditis&#44; with no apparent affect on the cervical lymph nodes&#46; Immunohistochemistry of Reed&#8211;Sternberg cells produced the following results&#58; CD15<span class="elsevierStyleSup">&#43;</span> CD30<span class="elsevierStyleSup">&#43;</span> CD20<span class="elsevierStyleSup">&#43;</span> &#40;weak expression&#41;&#44; CD79a<span class="elsevierStyleSup">&#8722;</span>&#44; MUM1<span class="elsevierStyleSup">&#43;</span> PAX5<span class="elsevierStyleSup">&#43;</span> and EBER<span class="elsevierStyleSup">&#43;</span>&#46; A gene rearrangement study of T cell receptor &#40;TCR&#41; genes and immunoglobulin heavy chain &#40;IgH&#41; antibodies was carried out by means of quantitative polymerase chain reaction &#40;PCR&#41;&#44; whose result was negative&#46; A fluorescence hybridization in situ &#40;FISH&#41; study for MALT-1 produced negative results&#46; A positron emission tomography&#8211;computed tomography &#40;PET&#8211;CT&#41; scan of the cervicothoracic area&#44; abdomen and pelvis was performed and revealed no hypermetabolic foci suggestive of active tumor disease&#46; Thus&#44; a diagnosis of primary thyroid gland LH &#40;Ann Arbor Stage Ie&#41; secondary to autoimmune thyroiditis was confirmed&#46; As a consequence&#44; ABVD &#40;Adriamycin&#44; Bleomycin&#44; Vinblastine and Dacarbazine&#41; chemotherapy was initiated&#46; It is now 8 months since surgery and the patient has completed four ABVD cycles&#46; A recent PET&#8211;CT scan revealed no hypermetabolic foci suggestive of active tumor disease&#44; therefore pointing to complete remission&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Approximately 75&#8211;80&#37; of thyroid HL patients are women&#44; in contrast to extrathyroid HL patients&#44; among which the incident rate is similar in both sexes&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The average age of patients is 40 years&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> which is lower than that of thyroid NHL patients&#44; who tend to be in their sixth decade of life&#46; In 80&#37; of thyroid HL cases&#44; there is a rapid increase of a uni- or bilateral cervical mass&#46; Other symptoms are shortness of breath &#40;65&#37;&#41; and dysphagia &#40;53&#37;&#41;&#46; Most patients have concomitant lymphadenopathy at the time of diagnosis&#46; What are known as B symptoms &#40;fever&#44; sweating&#44; loss of weight&#41; are frequent &#40;33&#37;&#41; and are considered a sign of bad prognosis&#46; The majority of subjects are euthyroid at the time of diagnosis&#44; while 30&#8211;40&#37; are hypothyroid&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Thyroid lymphoma can have different appearances when visualized by ultrasounds &#40;diffuse&#44; nodular or mixed<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>&#41;&#46; The diagnostic effectiveness of FNAB is variable&#46; According to different studies&#44; 50&#8211;80&#37; of thyroid lymphoma cases are diagnosed by FNAB&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> though this procedure should be backed up by other methods to confirm a diagnosis of HL&#46; For example&#44; a morphologic study should be carried out to confirm the presence of Reed&#8211;Sternberg cells&#46; In HL&#44; neoplasic Reed&#8211;Sternberg cells are in the minority &#40;less than 1&#37; of the cellularity&#41;&#44; while the majority are inflammatory cells &#40;lymphocytes&#44; histiocytes&#44; eosinophils and plasmatic cells<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a>&#41;&#46; Immunochemistry is also recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Reed&#8211;Sternberg cells express CD15 and CD30 in most cases&#44; and are normally negative for CD3 and CD45&#46; In a small number of cases&#44; a weak expression of different B lineage antigens can be detected&#44; such as CD20 &#40;as in the case of our patient&#41; and CD79a&#46; Moreover&#44; PAX-5&#44; another antigen associated with the B linage is expressed in 90&#37; of cases&#46; If there is absence of expression of CD30 and CD15 or an intense expression of CD20 is detected in the malignant cells&#44; a diagnosis of classic HL should be reconsidered and nodular lymphocyte-predominant Hodgkin&#39;s lymphoma &#40;NLPHL&#41; and a large-cell lymphoma &#40;LCL&#41; of cell-type T ruled out&#46; In the case of our patient&#44; the presence of Reed&#8211;Sternberg cells together with the expression of CD15 and CD30 and weak expression of CD20 confirmed a diagnosis of HL&#46; A differential diagnosis between HL and Hashimoto thyroiditis can be difficult for various reasons&#46; Hypocellularity&#44; a lack of Reed&#8211;Sternberg cells&#44; the presence of strong fibrosis or sclerosis&#44; and similarity between reactive cells &#40;activated lymphoblasts&#41; and Reed&#8211;Sternberg cells are all potentially confounding factors&#46; In addition&#44; the low incidence rate of thyroid gland HL and coexistence of thyroiditis and lymphoma can complicate matters&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In light of this&#44; a biopsy is normally required to determine HL&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> There is no consensus on whether a core biopsy or an open surgical biopsy is best&#44; as no randomized or prospective studies have been carried out to date&#46; Flow cytometry generally improves the accuracy of cytology in the diagnosis of NLH&#46; It allows the immunophenotype of lymphocytes and their origin &#40;B or T&#41; to be determined and reveals whether they are monoclonal or polyclonal&#44; although <span class="elsevierStyleItalic">&#954;</span>&#58; <span class="elsevierStyleItalic">&#955;</span> ratios can increase in many cases of thyroiditis&#44; particularly in the B CD10<span class="elsevierStyleSup">&#43;</span> cells of the germinal center&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Flow cytometry has seldom been used in cases of HL&#44; principally due to the low incidence rate of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In fact&#44; it does not help diagnosis&#44; as benign or reactivated lymphoid cells predominate in this type of lymphoma&#46; In our patient&#44; flow cytometry did not reveal any monoclonal component&#44; which ruled out LNH&#44; but not HL&#44; and so a biopsy was performed&#46; A molecular study can be useful when there are doubts about the diagnosis&#44; though its implementation is not essential&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> It detects clonality across genetic rearrangement and provides additional information in cases in which morphology and flow cytometry results are discrepant&#46; Lymphoid neoplasms are monoclonal and&#44; in most of these proliferations&#44; the rearranging of TCR and of IgH genes precedes malignant transformation&#46; Consequently&#44; all cells resulting from the same malignant progenitor cell share a rearranged DNA and express the same receptors &#40;a TCR or identical IgH&#41;&#46; For this reason&#44; analysis of TCR and IgH by means of PCR allows clonality of cell populations of B or T lymphoid cells to be detected&#46; In most cases of classic HL&#44; cloned rearrangements are not detected in TCR and IgH&#46; Monoclonal rearrangements of IgH genes have been detected only when micromanipulation techniques are carried out and the DNA extracted from isolated neoplasic cells is studied by means of this technique&#46; This confirms the B origin and malignant character &#40;clonal&#41; of Reed&#8211;Sternberg cells&#46; In our patient&#44; PCR did not detect gene rearrangements of TCR and IgH&#44; therefore allowing us to rule out the presence of a clonal population of mature B or T lymphocytes and&#44; consequently&#44; NLH&#46; We next performed a gene study for MALT lymphoma &#40;the most frequent thyroid lymphoma&#41;&#44; which proved negative&#46; The stage of a thyroid lymphoma should be determined by means of a CT or PET&#8211;CT scan&#46; The Ann Arbor system is used to establish a prognosis&#44; with most cases being diagnosed in stage Ie or IIe&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Evidence regarding treatment of thyroid lymphoma is limited and based on retrospective research studies&#44; none of which have been large&#44; pilot studies&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The role of surgery in the treatment of lymphoma of the thyroid gland is controversial&#59; as with all lymphomas&#44; this type is highly sensitive to chemotherapy and radiotherapy&#46; Indeed&#44; surgery does not appear to influence the prognosis&#46; Nevertheless&#44; it can be useful in cases in which airline obstruction exists and&#47;or the cytology is inconclusive&#46; When planning treatment&#44; it is necessary to bear in mind the stage and histology of the tumor&#46; In general&#44; all types of thyroid lymphoma are treated with a combination of chemotherapy and radiotherapy&#44; with the exception of the MALT type&#44; which has the best prognosis and is normally treated with only one of the afore mentioned therapies&#46; LH generally has a good prognosis&#46; In short&#44; we present the case of a woman with autoimmune thyroiditis who developed primary thyroid LH and responded well to chemotherapy&#46;</p></span></span>"
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Clinical communication
Hodgkin's lymphoma of the thyroid in a woman with autoimmune thyroiditis
Linfoma Hodgkin de tiroides en una mujer con tiroiditis autoinmune
O. Rubio-Puchola,b,
Autor para correspondencia
olallarubio@gmail.com

Corresponding author.
, S. Garzón-Pastora,b, V. Cortés-Vizcaínoc, I. Luna-Boqueraa,b, M. Gómez-Balaguera,b,d, A. Hernández-Mijaresa,b,d,e
a Endocrinology Department, University Hospital Dr Peset, Valencia, Spain
b Medicine Department, University of Valencia, Valencia, Spain
c Pathological Anatomy Department, University Hospital Dr Peset, Valencia, Spain
d Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Valencia, Spain
e Institute of Health Research INCLIVA, Valencia, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune thyroiditis is associated with the development of thyroid lymphoma&#44; and in particular mucosa-associated lymphoid tissue &#40;MALT&#41; lymphoma&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> though this type occurs in only 0&#46;5&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It has been reported that 20&#8211;30 years are needed for a lymphoma to develop as a result of autoimmune thyroiditis&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The association between thyroiditis and Hodgkin&#39;s lymphoma &#40;HL&#41; is more questionable&#44; and is difficult to clarify due to the low number of cases of HL that arise&#46; Nevertheless&#44; in a previous study of 21 HL patients&#44; 7 presented autoimmune thyroiditis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The hypothesis of an association between the two conditions is based on the fact that the thyroid gland does not contain native lymphoid tissue&#59; therefore&#44; intrathyroid lymphoid tissue develops because of the presence of autoimmune thyroiditis&#46; In this context&#44; antigenic stimulation of lymphocytes in autoimmune disorders may trigger a malignant transformation&#46; Primary extranodal HL accounts for less than 2&#37; of extranodal lymphomas<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and usually occurs due to the spreading of a contiguous lymphatic ganglion or hematogenous dissemination&#46; It is questionable whether this is actually a primary disease&#44; as it usually has an extrathyroid origin&#46; Moreover it is considerably infrequent&#44; with only 37 cases reported until now in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Its diagnosis is confirmed by the presence of Reed&#8211;Sternberg cells&#46; We report the case of a patient with autoimmune thyroiditis with a fast-growing thyroid nodule&#46; No evidence was detected of another tumor foci or adjacent lymphadenopathy&#44; which led us to consider a diagnosis of primary thyroid gland HL&#46; The peculiarity of this case lies in that&#44; despite suffering autoimmune thyroiditis&#44; the patient developed HL rather than MALT lymphoma&#44; which is the usual clinical course in such cases&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Patient</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 54-year-old woman was monitored for subclinical autoimmune hypothyroidism with anti-peroxidase antibodies 2933&#46;70<span class="elsevierStyleHsp" style=""></span>U per mililiter&#46; At the time&#44; she was receiving treatment with 75<span class="elsevierStyleHsp" style=""></span>&#956;g per day of levothyroxine&#46; Her thyroid function was controlled with TSH 1&#46;90<span class="elsevierStyleHsp" style=""></span>&#956;IU per mililiter and T4 free 1&#46;3<span class="elsevierStyleHsp" style=""></span>ng per deciliter&#46; The patient had no family history of thyroid pathology and no personal history of toxic substance abuse&#46; During her initial visit&#44; her cervical palpation was found to be normal&#44; and a thyroid ultrasound scan revealed a solid left thyroid nodule with a maximum diameter of 9<span class="elsevierStyleHsp" style=""></span>mm that was hypoechoic&#44; clearly defined&#44; avascular and without calcification&#46; According to current guidelines of clinical practice&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> fine needle-aspiration biopsy &#40;FNAB&#41; was not indicated&#46; Ultrasound was scheduled one year later and revealed no significant changes&#46; Three years later&#44; the thyroid lesion began growing rapidly&#44; demonstrating a palpable thyroid nodule with a maximum diameter of 2<span class="elsevierStyleHsp" style=""></span>cm&#46; Ultrasound revealed an increase in the size of the nodule to 17&#46;8<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>22&#46;6<span class="elsevierStyleHsp" style=""></span>mm&#44; and showed it to be solid&#44; occupying practically all the left thyroid lobe&#44; hypoechoic&#44; unstructured and heterogeneous&#44; with mixed vascularization and without microcalcifications &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In response to these developments&#44; FNAB was carried out and revealed atypically large and multinucleate lymphocytes with features of Reed&#8211;Sternberg cells&#44; which raised suspicions of lymphoma &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Given the difficulty in distinguishing between inflammatory and lymphoproliferative processes &#40;especially MALT-type LNH&#41; in a patient with autoimmune thyroiditis&#44; it was decided to repeat FNAB with flow cytometry&#46; Atypical lymphocytes were observed once again&#44; but there was no sign of infiltration due to lymphoma &#40;CD3<span class="elsevierStyleSup">&#43;</span> T lymphocytes were observed in 48&#37;&#44; of which 73&#37; were CD4<span class="elsevierStyleSup">&#43;</span> and 22&#37; were CD8<span class="elsevierStyleSup">&#43;</span>&#59; 44&#37; were polyclonal CD19<span class="elsevierStyleSup">&#43;</span> B lymphocytes without evidence of immature cells&#41;&#46; In light of these results&#44; a biopsy was carried out &#40;left hemithyroidectomy&#41; to confirm a suspected thyroid HL&#46; The intraoperative biopsy suggested autoimmune thyroiditis without any evidence of lymphoma&#46; The definitive pathological anatomy study revealed classic HL of a nodular sclerosis type in the presence of autoimmune thyroiditis&#44; with no apparent affect on the cervical lymph nodes&#46; Immunohistochemistry of Reed&#8211;Sternberg cells produced the following results&#58; CD15<span class="elsevierStyleSup">&#43;</span> CD30<span class="elsevierStyleSup">&#43;</span> CD20<span class="elsevierStyleSup">&#43;</span> &#40;weak expression&#41;&#44; CD79a<span class="elsevierStyleSup">&#8722;</span>&#44; MUM1<span class="elsevierStyleSup">&#43;</span> PAX5<span class="elsevierStyleSup">&#43;</span> and EBER<span class="elsevierStyleSup">&#43;</span>&#46; A gene rearrangement study of T cell receptor &#40;TCR&#41; genes and immunoglobulin heavy chain &#40;IgH&#41; antibodies was carried out by means of quantitative polymerase chain reaction &#40;PCR&#41;&#44; whose result was negative&#46; A fluorescence hybridization in situ &#40;FISH&#41; study for MALT-1 produced negative results&#46; A positron emission tomography&#8211;computed tomography &#40;PET&#8211;CT&#41; scan of the cervicothoracic area&#44; abdomen and pelvis was performed and revealed no hypermetabolic foci suggestive of active tumor disease&#46; Thus&#44; a diagnosis of primary thyroid gland LH &#40;Ann Arbor Stage Ie&#41; secondary to autoimmune thyroiditis was confirmed&#46; As a consequence&#44; ABVD &#40;Adriamycin&#44; Bleomycin&#44; Vinblastine and Dacarbazine&#41; chemotherapy was initiated&#46; It is now 8 months since surgery and the patient has completed four ABVD cycles&#46; A recent PET&#8211;CT scan revealed no hypermetabolic foci suggestive of active tumor disease&#44; therefore pointing to complete remission&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Approximately 75&#8211;80&#37; of thyroid HL patients are women&#44; in contrast to extrathyroid HL patients&#44; among which the incident rate is similar in both sexes&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The average age of patients is 40 years&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> which is lower than that of thyroid NHL patients&#44; who tend to be in their sixth decade of life&#46; In 80&#37; of thyroid HL cases&#44; there is a rapid increase of a uni- or bilateral cervical mass&#46; Other symptoms are shortness of breath &#40;65&#37;&#41; and dysphagia &#40;53&#37;&#41;&#46; Most patients have concomitant lymphadenopathy at the time of diagnosis&#46; What are known as B symptoms &#40;fever&#44; sweating&#44; loss of weight&#41; are frequent &#40;33&#37;&#41; and are considered a sign of bad prognosis&#46; The majority of subjects are euthyroid at the time of diagnosis&#44; while 30&#8211;40&#37; are hypothyroid&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Thyroid lymphoma can have different appearances when visualized by ultrasounds &#40;diffuse&#44; nodular or mixed<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>&#41;&#46; The diagnostic effectiveness of FNAB is variable&#46; According to different studies&#44; 50&#8211;80&#37; of thyroid lymphoma cases are diagnosed by FNAB&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> though this procedure should be backed up by other methods to confirm a diagnosis of HL&#46; For example&#44; a morphologic study should be carried out to confirm the presence of Reed&#8211;Sternberg cells&#46; In HL&#44; neoplasic Reed&#8211;Sternberg cells are in the minority &#40;less than 1&#37; of the cellularity&#41;&#44; while the majority are inflammatory cells &#40;lymphocytes&#44; histiocytes&#44; eosinophils and plasmatic cells<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a>&#41;&#46; Immunochemistry is also recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Reed&#8211;Sternberg cells express CD15 and CD30 in most cases&#44; and are normally negative for CD3 and CD45&#46; In a small number of cases&#44; a weak expression of different B lineage antigens can be detected&#44; such as CD20 &#40;as in the case of our patient&#41; and CD79a&#46; Moreover&#44; PAX-5&#44; another antigen associated with the B linage is expressed in 90&#37; of cases&#46; If there is absence of expression of CD30 and CD15 or an intense expression of CD20 is detected in the malignant cells&#44; a diagnosis of classic HL should be reconsidered and nodular lymphocyte-predominant Hodgkin&#39;s lymphoma &#40;NLPHL&#41; and a large-cell lymphoma &#40;LCL&#41; of cell-type T ruled out&#46; In the case of our patient&#44; the presence of Reed&#8211;Sternberg cells together with the expression of CD15 and CD30 and weak expression of CD20 confirmed a diagnosis of HL&#46; A differential diagnosis between HL and Hashimoto thyroiditis can be difficult for various reasons&#46; Hypocellularity&#44; a lack of Reed&#8211;Sternberg cells&#44; the presence of strong fibrosis or sclerosis&#44; and similarity between reactive cells &#40;activated lymphoblasts&#41; and Reed&#8211;Sternberg cells are all potentially confounding factors&#46; In addition&#44; the low incidence rate of thyroid gland HL and coexistence of thyroiditis and lymphoma can complicate matters&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In light of this&#44; a biopsy is normally required to determine HL&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> There is no consensus on whether a core biopsy or an open surgical biopsy is best&#44; as no randomized or prospective studies have been carried out to date&#46; Flow cytometry generally improves the accuracy of cytology in the diagnosis of NLH&#46; It allows the immunophenotype of lymphocytes and their origin &#40;B or T&#41; to be determined and reveals whether they are monoclonal or polyclonal&#44; although <span class="elsevierStyleItalic">&#954;</span>&#58; <span class="elsevierStyleItalic">&#955;</span> ratios can increase in many cases of thyroiditis&#44; particularly in the B CD10<span class="elsevierStyleSup">&#43;</span> cells of the germinal center&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Flow cytometry has seldom been used in cases of HL&#44; principally due to the low incidence rate of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In fact&#44; it does not help diagnosis&#44; as benign or reactivated lymphoid cells predominate in this type of lymphoma&#46; In our patient&#44; flow cytometry did not reveal any monoclonal component&#44; which ruled out LNH&#44; but not HL&#44; and so a biopsy was performed&#46; A molecular study can be useful when there are doubts about the diagnosis&#44; though its implementation is not essential&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> It detects clonality across genetic rearrangement and provides additional information in cases in which morphology and flow cytometry results are discrepant&#46; Lymphoid neoplasms are monoclonal and&#44; in most of these proliferations&#44; the rearranging of TCR and of IgH genes precedes malignant transformation&#46; Consequently&#44; all cells resulting from the same malignant progenitor cell share a rearranged DNA and express the same receptors &#40;a TCR or identical IgH&#41;&#46; For this reason&#44; analysis of TCR and IgH by means of PCR allows clonality of cell populations of B or T lymphoid cells to be detected&#46; In most cases of classic HL&#44; cloned rearrangements are not detected in TCR and IgH&#46; Monoclonal rearrangements of IgH genes have been detected only when micromanipulation techniques are carried out and the DNA extracted from isolated neoplasic cells is studied by means of this technique&#46; This confirms the B origin and malignant character &#40;clonal&#41; of Reed&#8211;Sternberg cells&#46; In our patient&#44; PCR did not detect gene rearrangements of TCR and IgH&#44; therefore allowing us to rule out the presence of a clonal population of mature B or T lymphocytes and&#44; consequently&#44; NLH&#46; We next performed a gene study for MALT lymphoma &#40;the most frequent thyroid lymphoma&#41;&#44; which proved negative&#46; The stage of a thyroid lymphoma should be determined by means of a CT or PET&#8211;CT scan&#46; The Ann Arbor system is used to establish a prognosis&#44; with most cases being diagnosed in stage Ie or IIe&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Evidence regarding treatment of thyroid lymphoma is limited and based on retrospective research studies&#44; none of which have been large&#44; pilot studies&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The role of surgery in the treatment of lymphoma of the thyroid gland is controversial&#59; as with all lymphomas&#44; this type is highly sensitive to chemotherapy and radiotherapy&#46; Indeed&#44; surgery does not appear to influence the prognosis&#46; Nevertheless&#44; it can be useful in cases in which airline obstruction exists and&#47;or the cytology is inconclusive&#46; When planning treatment&#44; it is necessary to bear in mind the stage and histology of the tumor&#46; In general&#44; all types of thyroid lymphoma are treated with a combination of chemotherapy and radiotherapy&#44; with the exception of the MALT type&#44; which has the best prognosis and is normally treated with only one of the afore mentioned therapies&#46; LH generally has a good prognosis&#46; In short&#44; we present the case of a woman with autoimmune thyroiditis who developed primary thyroid LH and responded well to chemotherapy&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thyroid ultrasound scan&#46; &#40;a&#41; Right thyroid lobe with typical echogenicity of autoimmune thyroiditis and no nodular formations&#46; &#40;b&#41; Left thyroid lobe occupied by thyroid nodule&#46; &#40;c&#41; Ecodoppler of the left thyroid nodule showing mixed vascularization&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; FNAB of the left thyroid nodule&#46; Slight increase in size with abundant lymphocytes and absence of thyroid follicles&#46; &#40;b&#41; FNAB of the left thyroid nodule&#46; Detail of the lymphoid population&#58; predominance of small lymphocytes and presence of a large Reed&#8211;Sternberg cell with three nuclei and nucleolus&#46; &#40;c&#41; Thyroid biopsy&#46; Reed&#8211;Sternberg cells positive for CD30&#46;</p>"
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        "texto" => "<p id="par0025" class="elsevierStylePara elsevierViewall">We thank Brian Normanly for his editorial assistance&#46;</p>"
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