更支持PTC,Warthin-like variant

桥本氏病

 桥本氏病

 图5是CK19,

图6是TPO,

图8是CK5/6,

图9是P63.

 Warthins 瘤鳞化

  桥本

  非常好的病例！建议版主顶置，并讨论！！

非常想向Warthin瘤样乳头状癌上靠，而且结构上很像乳头状癌，但没有诊断经验！

ABSTRACT：Warthin-like tumor of the thyroid is a recently described rare variant 

of thyroid papillary carcinoma. h  e distinguishing histological feature 

of this variant is papillary foldings lined by oncocytic neoplastic cells 

with clear nuclei and nuclear pseudoinclusions, accompanied by 

prominent lymphocytic infiltrate in the papillary stalks. Its prognosis 

has been reported to be almost similar to conventional papillary 

carcinoma. In this case series, we report four cases with Warthin-like 

papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul 

University Faculty of Medicine Department of Pathology in 2008 and 

2009. h  ree patients were female. h  e mean patient age was 39 years 

(range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). 

All of the cases had lymphocytic thyroiditis in the background. None 

of the tumors showed lymphovascular invasion. h  e patients are free 

of any recurrence and/or distant metastasis with a mean follow-up 

of 25 months. h  is rare variant of thyroid papillary carcinoma with 

distinct histopathological features should be indicated in pathology 

reports. Further studies and long-term follow-up of patients are 

needed to highlight the biological behavior of this variant. 

 TheWarthin-like variant of papillary thyroid carcinoma was

first described in 1995 by Apel et al. [2] and represents a

rare variant of PTC, with approximately eighty cases having

been reported in literature to date [1]. Apel et al. chose

the name “Warthin-like tumor” because of its histological

resemblance to papillary cystoadenoma lymphomatosum or

Warthin tumor of the salivary glands.

Patients affected by WaLPTT have similar demographic

and clinical characteristics to those affected by PTC. Table 1

shows these characteristics, as reported in the most consis-

tent series published to date, excluding case reports [2–7].

WaLPTT typically arises at an earlier age, as compared to

PTC, and there is also a stronger predominance of females.

Among the 54 patients reviewed, the mean age was 50

years and there were only five males (9%). The clinical

presentation is the same as that for other differentiated

thyroid tumors: absence of signs and symptoms when the

lesions are single, small, and deep; palpablemasses, glandular

swelling, and swallowing and/or phonatory alterations for

larger, superficial, and/or multiple lesions. Signs, symptoms,

and alterations in thyroid function related to thyroiditis or

goitre may be also present. Furthermore, features of US and

CT imaging of WaLPTT are identical to those for PTC. As

a consequence, diagnosis of WaLPTT cannot be based on

clinical and imaging data alone.

FNA may be useful in this regard, but its role in the

diagnosis ofWaLPTT is not yet clear. Generally, it is possible

to appreciate the presence of groups of follicular cells and

papillary fragments against a background of lymphocytes

and plasma cells, which infiltrate the fibrovascular cores.

Oncocytic cells are often admixed with lymphocytes. The

nuclear characteristics of tumoral cells are generally those

of PTC (nuclear chromatin clearing, membrane thickening,

grooves, and pseudoinclusions) and oncocytes (round nuclei

with coarse chromatin and prominent nucleoli) [5]. Such

patterns suggest PTC or lymphocytic thyroiditis, or both.

Indeed, these were the most frequent diagnoses in the

literature on patients affected byWaLPTT. Baloch and LiVolsi

report data on seven FNAs; there were four diagnoses of

PTC, two of lymphocytic thyroiditis and one of atypical

cells [5]. In the series of D’Antonio et al., all patients

underwent FNA and two of them had a diagnosis of PTC;

in one case, the results of FNA were inconclusive [4]. In

our case and those of Amico et al., Sarkady et al., and

Lam et al., the preoperative diagnosis based on FNA was

PTC or thyroiditis [1, 8, 9].FNAisprobablymoreusefulfor

the evaluation of cervical lymph node involvement, as in our 

case, and for planning the appropriate surgical strategy and

multidisciplinary management.

The macroscopic appearance of WaLPTT is generally

that of a white-greyish, well circumscribed nodule, unen-

capsulated and confined to the thyroid gland. It may contain

cystic and/or haemorrhagic areas. Its mean size among the

54 reviewed patients was 1.5 cm (range 0.3 to 5 cm). To

our knowledge, only one paper has reported a WaLPTT

larger then 5 cm [1]. The color of the remaining thyroid

parenchyma generally ranges from red brownish to tan and a

variable number of nodules of different sizes may be present.

The histological diagnosis of WaLPTT is based on the

evidence of a morphological pattern featuring papillae lined

by oncocytic cells admixed with lymphocytes and sparse

plasma cells. The distinctive feature is the lymphocytic infil-

tration of the stalks of the papillae. Furthermore, it is possible

to observe cysts or a small number of tall cells. Vascular

and capsular invasions are rare. Differential diagnosis must

be conducted with other variants of papillary cancer with

similar morphology, such as Hurthle cell carcinoma (HCC)

and tall cell carcinoma (TCC). The former usually lacks

lymphoplasmacytic infiltrates and is rarely associated with

lymphocytic thyroiditis [2, 5]; the latter is characterized

by a papillary structure with elongated oncocytes, with a

height that is more than twice their width, and by neoplastic

aggressiveness with more frequent vascular, capsular, and

nodal invasion [10].

Theroleofimmunohistochemistryindifferential diag-

nosis with Hurthle cell and tall cell carcinomas is limited.

Indeed, in our case it was not necessary for diagnosis as

the morphological pattern was clear. Intense staining for the

following markers has been reported in literature: galectin-3,

HBME-1, CK19, TTF-1, thyroglobulin, EMA, AE1/AE3,

S-100 protein, cyclin D1 and UCHL1, CD3+, CD20+,

and CD79+ (for the lymphocytic population). Ostrowski

and Merino believe that CD15 immunostaining represents

a distinctive characteristic of tall cell carcinomas and a

predictive factor for advanced stage or poor prognosis [11].

Nevertheless, this marker was also found in WaLPTT, which

has a better prognosis than TCC.

The neoplastic behaviour of WaLPTT seems to be similar

or even better than that of classical PTC. Vera-Sempere et al.

hypothesized that it is a hybrid of TCC and HCC and

some immunohistochemical evidence supports this theory

[12]. Short- and long-term prognosis seems to be excellent.

Lam et al. describe a case of a 74-year-old Chinese woman

affected by WaLPTT with dedifferentiated (anaplastic) area

[9]. She had a 3.5 cm PTC of the right lobe with ipsilateral

recurrent laryngeal nerve involvement; a supraclavicular

lymph node was shown by FNA to be metastatic. The patient

refused any treatment for three years, but agreed to undergo

surgery when her condition worsened. She underwent pal-

liative surgery and died 15 months later. This case seems to

have involved the natural evolution of an advanced anaplastic

thyroid carcinoma (with areas of WaLPTT) that remained

untreated for a long time, rather than a typical WaLPTT.

Elsewhere, Amico et al. reported a case of a 6 cm WaLPTT

with less than 5% of the tumor area being occupied by

anaplastic tissue in a 79-year-old woman with laterocervical

lymph node metastasis [1]. The patient promptly underwent

surgery and was alive without evidence of disease 23 months

later. It is probable that in such situations the anaplastic

component, even when it represents a small percentage of

the overall tumor area, dictates the prognosis, which may be

poor when appropriate treatment is not provided.

Other cases of cervical nodal metastasis have been

reported in literature, but such events are generally rare

[3, 8]. Among the 54 cases reviewed here, only 12 (22%) had

lymph node metastasis, which represents an incidence lower

than that for traditional PTC. Prognosis was favourable in

almost all cases, but follow-up times were generally short,

with only a few cases being followed for more than 3 years.

The most reliable explanation for the low rates of nodal

involvement and favourable prognosis in WaLPTT is the

presence of lymphatic tissue within the tumor, which seems

to contrast and restrain neoplastic progression and diffusion.

The therapeutic management of patients with WaLPTT

is similar to that of patients with PTC and depends

substantially on the disease stage and the presence of neg-

ative prognostic factors such as familiarity, history of neck

irradiation, and syndromic endocrine disease. The diagnosis

of WaLPTT is histopathological and generally based on

surgical specimens. This means that the therapeutic plan

for patients with WaLPTT must be assessed after surgery.

The reports reviewed in this paper are mostly pathological

and lack detailed data on postoperative treatments such as

radioiodine ablation and follow-up modalities. As the bio-

logical behaviour of WaLPTT is comparable to that of PTC,

postoperative management should also be identical. Further

surgery for completion of thyroidectomy or lymphadenec-

tomy, radioiodine ablation, and other treatments may be

employed in high-risk patients. Our patient underwent

postoperative radioiodine therapy due to evidence of residual

thyroid tissue and capsular invasion and is undergoing the

same postoperative follow-up and treatment program used

in patients with classic PTC.

4. Conclusions

Warthin-like papillary thyroid carcinoma is a recently

described variant of papillary thyroid cancer that is fre-

quently associated with lymphocytic thyroiditis.Morpholog-

ically, it resembles Warthin tumors of the salivary glands,

with T and B lymphocytes infiltrating the stalks of papillae

lined with oncocytic cells. Diagnosis is histopathological and

based on morphology rather than immunohistochemistry.

Surgical and postoperative management is identical to that

of classic differentiated thyroid cancer, while prognosis seems

to be favourable. Larger prospective long-term studies are

necessary to better understand the biological behaviour of

such tumors and their clinical and prognostic impact.