Primary thyroid lymphoma: Difference between revisions

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'''To review the wikidoc page on [[thyroid cancer]] , [[Thyroid cancer|click here]].<br>
{{SI}}
== Overview ==
== Overview ==
Thyroid lymphomas may be classified according to type of cells into 6 subtypes: non–Hodgkin's B-cell lymphomas, [[Hodgkin's lymphoma]], diffuse large B-cell lymphoma with marginal zone, [[Marginal zone B-cell lymphoma|diffuse large B-cell lymphoma without marginal zone]], [[MALT lymphoma]], and [[follicular lymphoma]]. Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas.<ref name=Radiopaedia 2015 Thyroid lymphoma>{{cite web | title = Radiopedia 2015 Thyroid lymphoma [Dr Henry Knipe]| url = http://radiopaedia.org/articles/thyroid-lymphoma }}</ref>. ''BRAF'' and ''NRAS'' mutations are asssociated with thyroid lymphoma. Thyroid lymphoma is rare with an incidence of 1-2 per 100,0000. The factors of poor [[prognosis]] for patients with thyroid lymphoma are advanced stage of the [[tumor]], large size  (>10 cm) as well as spreading to [[mediastinum]]. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years. Symptoms of thyroid lymphoma include painless rapidly growing [[neck]] mass, [[hoarseness]], and difficulty in swallowing. [[CT|Neck CT]] scan may be helpful in the [[diagnosis]] of thyroid lymphoma. Findings on [[CT]] scan suggestive of thyroid lymphoma is hypodense or heterogenous enhancement in the thyroid gland. [[Biopsy]] may be helpful in the [[diagnosis]] of thyroid lymphoma. Findings on [[biopsy]] suggestive of thyroid lymphoma include lymphoepithelial leision and [[lymphocytes]]. ''Combined modality therapy'' is the most common approach for the initial treatment of thyroid lymphomas. The CHOP regimen ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]] and [[prednisone]]) has been showed high effectiveness for many types of thyroid lymphoma. However, it is suggested to perform [[radiation therapy]] only for [[MALT lymphoma]] resulting a 96% complete response, with only a 30% relapse rate. Surgical treatment might be performed for patients with thyroid lymphoma in addition to [[chemotherapy]] and [[radiation]], particularly for [[MALT lymphoma]].
Primary thyroid lymphoma is almost always of [[B cell]] lineage. Preexisting [[Hashimoto thyroiditis]] is a known [[risk factor]] for the primary thyroid lymphoma and is present among half of the [[patients]]. Thyroid lymphoma is rare with an [[incidence]] of 0.1-0.2 per 100,000. Common symptoms of primary thyroid lymphoma include painless enlarging  [[neck mass]], [[hoarseness]], [[dysphagia|Difficulty swallowing]], and [[dyspnea|Difficulty breathing]]. Classic [[B symptoms]] of [[lymphoma]] occurs in less than 20% of [[patients]]. Physical examination findings consistent with the [[diagnosis]] of thyroid lymphoma include abnormal texture of [[thyroid gland]] in palpation as well as cervical and/or supraclavicular [[lymphadenopathy]]. There is no [[laoratory findings]] specific for the [[diagnosis]] of primary thyroid lymphoma. Thyroid lymphoma may be difficult to be differentiated from [[Hashimoto thyroiditis]]. MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma. The CHOP regimen ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]] and [[prednisone]]) has been showed high effectiveness for many types of thyroid lymphoma. [[Radiotherapy]] is indicated in case of [[patients]] with localized, extranodal, [[marginal zone lymphoma]] of the [[thyroid]] or other indolent [[histologies]] (eg, [[follicular lymphoma]], [[small lymphocytic lymphoma]]).[[Surgical]] intervention might be performed for [[patients]] with thyroid lymphoma in addition to [[chemotherapy]] and [[radiation]], particularly for [[MALT]] lymphomas.
==Historical Perspective==
* There is no data available on historical perspective of primary thyroid lymphoma.
==Classification==
==Classification==
Thyroid lymphomas may be classified according to type of cells into 6 subtypes: non–Hodgkin's B-cell lymphomas, [[Hodgkin's lymphoma]], diffuse large B-cell lymphoma with marginal zone, [[Marginal zone B-cell lymphoma|diffuse large B-cell lymphoma without marginal zone]], [[MALT lymphoma|marginal zone В-cell lymphoma of mucosa-associated lymphoid tissue]], and follicular lymphoma.
* Primary thyroid lymphoma is almost always of [[B cell]] lineage.<ref name="pmid1929820">{{cite journal |vauthors=Skarsgard ED, Connors JM, Robins RE |title=A current analysis of primary lymphoma of the thyroid |journal=Arch Surg |volume=126 |issue=10 |pages=1199–203; discussion 1203–4 |date=October 1991 |pmid=1929820 |doi=10.1001/archsurg.1991.01410340037006 |url=}}</ref><ref name="pmid8838117">{{cite journal |vauthors=Pedersen RK, Pedersen NT |title=Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study |journal=Histopathology |volume=28 |issue=1 |pages=25–32 |date=January 1996 |pmid=8838117 |doi=10.1046/j.1365-2559.1996.268311.x |url=}}</ref><ref name="Vardell NobleErmann2019">{{cite journal|last1=Vardell Noble|first1=Victoria|last2=Ermann|first2=Daniel A|last3=Griffin|first3=Emily K|last4=Silberstein|first4=Peter T|title=Primary Thyroid Lymphoma: An Analysis of the National Cancer Database |journal=Cureus|year=2019|issn=2168-8184|doi=10.7759/cureus.4088}}</ref>
 
* According to a recent survey, it is of non-hodgkin origin in 98% of the cases.
* Thyroid lymphomas may be classified according to type of [[cells]] into subtypes:  
** [[Diffuse large B-cell lymphoma with marginal zone]] which is the most common subtype.
** [[Marginal zone B-cell lymphoma|diffuse large B-cell lymphoma without marginal zone]], the second most common subtype.
** [[MALT lymphoma|marginal zone В-cell lymphoma of mucosa-associated lymphoid tissue]]
** [[Follicular lymphoma]]
== Pathophysiology==
== Pathophysiology==
* Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas.<ref name=Radiopaedia 2015 Thyroid lymphoma
* The [[thyroid gland]] may be affected primarily or secondary to lymphoma elsewhere.
>{{cite web | title = Radiopedia 2015 Thyroid lymphoma [Dr Henry Knipe]| url = http://radiopaedia.org/articles/thyroid-lymphoma }}</ref>  
* Thyroid lymphoma refers to the [[lymphoma]] that primarily originates from the [[thyroid]] [[tissue]].
* The [[thyroid]] may be affected primarily or secondary to lymphoma elsewhere.  
* Thyroid lymphoma is associated with [[hashimoto’s thyroiditis]].<ref name="pmid10375088">{{cite journal |vauthors=Ansell SM, Grant CS, Habermann TM |title=Primary thyroid lymphoma |journal=Semin. Oncol. |volume=26 |issue=3 |pages=316–23 |date=June 1999 |pmid=10375088 |doi= |url=}}</ref>
* There is increased risk with chronic inflammatory conditions.
* It is understood that thyroid lymphoma is the result of chronic antigenic stimulation secondary to the [[autoimmune disorder]].
=== Genetics ===
* [[Hashimoto thyroiditis]] causes chronic proliferation of [[lymphoid tissue]] which eventually leads to a [[mutation]] and result in lymphoma.
* ''BRAF'' and ''NRAS'' mutations are asssociated with thyroid lymphoma.
* BRAF and NRAS mutations are associated with thyroid lymphoma.<ref name="AggarwalSwerdlow2012">{{cite journal|last1=Aggarwal|first1=Nidhi|last2=Swerdlow|first2=Steven H|last3=Kelly|first3=Lindsey M|last4=Ogilvie|first4=Jennifer B|last5=Nikiforova|first5=Mariana N|last6=Sathanoori|first6=Malini|last7=Nikiforov|first7=Yuri E|title=Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas|journal=Modern Pathology|volume=25|issue=9|year=2012|pages=1203–1211|issn=0893-3952|doi=10.1038/modpathol.2012.73}}</ref>
* MAPK pathway mutations are associated with B cell thyroid lymohoma.<ref name="AggarwalSwerdlow2012">{{cite journal|last1=Aggarwal|first1=Nidhi|last2=Swerdlow|first2=Steven H|last3=Kelly|first3=Lindsey M|last4=Ogilvie|first4=Jennifer B|last5=Nikiforova|first5=Mariana N|last6=Sathanoori|first6=Malini|last7=Nikiforov|first7=Yuri E|title=Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas|journal=Modern Pathology|volume=25|issue=9|year=2012|pages=1203–1211|issn=0893-3952|doi=10.1038/modpathol.2012.73}}</ref>
* MAPK pathway [[mutations]] are associated with [[B cell]] thyroid lymphoma.
 
* Macroscopic Findings associated with the [[diagnosis]] of primary thyroid lymphoma include:<ref name="DundarSarkut2016">{{cite journal|last1=Dundar|first1=Halit Ziya|last2=Sarkut|first2=Pinar|last3=Kirdak|first3=Turkay|last4=Korun|first4=Nusret|title=Primary thyroid lymphoma|journal=Turkish Journal of Surgery|volume=32|issue=1|year=2016|pages=75–77|issn=13000705|doi=10.5152/UCD.2015.2935}}</ref>
=== Associated Conditions===
** Variable size
* [[Hashimoto’s thyroiditis]]
** Rubbery [[mass]] with fish flesh appearance
 
* On microscopic [[histopathological]] analysis, characteristic findings of thyroid lymphoma are:
===Gross Pathology===
* Variable size
* Rubbery mass with fish flesh appearance
 
===Microscopic Pathology===
* On microscopic histopathological analysis, the following are characteristic findings of thyroid lymphoma
:* Lymphoepithelial lesion  
:* Lymphoepithelial lesion  
:* [[Plasma cells]]
:* [[Plasma cells]]
:* Thyroid parenchyma displaced by [[lymphocytes]]
:* [[Thyroid]] parenchyma displaced by [[lymphocytes]]
 
== Causes ==
* The exact [[cause]] of primary thyroid lymphoma is unclear. However, [[Hashimoto thyroiditis]] is a known [[risk factor]] for this [[disorder]].<ref name="pmid8838117">{{cite journal |vauthors=Pedersen RK, Pedersen NT |title=Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study |journal=Histopathology |volume=28 |issue=1 |pages=25–32 |date=January 1996 |pmid=8838117 |doi=10.1046/j.1365-2559.1996.268311.x |url=}}</ref>
== Risk Factors ==
* Preexisting [[Hashimoto thyroiditis]] is a known [[risk factor]] for the primary thyroid lymphoma and is present among half of the [[patients]].<ref name="pmid3838363">{{cite journal |vauthors=Holm LE, Blomgren H, Löwhagen T |title=Cancer risks in patients with chronic lymphocytic thyroiditis |journal=N. Engl. J. Med. |volume=312 |issue=10 |pages=601–4 |date=March 1985 |pmid=3838363 |doi=10.1056/NEJM198503073121001 |url=}}</ref><ref name="pmid3141260">{{cite journal |vauthors=Hyjek E, Isaacson PG |title=Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis |journal=Hum. Pathol. |volume=19 |issue=11 |pages=1315–26 |date=November 1988 |pmid=3141260 |doi=10.1016/s0046-8177(88)80287-9 |url=}}</ref><ref name="pmid8838117">{{cite journal |vauthors=Pedersen RK, Pedersen NT |title=Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study |journal=Histopathology |volume=28 |issue=1 |pages=25–32 |date=January 1996 |pmid=8838117 |doi=10.1046/j.1365-2559.1996.268311.x |url=}}</ref>
* The evidence for such [[association]] is the higher [[incidence]] of thyroid lymphoma in areas with a higher [[prevalence]] of [[Hashimoto thyroiditis]].
==Screening==
* There is insufficient evidence to recommend routine screening for primary thyroid lymphoma.<ref name="urlExit Disclaimer - US Preventive Services Task Force">{{cite web |url=https://www.uspreventiveservicestaskforce.org/Page/Name/exit-disclaimer |title=Exit Disclaimer - US Preventive Services Task Force |format= |work= |accessdate=}}</ref>
== Differentiating thyroid lymphoma from Other Diseases ==
* Primary thyroid lymphoma should be differentiated from other [[disorders]] causing enlarging [[thyroid masses]], and compression [[symptoms]]. These [[disorders]] include other [[thyroid cancers]] as well as [[thyroid follicular adenomas]].
* For more information on primary thyroid lymphoma, please [[anaplastic thyroid cancer differential diagnosis|click here]].
== Epidemiology and Demographics ==
== Epidemiology and Demographics ==
===Incidence===
* Thyroid lymphoma is rare with an [[incidence]] of 0.1-0.2 per 100,000.<ref>{{cite journal|doi=10.1046/j.1365-2559.1996.268311.x.}}</ref>
* Thyroid lymphoma is rare with an incidence of 1-2 per 100,0000
* It typically presents between 50-70 years of age.<ref name="HolmBlomgren1985">{{cite journal|last1=Holm|first1=Lars-Erik|last2=Blomgren|first2=Henric|last3=Löwhagen|first3=Torsten|title=Cancer Risks in Patients with Chronic Lymphocytic Thyroiditis|journal=New England Journal of Medicine|volume=312|issue=10|year=1985|pages=601–604|issn=0028-4793|doi=10.1056/NEJM198503073121001}}</ref>
===Age===
* Females are more commonly affected with anaplastic thyroid cancer than males. The females to male ratio are approximately 2-8 to 1.
* It typically presents between 50-70 years of age
===Gender===
* Females are more commonly affected with anaplastic thyroid cancer than males. The females to male ratio is approximately 3 to 1.
 
== Natural History, Complications and Prognosis==
== Natural History, Complications and Prognosis==
* The factors of poor prognosis for patients with thyroid lymphoma are advanced stage of the tumor, large size  (>10 cm) as well as spreading to mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years.
* Common complications of primary thyroid lymphoma include [[Vocal cord paralysis]], [[Dyspnea]], [[Dysphagia]] and [[Metastasis]].<ref name="HedhiliKedous2015">{{cite journal|last1=Hedhili|first1=F.|last2=Kedous|first2=S.|last3=Jbali|first3=S.|last4=Attia|first4=Z.|last5=Dhambri|first5=S.|last6=Touati|first6=S.|last7=Chebbi|first7=A. Goucha|last8=El May|first8=A.|last9=Gritli|first9=S.|title=Primary thyroid lymphoma: Case report and review of the literature|journal=Egyptian Journal of Ear, Nose, Throat and Allied Sciences|volume=16|issue=2|year=2015|pages=171–173|issn=20900740|doi=10.1016/j.ejenta.2015.05.002}}</ref>
===Complications===
* Factors associated with poor [[prognosis]] for patients with thyroid lymphoma are an advanced stage of the [[tumor]], large size  (>10 cm) as well as spreading to [[mediastinum]].
* Vocal cord paralysis
== Diagnosis ==
* [[Dyspnea]]
=== Diagnostic Study of Choice ===
* [[Dysphagia]]
===Diagnostic Criteria===
* [[Metastasis]]
* There are no established criteria for the [[diagnosis]] of primary thyroid lymphoma.
===Prognosis===
* [[ultrasound]] guided [[fine needle aspiration]] is used for he initial [[diagnosis]] of [[thyroid nodule]] [[histology]].
* [[Prognosis]] depends on the histological grade of the tumor
* [[MALT lymphoma]] have better prognosis with a slower progressive course
* Diffuse large cell lymphomas have worse prognosis and aggressive course
* 5 year survival rate varies between 50-60%<ref name="HedhiliKedous2015">{{cite journal|last1=Hedhili|first1=F.|last2=Kedous|first2=S.|last3=Jbali|first3=S.|last4=Attia|first4=Z.|last5=Dhambri|first5=S.|last6=Touati|first6=S.|last7=Chebbi|first7=A. Goucha|last8=El May|first8=A.|last9=Gritli|first9=S.|title=Primary thyroid lymphoma: Case report and review of the literature|journal=Egyptian Journal of Ear, Nose, Throat and Allied Sciences|volume=16|issue=2|year=2015|pages=171–173|issn=20900740|doi=10.1016/j.ejenta.2015.05.002}}</ref>
 
===Staging===
===Staging===
* Staging of thyroid lymphoma is showed in the table below
* Staging of thyroid lymphoma is showed in the table below:<ref>{{cite book | last = Edge | first = Stephen | title = AJCC cancer staging manual | publisher = Springer | location = New York | year = 2010 | isbn = 978-0-387-88440-0 }</ref><br>
{| class="wikitable"
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+'''''Thyroid lymphoma staging'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Stage}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Characteristics}}
|-
|-
! Stage !! Characteristics
! style="background: #DCDCDC;" |IE
! style="background: #F5F5F5;" |Lymphoma is located within the thyroid
|-
|-
| || Lymphoma is located within the thyroid
! style="background: #DCDCDC;" |2E
! style="background: #F5F5F5;" |Lymphoma is located within the thyroid and regional  lymph-nodes
|-
|-
| 2Е || Lymphoma is located within the thyroid and regional  lymph-nodes
! style="background: #DCDCDC;" |3E
! style="background: #F5F5F5;" |Lymphoma is located at both sides of diaphragm
|-
|-
| 3Е || Lymphoma is located at both sides of diaphragm
! style="background: #DCDCDC;" |4E
|-
! style="background: #F5F5F5;" |Dissemination of lymphoma  
| 4Е || Dissemination of lymphoma  
|}
|}
 
===History and Symptoms===
===Diagnostic Criteria===
* Common symptoms of primary thyroid lymphoma include:<ref name="KatnaShet2013">{{cite journal|last1=Katna|first1=Rakesh|last2=Shet|first2=Tanuja|last3=Sengar|first3=Manju|last4=Menon|first4=Hari|last5=Laskar|first5=Siddharth|last6=Prabhash|first6=Kumar|last7=D'Cruz|first7=Anil|last8=Nair|first8=Reena|title=Clinicopathologic study and outcome analysis of thyroid lymphomas: Experience from a tertiary cancer center|journal=Head & Neck|volume=35|issue=2|year=2013|pages=165–171|issn=10433074|doi=10.1002/hed.22928}}</ref><ref name="pmid8838117">{{cite journal |vauthors=Pedersen RK, Pedersen NT |title=Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study |journal=Histopathology |volume=28 |issue=1 |pages=25–32 |date=January 1996 |pmid=8838117 |doi=10.1046/j.1365-2559.1996.268311.x |url=}}</ref>
Thyroid lymphoma shows a diagnostic and therapeutic challenge in many cases, because some manifestation patterns are similar to [[anaplastic thyroid carcinoma]] (ATC). Performance of fine needle aspiration biopsy has helped to distinguish these two entities preoperatively.
** Painless enlarging  [[neck mass]]
 
** [[Hoarseness]]
===History===
** [[Dysphagia|Difficulty swallowing]]
A directed history should be obtained to ascertain
** [[Dyspnea|Difficulty breathing]]
=== Symptoms ===
* Classic [[B symptoms]] of [[lymphoma]] occurs in less than 20% of [[patients]].
*Painless [[neck mass]]
*[[Hoarseness]]
*[[Dysphagia|Difficulty swallowing]]
*[[Dyspnea|Difficulty breathing]]
 
=== Physical Examination ===
=== Physical Examination ===
====Throat ====
* Common physical examination findings of primary thyroid lymphoma include:<ref name="pmid1555984">{{cite journal |vauthors=Logue JP, Hale RJ, Stewart AL, Duthie MB, Banerjee SS |title=Primary malignant lymphoma of the thyroid: a clinicopathological analysis |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=22 |issue=5 |pages=929–33 |date=1992 |pmid=1555984 |doi=10.1016/0360-3016(92)90790-o |url=}}</ref><ref name="pmid3759532">{{cite journal |vauthors=Tupchong L, Hughes F, Harmer CL |title=Primary lymphoma of the thyroid: clinical features, prognostic factors, and results of treatment |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=12 |issue=10 |pages=1813–21 |date=October 1986 |pmid=3759532 |doi=10.1016/0360-3016(86)90324-x |url=}}</ref>
* Rapidly growing painless mass in the neck
** [[Thyroid]] has a firm to hard texture in palpation and is fixed to the surronding [[tissues]].
* [[Lymphadenopathy]]
** Cervical and/or supraclavicular [[lymphadenopathy]] may also be present.
====CT ====
=== Laboratory Findings ===
* [[Goitre]], which is hypodense to adjacent muscle
* There is no [[laoratory findings]] specific for the [[diagnosis]] of primary thyroid lymphoma.<ref name="pmid8838117">{{cite journal |vauthors=Pedersen RK, Pedersen NT |title=Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study |journal=Histopathology |volume=28 |issue=1 |pages=25–32 |date=January 1996 |pmid=8838117 |doi=10.1046/j.1365-2559.1996.268311.x |url=}}</ref>
* Heterogeneous enhancement but still less than adjacent muscle
* Laboratory findings helpful for the [[diagnosis]] of [[Hashimoto thyroiditis]] include high serum concentrations of [[antithyroid peroxidase]] or [[antithyroglobulin antibodies]].
=== Electrocardiogram ===
* There are no [[ECG]] findings associated with primary thyroid lymphoma.
=== X-Ray ===
* There are no [[x-ray]] findings associated with primary thyroid lymphoma.
=== Echocardiography or Ultrasound ===
* Thyroid lymphoma may be difficult to be differentiated from [[Hashimoto thyroiditis]].<ref name="pmid7890856">{{cite journal |vauthors=Takashima S, Nomura N, Noguchi Y, Matsuzuka F, Inoue T |title=Primary thyroid lymphoma: evaluation with US, CT, and MRI |journal=J Comput Assist Tomogr |volume=19 |issue=2 |pages=282–8 |date=1995 |pmid=7890856 |doi= |url=}}</ref>
* Three [[sonographic]] patterns are reported and include [[nodular]], diffuse and mixed subtypes.<ref name="pmid17042683">{{cite journal |vauthors=Ota H, Ito Y, Matsuzuka F, Kuma S, Fukata S, Morita S, Kobayashi K, Nakamura Y, Kakudo K, Amino N, Miyauchi A |title=Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid |journal=Thyroid |volume=16 |issue=10 |pages=983–7 |date=October 2006 |pmid=17042683 |doi=10.1089/thy.2006.16.983 |url=}}</ref>
* Nodular lymphoma has a very uniform and hypoechoic pattern that may be sufficiently hypoechoic to be pseudo-cystic. The border of the [[tumor]] is well defined, and the borderline may be "broccoli-like" or "coastline-like" irregular.
* Diffuse lymphoma has an indistinguishable border from non-lymphomatous part of [[thyroid]] and otherwise is similar to [[goiter]]. Internal echoes are also of exceedingly low intensity.
* The mixed lymphoma showes multiple, patchy hypoechoic [[lesions]], with enhanced posterior echoes in each [[lesion]].
=== CT ===
* CT findings associated with the diagnosis of primary thyroid lymphoma include solitary nodule, multiple nodules, and diffuse enlargement.<ref name="pmid12758117">{{cite journal |vauthors=Kim HC, Han MH, Kim KH, Jae HJ, Lee SH, Kim SS, Kim KH, Chang KH |title=Primary thyroid lymphoma: CT findings |journal=Eur J Radiol |volume=46 |issue=3 |pages=233–9 |date=June 2003 |pmid=12758117 |doi=10.1016/s0720-048x(02)00134-1 |url=}}</ref>
* A characteristic finding ob CT imaging is "donut sign," observed when the lymphoma completely encircles the trachea.
==== MRI ====
==== MRI ====
* T1/T2: iso- to hyperintense
* MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma.<ref name="pmid7890856">{{cite journal |vauthors=Takashima S, Nomura N, Noguchi Y, Matsuzuka F, Inoue T |title=Primary thyroid lymphoma: evaluation with US, CT, and MRI |journal=J Comput Assist Tomogr |volume=19 |issue=2 |pages=282–8 |date=1995 |pmid=7890856 |doi= |url=}}</ref>
* Pseudocapsule may be present
=== Other Imaging Findings ===
==== Echocardiography or Ultrasound ====
* There are no other [[imaging]] findings associated with primary thyroid lymphoma.
* Three patterns have been described: nodular (hypoechoic mass), diffuse (mixed echotexture) or mixed. Calcifications are uncommon.
=== Other Diagnostic Studies ===
====Biopsy====
* There are no other [[diagnostic]] studies associated with primary thyroid lymphoma.
[[Biopsy]] may be helpful in the diagnosis of thyroid lymphoma. Findings on biopsy suggestive of thyroid lymphoma include lymphoepithelial leision and [[lymphocyte]].
== Treatment ==
== Treatment ==
=== Pharmacotherapy ===
=== Medical Therapy ===
Combined modality therapy is the most common approach for the initial treatment of thyroid lymphomas. The CHOP regimen ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]] and [[prednisone]]) has been showed high effectiveness for many types of thyroid lymphoma. However, it is suggested to perform radiation therapy only for MALT resulting a 96% complete response, with only a 30% relapse rate.
* Combined therapy with chemoradiation is indicated in [[patients]] with localized, early-stage [[diffuse large B cell lymphoma]].<ref name="pmid24501704">{{cite journal |vauthors=Cha H, Kim JW, Suh CO, Kim JS, Cheong JW, Lee J, Keum KC, Lee CG, Cho J |title=Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study |journal=Radiat Oncol J |volume=31 |issue=4 |pages=177–84 |date=December 2013 |pmid=24501704 |pmc=3912230 |doi=10.3857/roj.2013.31.4.177 |url=}}</ref>
==== Acute Pharmacotherapies ====
* The CHOP regimen ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]] and [[prednisone]]) has been showed high effectiveness for many types of thyroid lymphoma.
* [[Steroid]]
* [[Radiotherapy]] is indicated in case of [[patients]] with localized, extranodal, [[marginal zone lymphoma]] of the [[thyroid]] or other indolent [[histologies]] (eg, [[follicular lymphoma]], [[small lymphocytic lymphoma]]).
==== Chronic Pharmacotherapies ====
=== Surgery ===  
* [[Radiotherapy]]
* [[Surgery]] is not the treatment of choice for primary thyroid lymphoma.<ref name="PeixotoCorreia Pinto2017">{{cite journal|last1=Peixoto|first1=Rita|last2=Correia Pinto|first2=João|last3=Soares|first3=Virgínia|last4=Koch|first4=Pedro|last5=Taveira Gomes|first5=António|title=Primary thyroid lymphoma: A case report and review of the literature|journal=Annals of Medicine and Surgery|volume=13|year=2017|pages=29–33|issn=20490801|doi=10.1016/j.amsu.2016.12.023}}</ref>
=== Surgery and Device Based Therapy ===  
* [[Surgical]] intervention might be performed for [[patients]] with thyroid lymphoma in addition to [[chemotherapy]] and [[radiation]], particularly for [[MALT]] lymphomas.
Surgical treatment might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for [[MALT]] lymphomas.
=== Primary Prevention ===
* [[Thyroidectomy]] (rarely)
* There are no established measures for the [[primary prevention]] of primary thyroid lymphoma.
* Radical left neck dissection
=== Secondary Prevention ===
* [[Tracheostomy]] is indicated for vocal cord paralysis
* There are no established measures for the secondary prevention of primary thyroid lymphoma.
 
==References==
==References==
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Overview

Primary thyroid lymphoma is almost always of B cell lineage. Preexisting Hashimoto thyroiditis is a known risk factor for the primary thyroid lymphoma and is present among half of the patients. Thyroid lymphoma is rare with an incidence of 0.1-0.2 per 100,000. Common symptoms of primary thyroid lymphoma include painless enlarging neck mass, hoarseness, Difficulty swallowing, and Difficulty breathing. Classic B symptoms of lymphoma occurs in less than 20% of patients. Physical examination findings consistent with the diagnosis of thyroid lymphoma include abnormal texture of thyroid gland in palpation as well as cervical and/or supraclavicular lymphadenopathy. There is no laoratory findings specific for the diagnosis of primary thyroid lymphoma. Thyroid lymphoma may be difficult to be differentiated from Hashimoto thyroiditis. MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been showed high effectiveness for many types of thyroid lymphoma. Radiotherapy is indicated in case of patients with localized, extranodal, marginal zone lymphoma of the thyroid or other indolent histologies (eg, follicular lymphoma, small lymphocytic lymphoma).Surgical intervention might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas.

Historical Perspective

  • There is no data available on historical perspective of primary thyroid lymphoma.

Classification

Pathophysiology

Causes

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for primary thyroid lymphoma.[9]

Differentiating thyroid lymphoma from Other Diseases

Epidemiology and Demographics

  • Thyroid lymphoma is rare with an incidence of 0.1-0.2 per 100,000.[10]
  • It typically presents between 50-70 years of age.[11]
  • Females are more commonly affected with anaplastic thyroid cancer than males. The females to male ratio are approximately 2-8 to 1.

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Diagnostic Criteria

Staging

  • Staging of thyroid lymphoma is showed in the table below:[13]
Thyroid lymphoma staging
Stage Characteristics
IE Lymphoma is located within the thyroid
2E Lymphoma is located within the thyroid and regional lymph-nodes
3E Lymphoma is located at both sides of diaphragm
4E Dissemination of lymphoma

History and Symptoms

Physical Examination

  • Common physical examination findings of primary thyroid lymphoma include:[15][16]
    • Thyroid has a firm to hard texture in palpation and is fixed to the surronding tissues.
    • Cervical and/or supraclavicular lymphadenopathy may also be present.

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with primary thyroid lymphoma.

X-Ray

  • There are no x-ray findings associated with primary thyroid lymphoma.

Echocardiography or Ultrasound

  • Thyroid lymphoma may be difficult to be differentiated from Hashimoto thyroiditis.[17]
  • Three sonographic patterns are reported and include nodular, diffuse and mixed subtypes.[18]
  • Nodular lymphoma has a very uniform and hypoechoic pattern that may be sufficiently hypoechoic to be pseudo-cystic. The border of the tumor is well defined, and the borderline may be "broccoli-like" or "coastline-like" irregular.
  • Diffuse lymphoma has an indistinguishable border from non-lymphomatous part of thyroid and otherwise is similar to goiter. Internal echoes are also of exceedingly low intensity.
  • The mixed lymphoma showes multiple, patchy hypoechoic lesions, with enhanced posterior echoes in each lesion.

CT

  • CT findings associated with the diagnosis of primary thyroid lymphoma include solitary nodule, multiple nodules, and diffuse enlargement.[19]
  • A characteristic finding ob CT imaging is "donut sign," observed when the lymphoma completely encircles the trachea.

MRI

  • MRI is useful for defining the extent of extrathyroidal invasion of the primary thyroid lymphoma.[17]

Other Imaging Findings

  • There are no other imaging findings associated with primary thyroid lymphoma.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with primary thyroid lymphoma.

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

  • There are no established measures for the secondary prevention of primary thyroid lymphoma.

References

  1. Skarsgard ED, Connors JM, Robins RE (October 1991). "A current analysis of primary lymphoma of the thyroid". Arch Surg. 126 (10): 1199–203, discussion 1203–4. doi:10.1001/archsurg.1991.01410340037006. PMID 1929820.
  2. 2.0 2.1 2.2 2.3 2.4 Pedersen RK, Pedersen NT (January 1996). "Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study". Histopathology. 28 (1): 25–32. doi:10.1046/j.1365-2559.1996.268311.x. PMID 8838117.
  3. Vardell Noble, Victoria; Ermann, Daniel A; Griffin, Emily K; Silberstein, Peter T (2019). "Primary Thyroid Lymphoma: An Analysis of the National Cancer Database". Cureus. doi:10.7759/cureus.4088. ISSN 2168-8184.
  4. Ansell SM, Grant CS, Habermann TM (June 1999). "Primary thyroid lymphoma". Semin. Oncol. 26 (3): 316–23. PMID 10375088.
  5. Aggarwal, Nidhi; Swerdlow, Steven H; Kelly, Lindsey M; Ogilvie, Jennifer B; Nikiforova, Mariana N; Sathanoori, Malini; Nikiforov, Yuri E (2012). "Thyroid carcinoma-associated genetic mutations also occur in thyroid lymphomas". Modern Pathology. 25 (9): 1203–1211. doi:10.1038/modpathol.2012.73. ISSN 0893-3952.
  6. Dundar, Halit Ziya; Sarkut, Pinar; Kirdak, Turkay; Korun, Nusret (2016). "Primary thyroid lymphoma". Turkish Journal of Surgery. 32 (1): 75–77. doi:10.5152/UCD.2015.2935. ISSN 1300-0705.
  7. Holm LE, Blomgren H, Löwhagen T (March 1985). "Cancer risks in patients with chronic lymphocytic thyroiditis". N. Engl. J. Med. 312 (10): 601–4. doi:10.1056/NEJM198503073121001. PMID 3838363.
  8. Hyjek E, Isaacson PG (November 1988). "Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis". Hum. Pathol. 19 (11): 1315–26. doi:10.1016/s0046-8177(88)80287-9. PMID 3141260.
  9. "Exit Disclaimer - US Preventive Services Task Force".
  10. . doi:10.1046/j.1365-2559.1996.268311.x. Check |doi= value (help). Missing or empty |title= (help)
  11. Holm, Lars-Erik; Blomgren, Henric; Löwhagen, Torsten (1985). "Cancer Risks in Patients with Chronic Lymphocytic Thyroiditis". New England Journal of Medicine. 312 (10): 601–604. doi:10.1056/NEJM198503073121001. ISSN 0028-4793.
  12. Hedhili, F.; Kedous, S.; Jbali, S.; Attia, Z.; Dhambri, S.; Touati, S.; Chebbi, A. Goucha; El May, A.; Gritli, S. (2015). "Primary thyroid lymphoma: Case report and review of the literature". Egyptian Journal of Ear, Nose, Throat and Allied Sciences. 16 (2): 171–173. doi:10.1016/j.ejenta.2015.05.002. ISSN 2090-0740.
  13. {{cite book | last = Edge | first = Stephen | title = AJCC cancer staging manual | publisher = Springer | location = New York | year = 2010 | isbn = 978-0-387-88440-0 }
  14. Katna, Rakesh; Shet, Tanuja; Sengar, Manju; Menon, Hari; Laskar, Siddharth; Prabhash, Kumar; D'Cruz, Anil; Nair, Reena (2013). "Clinicopathologic study and outcome analysis of thyroid lymphomas: Experience from a tertiary cancer center". Head & Neck. 35 (2): 165–171. doi:10.1002/hed.22928. ISSN 1043-3074.
  15. Logue JP, Hale RJ, Stewart AL, Duthie MB, Banerjee SS (1992). "Primary malignant lymphoma of the thyroid: a clinicopathological analysis". Int. J. Radiat. Oncol. Biol. Phys. 22 (5): 929–33. doi:10.1016/0360-3016(92)90790-o. PMID 1555984.
  16. Tupchong L, Hughes F, Harmer CL (October 1986). "Primary lymphoma of the thyroid: clinical features, prognostic factors, and results of treatment". Int. J. Radiat. Oncol. Biol. Phys. 12 (10): 1813–21. doi:10.1016/0360-3016(86)90324-x. PMID 3759532.
  17. 17.0 17.1 Takashima S, Nomura N, Noguchi Y, Matsuzuka F, Inoue T (1995). "Primary thyroid lymphoma: evaluation with US, CT, and MRI". J Comput Assist Tomogr. 19 (2): 282–8. PMID 7890856.
  18. Ota H, Ito Y, Matsuzuka F, Kuma S, Fukata S, Morita S, Kobayashi K, Nakamura Y, Kakudo K, Amino N, Miyauchi A (October 2006). "Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid". Thyroid. 16 (10): 983–7. doi:10.1089/thy.2006.16.983. PMID 17042683.
  19. Kim HC, Han MH, Kim KH, Jae HJ, Lee SH, Kim SS, Kim KH, Chang KH (June 2003). "Primary thyroid lymphoma: CT findings". Eur J Radiol. 46 (3): 233–9. doi:10.1016/s0720-048x(02)00134-1. PMID 12758117.
  20. Cha H, Kim JW, Suh CO, Kim JS, Cheong JW, Lee J, Keum KC, Lee CG, Cho J (December 2013). "Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study". Radiat Oncol J. 31 (4): 177–84. doi:10.3857/roj.2013.31.4.177. PMC 3912230. PMID 24501704.
  21. Peixoto, Rita; Correia Pinto, João; Soares, Virgínia; Koch, Pedro; Taveira Gomes, António (2017). "Primary thyroid lymphoma: A case report and review of the literature". Annals of Medicine and Surgery. 13: 29–33. doi:10.1016/j.amsu.2016.12.023. ISSN 2049-0801.

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