thyroid cancer is the most common endocrine malignancy , it accounts for less than 1% of all cancers , and the tumors usually progress slowly .
it makes up 80% of all thyroid cancers . despite high survival rates , local recurrence and metastasis
occur in some patients and this may require more aggressive surgical treatment . it is more common in women ; the incidence varies according to different reports .
male  :  female ratio varies from 1  :  2 to 1  :  10 .
they often appear in the third and fifth decades of life [ 3 , 4 ] .
follicular variant of papillary thyroid cancer subtypes is characterized by follicles lined by cells with nuclear features of papillary carcinoma .
macrofollicular variant of papillary carcinoma ( mvpc ) is a rare subtype of follicle variant , and it was first defined by albores - saavedra et al . in 1991   and was described as encapsulated follicular variant that includes more than 50% macrofollicular in each section .
macrofollicle was defined as a follicle that is of a diameter greater than 250  m . in this study ,
the aim was to examine the prognostic features of mvpc by analyzing the follow - up results of 5 patients diagnosed with mvpc .
demographic data , preoperative data , postoperative treatment methods ( hormone replacement , radioactive iodine ablation therapy ) , locoregional recurrence rates , and prognostic factors of patients who underwent surgery due to thyroid cancer in ege university hospital , department of general surgery , division of endocrine surgery , and were diagnosed with mvpc between january 2000 and january 2006 were retrospectively analyzed .
all treatment decisions were taken by an endocrine council consisting of general surgeons , endocrinologists , nuclear medicine specialists , pathologists , and radiologists , by adopting a multidisciplinary approach . in our clinic , we applied total thyroidectomy for patients diagnosed with thyroid cancer , in a way that no visible tissue would be left behind .
locoregional recurrence was described as cases having pathological lymph nodes on ultrasonography and/or cytology and/or a new determination of a previously nonexisting tissue or presence of increased levels of thyroglobulin .
the mean age of the patients included in the study was 41 ( 3848 ) .
four of them were females ( 80% ) and 1 was male ( 20% ) .
while the reason for one patient 's admission was symptoms of hyperthyroidism , no symptoms were detected in other patients . on physical examination , one of the patients had palpable thyroid nodules on right upper lobe , and another had bilateral palpable nodules .
all patients underwent a total thyroidectomy . in the histological examination of tumors that were observed in thyroidectomy materials ,
these cells lining the follicles were of clear nuclei and showed obvious deformity of the nuclear membrane , notch structure , and sparse pseudoinclusion .
also , vacuolization was spotted in colloid in the periphery of the follicle structures . with these histological findings
, the tumor found in all patients was reported to be mvpc ( figures 1 and 2 ) .
more than 50% of the cross - sectional area of the tumor was composed of macrofollicles ( follicles 250  m in diameter ) in all patients .
pathological tumor sizes were reported as < 1  cm in 2 patients , 1.12  cm in another two , and 2.13  cm in the last one .
multifocal tumors were reported in one patient . there was no tumor invasion ( soft tissue , capsules , and vessels ) in any of the patients . upon detecting lymph nodes in intraoperative macroscopic pathology , one patient ( 20% )
was applied ipsilateral central ( 6th level ) lymph node dissection and 4 metastatic lymph nodes were reported histologically out of 11 dissected lymph nodes . while four of the patients ( 80% ) were applied radioactive iodine ablation ( ria ) in the postoperative period , 1 ( 20% ) was not .
the patient , who was detected to have lymph node metastases , received ria at a dose of 225  mci , and the other three received < 150  mci .
papillary thyroid carcinoma is the most common malignant tumor of the thyroid gland , and it is in the group of well - differentiated tumors thanks to good prognosis .
mvpc histologically consists of follicles and cells of papillary cancer nuclear characteristics which line these follicles .
while macrofollicles can also be encountered in classical papillary cancer and follicular variant , more than 50% of the tumor in macrofollicular variant consists of macrofollicles .
defining this variant is important as it can easily be mistaken with benign thyroid lesions , such as nodular goiter and follicular adenoma .
macrofollicles in mvpc are lined by tumor cells with nuclei that are large , overlapping , clear , and notched and that sometimes have cores containing pseudoinclusion .
minor nuclear irregularities can also be seen in benign lesions , but this histological finding is not enough for a cancer diagnosis alone .
in addition , unlike benign thyroid lesions , there is a remarkable nuclear deformity in the shapes of cells .
histological diagnosis is made according to nuclear properties of tumor cells paving the macrofollicles because macrofollicles are lined by squamous cells in some mvpcs .
definitions as case presentations exist in the literature , the largest series of which is the one made by albores - saavedra et al . in 1991 with 29 patients to define mvpc and republished the results in 1997 with the adding up new cases .
there are no large series of patients , but it can be said that it is more common in females than males .
mvpc was reported to have a very good prognosis with its lower rate of lymph node metastasis compared to classical papillary cancer [ 9 , 10 ] .
clinically , they are usually included in nonaggressive tumors , and in the study of albores - saavedra et al .
rate of lymph node metastasis was reported as 11.8% , in their second study as 20.6% , and in another study by evans as 7.1% ( 1 metastasis in 14 patients ) [ 6 , 9 , 11 ] . in this study ,
mvpc lymph node metastases rate 's being lower while it is higher in general papillary cancer is associated with the fact that it is a well - limited capsulated and having low proliferative activity [ 6 , 9 ] .
contrary to the abovementioned good prognostic data , 2 out of 29 patients were reported to have capsular invasion , vascular invasion , and lung metastasis in the study of albores - saavedra et al . .
2 cases with aggressive behaviour ( extrathyroid extension , lymph nodes , and bone and lung metastases ) were reported . in this study ,
distant metastasis and death were not detected in a mean follow - up period of 7.2 years , and locoregional recurrence rate was observed to be high ( 60% ) . in a study we conducted in our clinic but not yet published , 5 out of 181 patients ( 2.7% ) diagnosed with well - differentiated thyroid cancer were detected to have mvpc . in a mean follow - up period of 7.1 years , locoregional recurrence rate of 181 patients was determined to be 22.6% ( 41 patients ) , and the locoregional recurrence rate of mvpc group in this group of patients was found to be higher ( 60% ) . in this small series , we describe two cases of microcarcinoma exhibiting macrofollicular architecture : these are two aspects generally correlated with an excellent prognosis . regarding the clinical behavior of these cases in this series , one of the recurrent patients had a microcarcinoma .
this patient , as well as the rest in this series , had no invasion reported on histopathological review .
although mvpc is said to be a variant that has a perfect prognosis and less rate of lymph node metastasis than those of classical papillary cancer , in this study the rate of lymph node metastasis was found to be 20% and locoregional recurrence rate 60% .
it can be argued that the number of patients included is not enough to make definite statements about prognosis , but studies including such large groups do not exist in the literature .
special care should be given especially because one can encounter other benign thyroid diseases in fine - needle aspiration biopsy and histological evaluation .
as its histological subtypes and the clinical behaviour of these subtypes are highly variable , this definition has started to prove insufficient though papillary cancer is one of the diseases with best prognosis .
for this reason , we are of the opinion that prospective prognostic studies that evaluate all papillary cancer subtypes together with higher number of patients are a need today .
 
 objective . 
 the main aim of this study was to comparatively analyze the recurrence and prognosis of this rare variant with the literature by analyzing the follow - up data of 5 patients diagnosed with papillary cancer macrofollicular variant . 
 methods . 
 the demographic data , radiological and pathological data , and prognostic data of 5 patients who underwent surgery for thyroid cancer and were diagnosed with papillary cancer macrofollicular variant pathologically were retrospectively analyzed . 
 results . the mean age of patients whose mean follow - up 
 period was determined as 7.2 years was 41 , and the male / female ratio was 4/1 . 
 all patients underwent total thyroidectomy . 
 the pathology report of 2 patients ( 40% ) revealed macrofollicular variant of papillary microcancer , and 3 patients papillary cancer macrofollicular variant . 
 central dissection was performed in one patient ( 20% ) due to macroscopic pathologic lymph node and 4 metastatic lymph nodes were reported . also 
 , locoregional recurrence was present in 3 out of 5 patients ( 60% ) . conclusions . 
 although an impression of earlier and increased risk of recurrence in papillary carcinoma with macrofollicular variant has been documented , more studies with extensive follow - up times and large populations are required . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion