Thyroid Lymphoma non-Hodgkin

7/21/2019 Thyroid Lymphoma non-Hodgkin

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Primary thyroid lymphoma can be defined as a lymphoma that arises from the thyroid gland.

This definition excludes those that invade the thyroid gland as a consequence of either metastasis

or direct extension. Primary thyroid lymphomas are practically always non-Hodgkin lymphomas(H!s". Primary thyroid Hodgkin disease is extremely rare.

H!s can be divided into aggressive and indolent cell types. #ggressive H!s comprise a large

number of cell types$ the most common of which is large-cell lymphoma. They most frequently

arise from lymph nodes$ but an extranodal site can be the primary source in approximately %&'of cases$ and the thyroid gland is among the most common of these extranodal sites.

Thyroid H! represents approximately .) to .*' of all H!s.+, t is highly curable$ without

the need for extensive surgery. #ccordingly$ early recognition and correct treatment of this

condition is vital. The most common cell type is diffuse large-cell lymphoma$ either associatedor unassociated with mucosa-associated lymphoid tissue (#!T" lymphoma (#!Toma". The

best treatment results for primary thyroid large-cell lymphoma are with combined-modality

therapy/ for primary thyroid #!Toma$ radiation therapy alone is probably adequate.

+),

Pathophysiology

Thyroid lymphomas are very frequently associated with Hashimoto thyroiditis (HT". 0onversely$

there is a markedly increased incidence of primary thyroid lymphomas in patients with HT.+%,

1uch lesions are an aggressive or high-grade variant$ whereas a low-grade #!T is an indolenttype.

!ike other low-grade #!Tomas$ such as those presenting in the parotid in association with

123gren syndrome$ those arising in the thyroid also occur in association with an autoimmune

disorder (in this case$ HT". The hypothesis is that chronic antigenic stimulation secondary to theautoimmune disorder leads to chronic proliferation of lymphoid tissue$ which eventually

undergoes a mutation that leads to the development of lymphoma.

Epidemiology and Prognosis

Primary thyroid lymphoma is rare$ constituting only -)' of all extranodal lymphomas andapproximately )-4' of all thyroid malignancies.+5$ %$ 6$ 7, #s with other non-Hodgkin lymphomas$

the median age of presentation in patients with thyroid lymphoma is usually close to 6& years. +7$ 6,

ost cases occur in women.

The prognosis for patients with thyroid large-cell lymphoma usually is favorable because theytypically present with locali8ed disease$ which is amenable to treatment with chemotherapy and

radiation. The cure rate is typically high (see Treatment". # large population-based study that

evaluated prognostic factors found that older age$ advanced stage$ histologic subtype$ and lack of radiation9surgical treatment were adverse factors for survival.+*,

History and Physical Examination



The most common clinical presentation of a thyroid lymphoma is that of a rapidly enlarging

thyroid mass$ frequently in association with neck adenopathy. 0ompressive symptoms may be

present. n most cases the patient is a woman$ often with a history of Hashimoto thyroiditis.

Diferential Diagnoses

• #naplastic Thyroid 0arcinoma

• edullary Thyroid 0arcinoma

• Papillary Thyroid 0arcinoma

• Thyroid odule

Laboratory Studies

:nce the diagnosis of thyroid non-Hodgkin lymphoma (H!" is established$ the following

laboratory studies should be obtained;

• 0omplete blood count (0<0"

• 1erum lactate dehydrogenase (!=H" level

• 1erum beta ) -microglobulin level

• <one marrow aspiration and biopsy

• Thyroid function tests

• #ntithyroglobulin or antimicrosomal antibodies

The serum !=H and beta) -microglobulin levels are important because of their ability to help

predict the prognosis.+4, The 0<0 and the bone marrow studies are important as part of thestaging evaluation. <ecause of the high incidence of hypothyroidism$ it is important to evaluate

thyroid function.

Plain Radiography, CT, Gallium Scanning, and PETt is necessary to perform chest radiography and computed tomography (0T" of the head andneck$ the chest$ the abdomen$ and the pelvis. (1ee the image below." These are critical tests for

determining the stage or extent of disease.

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>apidly enlarging thyroid mass

occurring in association with neck adenopathy.

n cases involving bulky disease$ either gallium scanning or positron emission tomography(P?T" should be performed. These modalities can be helpful later on in determining whether any

residual abnormality seen on radiographic studies after treatment contains active lymphoma or

2ust scar tissue.

Histologic Findingsn current practice$ the diagnosis of thyroid lymphoma can be easily established by means of

either fine-needle aspiration (@#" or core-needle biopsy$+4, thus obviating the extensive surgery

usually performed for thyroid carcinoma. Aith the aid of immunophenotyping$ non-Hodgkin

lymphoma (H!" should be readily distinguishable from thyroid carcinoma. @urthermore$ thedistinction between large-cell lymphoma and follicular center-cell lymphoma can be made on the

basis of cytologic and immunophenotyping criteria.

The ma2or histologic types of thyroid H! are as follows+B, ;

•!arge-cell lymphoma

• @ollicular lymphoma

• ucosa-associated lymphoid tissue (#!T" lymphoma (#!Toma"

• <urkitt lymphoma (rare"



n a study from Capan that evaluated * patients with primary thyroid lymphoma$ the

distribution of pathologic diagnoses was as follows+&, ;

• =iffuse large <-cell lymphoma (=!<0!" - 5%'

• =!<0! with #!Toma - 4'

• #!Toma - 5*'

• :ther - )'

Staging

=etermining the extent of disease in H! is crucial for helping determine the prognosis and

select treatment. n thyroid lymphoma$ however$ a conceptual problem arises$ in that most

investigators have tended to believe that only thyroid lymphomas that are in the early #nn #rborstages (ie$ -" can be considered as being of primary thyroid origin.

The explanation for this view is that advanced presentations can represent a lymphoma

metastasi8ing to the thyroid rather than a primary thyroid lymphoma. #lthough primary thyroid

lymphomas have metastatic potential and can present in stages -D$ there is no histologicmarker that can be used to separate those that are primary in the thyroid from those that are

metastatic to the thyroid/ thus$ most literature series$ by definition$ include only stage - cases.

@or the purposes of prognosis$ the aggressive thyroid cell types (most commonly the large-cell

H!s" can be classified on the basis of the nternational Prognostic ndex (P".+, This

prognostic system assigns point to each of the following variables;

• #ge older than 6& years

• Performance status greater than

• ?levated lactic dehydrogenase (!=H" level

• umber of extranodal sites greater than

• #nn #rbor stage -D

n a study by Ha et al that tested the ability of the P to predict the prognosis for patients with

thyroid lymphoma$ the 7-year survival rate was 46' for those presenting with an P of &$

compared with 7&' for those with an P greater than &. +B, . These data included patients treatedwith radiation therapy alone$ patients treated with chemotherapy alone$ and patients treated with

combined-modality therapy. # )&& study evaluated prognostic factors in a large population-

based study and found that older age$ advanced stage$ histologic subtype$ and lack ofradiation9surgical treatment were adverse factors for survival.+*,



Chemotherapy and Radiation Therapy

Large-cell lymphoma

The management of thyroid lymphoma does not differ significantly from that of any other

lymphoma presenting in a nodal site. =ata suggest that the best results are obtained with

combined-modality therapy that includes the 0H:P (cyclophosphamide$ doxorubicin$

vincristine$ prednisone" regimen and radiation therapy. #s many as B&' of cases are failure-free

after this approach.+), The number of courses of chemotherapy administered can be limited to

three for patients with locali8ed stage -$ especially those with good prognostic features (ie$ an

nternational Prognostic ndex +P, of & and tumor less than 7 cm in diameter".

>adiation therapy is used to consolidate the response to 0H:P for those receiving only three

courses. 0urrently$ rituximab is given as part of the 0H:P regimen (>-0H:P". However$

patients with an P greater than should be managed with six courses of >-0H:P$ based on the

results discussed below.

n the !H-B4.7 study$ conducted in %BB patients 6&-4& years of age with diffuse large <-celllymphoma$ &-year progression-free survival was %6.7' with >-0H:P$ versus )&' for 0H:P

alone$ and &-year overall survival rates were 5%.7' versus )*.6'.+%, The results can be applied

to primary thyroid lymphoma. #lthough the study did not include patients younger than 6& years$

another study found that such patients have also benefitted from rituximab. +5,

>adiation therapy is most commonly delivered after three to six courses of >-0H:P

chemotherapy. The radiation fields most commonly used are either involved field or modified

mantle$ which includes the thyroid$ the bilateral neck and supraclavicular region$ and the

mediastinum.+7,

Long-Term Monitoring

@ollow-up care for patients with thyroid lymphoma is similar to that for patients with any other

lymphoma. n brief$ patients should be seen approximately every % months during the first year

and every 5 months during the second year. #fter the second year$ the risk of relapse diminishes

substantially for patients with tumors of the large-cell (ie$ aggressive" types.

n contrast$ the risk of recurrence for the low-grade (ie$ indolent" lymphoma types does not

decline as sharply after ) years of observation. #fter % years of follow-up$ the probability of cure

in a patient with diffuse large-cell lymphoma is greater than B&'.

Medication Summary

Treatment for large-cell lymphoma is selected on the basis of prognostic factors. ost

investigators treat patients whose nternational Prognostic ndex (P" result is favorable by using

the standard 0H:P (cyclophosphamide$ doxorubicin$ vincristine$ prednisone" regimen$ followed

by irradiation consolidation in patients with #nn #rbor stages -. Three to six courses of

chemotherapy are administered.



Patients who present with #nn #rbor stage and an P of & with tumor diameters smaller than 7

cm could be treated with three courses of 0H:P followed by local irradiation. The role of

rituximab in patients with these favorable presentations has not been explored$ but most

clinicians include it in the treatment regimen. #ll other patients receive six courses of 0H:P and

radiotherapy. 0onsider investigational regimens in patients with P scores greater than &.

n general$ the addition of rituximab provides benefit in survival and disease-free survival rates$

and the results are also assumed to apply to primary thyroid large-cell lymphomas.

ntineoplastic gents

Class Summary

#ntineoplastic agents inhibit cell growth and proliferation.

!ie" #ull drug in#ormation

Cyclophosphamide

0yclophosphamide is chemically related to nitrogen mustards. t is an alkylating agent/ the

mechanism of action of active metabolites may involve cross-linking of =#$ which may

interfere with growth of normal and neoplastic cells.


Doxoru$icin %driamycin&

=oxorubicin intercalates =# and inhibits topoisomerase / it produces free radicals that may

cause destruction of =# and inhibit growth of neoplastic cells.


!incristine %!incasar !'S&

DincristineEs mechanism of action is uncertain/ it may involve a decrease in reticuloendothelial

cell function or an increase in platelet production.

ntineoplastics( Monoclonal nti$ody

Class Summary

onoclonal antibodies are genetically engineered chimeric murine-human immunoglobulins

directed against proteins involved in cell cycle initiation.


Rituxima$ %Rituxan&

>ituximab is a genetically engineered chimeric murine9human monoclonal antibody

(immunoglobulin F +gF, kappa" against 0=)& antigen on the surface of normal and

malignant < cells. t is not to be administered as an intravenous bolus.

Corticosteroids

http://reference.medscape.com/drug/cytoxan-cyclophosphamide-342214


http://reference.medscape.com/drug/doxorubicin-342120


http://reference.medscape.com/drug/oncovin-vincasar-pfs-vincristine-342097


http://reference.medscape.com/drug/rituxan-rituximab-342243












Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects.

0orticosteroids modify the bodyEs immune response to diverse stimuli.


Prednisone

Prednisone is an immunosuppressant used for treatment of autoimmune disorders. t may

decrease inflammation by reversing increased capillary permeability and suppressing

polymorphonuclear leukocyte (P" activity.


Prednisolone %Millipred( Pediapred&

Prednisone is useful for treating inflammatory and allergic reactions/ it may decrease

inflammation by reversing increased capillary permeability and suppressing polymorphonuclear

leukocyte (P" activity. t decreases autoimmune reactions$ possibly by suppressing key

components of immune system.

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