
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39029040
MD-D-24-03321
00042
10.1097/MD.0000000000038952
3
4300
Research Article
Observational Study
Tumor deposits in thyroid carcinomas
https://orcid.org/0000-0003-3516-952X
Guray Durak Merih MD a*
Gokcay Deniz MD denizgkcy@gmail.com
a
Emecen Serra Begum MD serrabegumemecen@gmail.com
a
Ozdogan Ozhan MD ozhan.ozdogan@deu.edu.tr
b
Sevinc Ali Ibrahim MD ibrahim.sevinc@deu.edu.tr
c
Ikiz Ahmet Omer MD ahmet.ikiz@yahoo.com
d
Dogan Ersoy MD, PhD drersoydogan@gmail.com
d
Karabay Nuri MD nuri.karabay@deu.edu.tr
e
Ellidokuz Hulya MD hulya.ellidokuz@deu.edu.tr
f
Sarioglu Sulen MD sulensari@gmail.com
a
a Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
b Department of Nuclear Medicine, Dokuz Eylul University School of Medicine, Izmir, Turkey
c Department of General Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey
d Department of Ear, Nose, Throat and Head & Neck Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey
e Department of Radiology, Dokuz Eylul University School of Medicine, Izmir, Turkey
f Department of Preventive Oncology, Dokuz Eylul University Institute of Oncology, Izmir, Turkey
* Correspondence: Merih Guray Durak, Department of Pathology, Dokuz Eylul University Faculty of Medicine, Inciralti, Izmir 35330, Turkey (e-mail: merih.guray@deu.edu.tr).
19 7 2024
19 7 2024
103 29 e3895228 3 2024
20 6 2024
25 6 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4–341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.

medullary carcinoma
papillary carcinoma
thyroid
tumor deposits
OPEN-ACCESSTRUE
==== Body
pmc1. Introduction

Tumor deposits (TDs) are discontinuous neoplastic masses from the primary tumor at the lymphatic draining area. This term has been designated as various names in the literature, including tumor nodule, extranodal focus, tumor aggregate, discontinuous carcinoma, or extranodal cancer deposit.[1] Although first reported in 1935, the interest in TDs arose particularly in the last 3 decades, with increasing literature about its association with poor prognosis in different cancer groups.[2–9] Most studies regarding the prognostic significance of TDs are in colorectal carcinomas,[2,10–13] accordingly, in the recent American Joint Committee on Cancer classification system their presence change the nodal status to pN1c, if no metastatic regional lymph nodes are detected on pathological examination.[14]

Thyroid carcinomas, particularly differentiated thyroid carcinomas arising from the follicular epithelial cells, are the most common endocrine malignancies.[15] Thyroid papillary carcinoma (TPC), by far, constitutes most of the differentiated carcinomas. TPCs are mainly biologically indolent tumors with excellent prognosis, and local recurrence or distant metastasis have been detected only in a minority of cases.[15–18] Many well-known prognostic factors of these tumors have been identified, including the patient age at diagnosis, male sex, tumor size, tumor cell type and/or tumor growth pattern, nodal metastasis, incomplete surgical excision, extrathyroidal extension, and distant metastasis.[16] Nevertheless, since detection and diagnosis of these tumors have increased in the past 20 to 30 years, major concern regarding overtreatment vs undertreatment of the patients have evolved,[16] and determining prognostic and predictive markers for appropriate treatment planning will have a positive impact on tumor control as well as life quality of patients.

Thyroid medullary carcinoma (TMC), on the other hand, is a malignant tumor of the thyroid gland derived from parafollicular C cells, and it constitutes < 2–3% of all thyroid malignancies.[16,19] Although relatively rare, it is an aggressive neoplasm with higher rate of both locoregional recurrence and distant metastases, compared to TPC. Angioinvasion is a marker of aggressive behavior in these tumors.[20] In addition, increased mitotic figures and Ki-67 proliferation index, and/or presence of tumor necrosis, that define high grade TMC according to the recent World Health Organization classification of endocrine neoplasms are significant prognostic markers.[16]

In this study, we aimed to investigate the incidence of TDs in our thyroid carcinoma case series, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their presence.

2. Methods

This study was approved by Dokuz Eylul University Ethics Committee (7686-GOA). A total of 198 patients with thyroid carcinoma diagnosis, who had cervical lymph node sampling and/or dissection between 2001 and 2019, were selected from the archives of our pathology department. Two cases with diagnosis of follicular carcinoma and poorly differentiated carcinoma, and 2 cases in which the presence of TDs could not be evaluated due to missing blocks/slides, were excluded from the study population for statistical relevance. The lymph node slides of 194 patients obtained from the department of pathology archives were re-reviewed by 2 pathologists (DG, SBE). Subsequently, all slides with TDs were evaluated by 2 endocrine pathologists with experience in TDs (MGD, SS), in order to provide consensus.

Any tumor mass in the adipose tissue devoid of lymph node architecture, either with regular or irregular contours, was identified as a TD[9,21] (Figs. 1 and 2). In case of necessity, endothelial markers were performed to exclude intravascular tumor emboli. Tumor masses either with adjacent peripheral nerve, blood vessel and/or lymph vessel in vicinity or not, were taken into consideration for TDs.

Figure 1. Tumor deposit with regular contours (H&E, X60). The tumor mass is surrounded by a fibrous capsule, but devoid of lymph node structures. Endothelial markers were performed in this case, in order to exclude intravascular tumor embolus.

Figure 2. Tumor deposit with irregular contours, adjacent to vascular structures (H&E, X100).

The clinicopathologic features of the patients, including age at diagnosis, sex, histologic type and subtype of the tumor, size of the tumor, multifocality (presence of more than 1 tumor focus in a thyroid lobe), bilaterality (presence of tumor focus in both thyroid lobes), presence of lymphovascular and perineural invasion, status of the surgical margins, presence of intrathyroidal and extrathyroidal extension, total number of lymph nodes, and total number of metastatic lymph nodes were obtained from the medical records/pathology reports of the patients. Pathology slides of the primary surgery specimens were reevaluated for missing parameters in the pathology reports. Follow-up information of the patients was obtained from medical charts and registry records. Locoregional recurrence, either radiological or biochemical, detected by ultrasonography or serum thyroglobulin levels, distant metastasis, date of death or last encounter were recorded.

2.1. Statistical analysis

Statistical analyses were performed using the SPSS statistical software package, version 29.0 (SPSS Inc., Chicago). The patients were grouped according to the presence or absence of TDs. Chi-square, Fisher exact test and Mann–Whitney U test were used to evaluate possible associations between covariates and the clinical outcome. Recurrence free survival (RFS) and overall survival (OS) rates were estimated using the Kaplan–Meier method. The log-rank test was used to compare survivals of different groups. Multivariate analyses were carried out using Cox proportional hazards model. All tests were 2-tailed and P values of <.05 were considered to be statistically significant.

3. Results

The patient series consisted of 129 (66.5%) women and 65 (33.5%) men. The mean age of the patients was 42.8 ± 15.3 years; the median age of the patients was 40.5 years (range, 15–83 years). Neck dissection procedure of the patients were as follows: central compartment dissection in 43 patients (23.9%), central and lateral compartment dissection in 112 patients (62.2%), and lateral neck dissection only in 25 patients (13.9%). In 14 consultation cases, classification of neck dissection could not be verified. One hundred and seventy-six patients (90.7%) had diagnosis of TPC, whereas 18 patients (9.3%) had TMC. TDs were detected in 54 (27.8%) patients. Forty-four patients with TPC (25.0%) and 10 patients with TMC (55.6%) had TDs (P = .006). The most frequent subtypes of TPC were “classical” (79.0%) and “follicular” (16.5%) subtypes. TDs were detected in 35 of 139 (25.2%) “classical” and 8 of 29 (27.6%) “follicular” subtype TPC cases. Most of the TDs (77.8%) were identified in the primary surgery, and most of them (84.6%) were encountered in the central + lateral neck dissection group.

There were 34 patients who had their thyroidectomy procedure performed in other institutions, and had pathology consultation in our department. In 11 to 15 consultation cases, in whom either the paraffin blocks or slides were missing in our pathology archives, parameters such as multifocality, presence of tumor capsule, intrathyroidal and extrathyroidal extension, lymphovascular and perineural invasion as well as status of the surgical margin could not be evaluated thoroughly.

In 93 of 180 patients (51.7%) multifocal tumor was present, whereas in 108 of 180 patients (60.0%) tumor was bilateral. In 74 patients (41.1%) tumor was both multifocal and bilateral. Encapsulation of the tumor, either total or partial, was detected in 86 of 180 patients (47.8%). Extracapsular extension, intrathyroidal extension, and microscopic extrathyroidal extension were identified in 80 of 180 (44.4%), 86 of 181 (47.5%) and 62 of 183 patients (33.9%), respectively.

In univariate analysis, TDs were more frequent in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). However, there was no statistically significant difference for TDs when age at diagnosis (P = .292), intrathyroidal extension (P = .801), vascular invasion (P = .119), perineural invasion (P = .130), status of surgical margins (P = .193), and locoregional recurrence (P = .256) were considered. Clinicopathological features of the cases according to TD positivity are shown in Table 1.

Table 1 Clinicopathological features of the cases according to tumor deposit positivity.

Variables	Tumor deposit	P value	
Negative no. (%)	Positive no. (%)	Total no. (%)	
Age at diagnosis					
 ≥55 years	32 (62.7)	19 (37.3)	51 (26.3)	0.080	
 <55 years	108 (75.5)	35 (24.5)	143 (73.7)	
Sex					
 Men	41 (63.1)	24 (36.9)	65 (33.5)	0.045	
 Women	99 (76.7)	30 (23.3)	129 (66.5)	
Histological type					
 Papillary carcinoma	132 (75.0)	44 (25.0)	176 (90.7)	0.006	
 Medullary carcinoma	8 (44.4)	10 (55.6)	18 (9.3)	
Pathologic T classification					
 pT1a	30 (83.3)	6 (16.7)	36 (19.5)	<0.001	
 pT1b	62 ((81.6)	14 (18.4)	76 (41.1)	
 pT2	28 (65.1)	15 (34.9)	43 (23.3)	
 pT3	14 (51.9)	13 (48.1)	27 (14.6)	
 pT4	0 (0.0)	3 (100.0)	3 (1.6)	
Multifocal tumor					
 Negative	70 (80.5)	17 (19.5)	87 (44.8)	0.017	
 Positive	60 (64.5)	33 (35.5)	93 (47.9)	
Extrathyroidal extension					
 Negative	98 (81.0)	23 (19.0)	121 (62.4)	<0.001	
 Positive	34 (54.8)	28 (45.2)	62 (32.0)	
Intrathyroidal extension					
 Negative	68 (71.6)	27 (28.4)	95 (49.0)	0.801	
 Positive	63 (73.3)	23 (26.7)	86 (44.3)	
Extranodal extension					
 Negative	60 (88.2)	8 (11.8)	68 (35.1)	<0.001	
 Positive	62 (57.9)	45 (42.1)	107 (55.2)	
Lymphatic invasion					
 Negative	65 (82.3)	14 (17.7)	79 (40.7)	0.009	
 Positive	66 (64.7)	36 (35.3)	102 (52.6)	
Vascular invasion					
 Negative	108 (75.0)	36 (25.0)	144 (74.2)	0.119	
 Positive	23 (62.2)	14 (37.8)	37 (19.1)	
Perineural invasion					
 Negative	129 (73.3)	47 (26.7)	176 (90.7)	0.130	
 Positive	2 (40.0)	3 (60.0)	5 (2.6)	
Surgical margin					
 Negative	100 (75.8)	32 (24.2)	132 (68.0)	0.193	
 Positive	31 (66.0)	16 (34.0)	47 (24.2)	
Locoregional recurrence					
 Negative	100 (73.5)	36 (26.5)	136 (70.1)	0.256	
 Positive	40 (69.0)	18 (31.0)	58 (29.9)	
Distant metastasis					
 Negative	114 (78.6)	31 (21.4)	145 (74.7)	<0.001	
 Positive	12 (50.0)	12 (50.0)	24 (12.4)	
Bold values indicate P < 0.05, statistically significant.

Pathological T classifications of the tumors were as follows: T1 for 112 patients (60.5%), T2 for 43 patients (23.3%), T3 for 27 patients (14.6%) and T4 for 3 patients (1.6%). In 9 consultation cases pathological T classification could not be obtained. Patients with TDs had larger tumor size (P = .002), with the mean size of tumor in patients with and without TDs detected as 28.8 ± 19.3 mm and 20.2 ± 14.9 mm, respectively.

Lymph node metastases were present in 174 (89.7%) cases. All TMC cases had locoregional lymph node metastases, whereas 156 of 176 TPC cases (88.6%) had lymph node metastases (P = .225). The mean number of metastatic lymph nodes in TPC and TMC cases were 7.9 ± 6.2 (range, 1–28) and 14.3 ± 12.7 (range, 1–45), respectively (P = .061). Lymph node metastases were more frequent in both multifocal (P = .032), and bilateral tumors (P = .015), in tumors with intrathyroidal extension (P = .009), and lymphatic invasion (P < .001).

Adjuvant radioactive iodine (RAI) therapy was administered in 164 of 171 TPC patients (95.9%). In 5 patients status of RAI application could not be obtained. RAI was not applied to 5 patients with thyroid papillary microcarcinoma (tumor size ≤ 10 mm) and in another 2 patients due to lack of adjuvant therapy necessity according to multidisciplinary tumor board decision. None of these 7 patients who did not receive RAI showed locoregional recurrence. The mean follow-up period of the patients was 120.1 ± 53.9 months (range, 4–341 months), with a median follow-up time of 115.2 months.

Locoregional recurrence was detected in 17 patients (8.8%). Eleven TPC cases (6.3%) and 6 TMC cases (33.3%) had locoregional recurrence (P = .002). In 37 TPC patients (22.6%) ultrasonographic evaluation revealed structural recurrent disease, while 66 TPC patients (40.0%) had biochemical recurrence only with increased serum thyroglobulin levels. Distant metastasis was identified in 27 patients (13.9%). Sites of distant metastases were as follows: lung metastasis in 17 patients, bone metastasis in 3 patients, lung, liver, and bone metastasis in 4 patients, lung and bone metastasis in 3 patients. Distant metastases were more common in tumors with extrathyroidal extension (P = .001). Presence of perineural invasion (P = .032) and positive surgical margins (P = .027) were also associated with distant metastasis.

The 10 and 15-year RFS of the patients were 89.0% and 83.0%, respectively. Mean estimated RFS time for all cases, TD negative and TD positive cases were: 288.2 (±14.5), 297.4 (±15.6) and 252.0 (±25.9) months, respectively (P = .208; Fig. 3). The 10 and 15-year OS of the patients were 92.4% and 84.1%, respectively. Mean estimated OS time for all cases, TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002; Fig. 4). In addition, sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS.

Figure 3. Recurrence-free survival for cases with and without tumor deposits.

Figure 4. Overall survival for cases with and without tumor deposits.

Since TPC and TMC are two distinct neoplasms of the thyroid with different biological behavior, the case series were evaluated individually, as well. In TPC cases, extrathyroidal extension and TDs were significantly correlated with distant metastasis; whereby distant metastasis detected in 15 of 54 TPC cases (27.8%) with extrathyroidal extension (P = .001), and in 12 of 41 cases (29.3%) with TDs (P = .002). In addition, bilaterality (P = .018), presence of tumor capsule (P = .034), intrathyroidal extension (P = .006), and lymphatic invasion (P < .001) were significantly correlated with locoregional lymph node metastases. Age at diagnosis (P < .001) and tumor size (P = .004) were also significantly correlated with OS in TPC cases.

Nevertheless, in TMC case series which consisted of 18 patients, there was no statistically significant correlation between TDs and the prognostic markers. Only male sex (P = .025) and number of metastatic lymph nodes (P = .026) were significantly associated with OS in TMC cases.

In multivariate logistic regression analysis, that was performed based on prognostic factors identified by univariate analysis, both for RFS and OS, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005; OR: 1.053, 95% CI: 1.016–1.091). Cox regression analysis could not be performed, since coefficients did not converge for split files of TPC and TMC cases, and statistical modeling could not be done.

4. Discussion

Thyroid carcinomas, particularly well differentiated TPCs are one of the most common cancers encountered in routine clinical practice. In our thyroid carcinoma case series who had cervical lymph node sampling and/ or dissection, TDs were detected in 27.8%. The incidence of TDs varies between 16.6% and 43.9% in colorectal carcinomas,[10,11] 17.8% and 24.0% in gastric carcinomas,[4,22] 17.1% in head and neck carcinomas,[6] 28.0% in salivary gland tumors,[8] 24.6% in esophageal carcinomas,[23] and 29.0% in breast carcinomas.[9] In our case series, 44 patients with TPC (25.0%) and 10 patients with TMC (55.6%) had TDs. Although TPC and TMC are completely different neoplasms of the thyroid, in terms of both cells of origin, and clinical presentation and biological behavior, presence of TDs are investigated and presented in this study regardless of variances in distinct tumor types of the thyroid.

Evaluation of TDs and distinction between TDs and metastatic lymph nodes may be challenging from time to time, and both intra- and interobserver variability exists. Nevertheless, TDs are different from metastatic lymph nodes, and according to Goldstein and Turner their prognostic significance should not be considered equally.[2,12] The origin and developmental mechanism of TDs is still unclear. Some authors suggest that TDs develop during lymph node metastasis, similar to “in-transit metastases” identified in melanoma cases, and that the lymphatic forming deposits have smooth contours, whereas some others propose perineural or perivascular spread, in which the deposits have irregular contours.[1] In addition, some authors suggest that TDs are generated from the extracapsular extension of lymph node metastasis, and therefore represent lymph nodes with extensive extranodal extension.[11]

There is an ongoing debate in the literature regarding recognition of TDs morphologically. Similar to arguments about mechanisms of TD formation, and questions concerning the routes of dissemination, microscopic evaluation is unsettled as well.[1] In the latest TNM classification of colorectal carcinomas, existence of TDs change the nodal status to pN1c, only if no metastatic regional lymph nodes are detected on pathological examination, and only if they are not associated with residual lymph nodes and vascular or neural structures.[14,24] This definition seems to restrict the evaluation of TDs that is already challenging, however, the prognostic significance of TDs in the literature have been demonstrated in various organ cancers.[4–6,9,10,22,25] This case series of thyroid carcinomas support the aggressive behavior pattern of TDs in these tumors, as well.

Our case series mainly consisted of TPC and TMC, since only patients with cervical lymph node sampling/dissection were selected. Among these patients, TDs were significantly more common in TMCs (P = .006). It is well known that the incidence of locoregional lymph node metastases is higher in TPC and TMC cases among different thyroid malignancies, and TMC cases in particular have nodal metastases as much as 81%, when central and ipsilateral lymph nodes are considered.[26,27] In our case series, all TMCs and 89.0% of TPC cases had locoregional lymph node metastases (P = .368). The mean number of metastatic lymph nodes in TMC cases was more than that of TPCs as well, although not statistically significant (P = .061). However, number of metastatic lymph nodes (P = .026) were significantly associated with OS in TMC cases.

In a meta-analysis which evaluates multifocality in thyroid cancer, high association between multifocality and lymph node metastases, extrathyroidal extension, and tumor size was reported. Multifocality and bilaterality in thyroid carcinomas have been reported between 18% and 87%, and 13% and 71% of the cases, respectively.[28] In our series, the existence of TDs was significantly associated with tumor size (P = .002), multifocality of the tumor (P = .017), lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). A number of studies have shown adverse prognostic feature of multifocality and/or bilaterality in thyroid carcinomas.[29–31] Similarly, TDs were more frequent in multifocal tumors (P = .017) in our study. In addition, lymph node metastases were more frequent in both multifocal (P = .032), and bilateral tumors (P = .015). There are authors in the literature who recommend prophylactic central lymph node dissection in multifocal thyroid carcinomas.[32]

In this case series, TDs were significantly associated with distant metastasis in TPC cases (P = .002), although not demonstrated in multivariate analysis. In our previous study, we had shown that the probability of distant metastasis was 3.3 times higher in breast cancer patients with TDs.[9] Jiang et al[33] has also reported that TDs are significant in predicting distant metastasis after rectal cancer surgery. Yabata et al[34] suggests that the prognostic impact of TDs on OS is between that of lymph node metastasis and distant metastasis. They have shown that the importance of TDs is overlooked, if they are accepted as metastatic lymph nodes. Thus, recognition of TDs and defining their presence individually in pathology reports is significant.

The most important limitation of this study is that it was performed in a single institution with a relatively small sample size. In addition, some clinicopathological information of the patients could not be obtained. Hence, statistical modeling and Cox regression analysis could not be performed thoroughly to give valid statistical results. Studies including more patients are needed to elucidate the prognostic impact of TDs in thyroid carcinoma cases.

5. Conclusion

Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors. Therefore, we suggest that cervical lymph node specimens should be meticulously dissected in pathology laboratories, and the existence of TDs should be defined thoroughly in the pathology reports.

Author contributions

Conceptualization: Merih Guray Durak, Ahmet Omer Ikiz, Sulen Sarioglu.

Data curation: Merih Guray Durak, Deniz Gokcay, Serra Begum Emecen, Ozhan Ozdogan, Ali Ibrahim Sevinc, Ersoy Dogan, Nuri Karabay.

Formal analysis: Hulya Ellidokuz.

Methodology: Hulya Ellidokuz.

Supervision: Ahmet Omer Ikiz, Sulen Sarioglu.

Writing – original draft: Merih Guray Durak.

Writing – review & editing: Merih Guray Durak, Ahmet Omer Ikiz, Sulen Sarioglu.

Abbreviations:

AJCC American Joint Committee on Cancer

OS overall survival

RAI radioactive iodine

RFS recurrence free survival

TD tumor deposit

TMC thyroid medullary carcinoma

TPC thyroid papillary carcinoma.

The authors have no funding and conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Guray Durak M, Gokcay D, Emecen SB, Ozdogan O, Sevinc AI, Ikiz AO, Dogan E, Karabay N, Ellidokuz H, Sarioglu S. Tumor deposits in thyroid carcinomas. Medicine 2024;103:29(e38952).
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References

[1] Sarioglu S . Tumor deposits; mechanisms, morphology, and differential diagnosis. In: Sarioglu S , editor. Tumor deposits. Mechanism, morphology and prognostic implications. Switzerland: Springer; 2018:37–55.
[2] Goldstein NS Turner JR . Pericolonic tumor deposits in patients with T3N+M0 colon adenocarcinomas: markers of reduced disease free survival and intraabdominal metastases and their implications for TNM classification. Cancer. 2000;88 :2228–38.10820343
[3] Sun Z Wang ZN Xu YY . Prognostic significance of tumor deposits in gastric cancer patients who underwent radical surgery. Surgery. 2012;151 :871–81.22386276
[4] Ersen A Unlu MS Akman T . Tumor deposits in gastric carcinomas. Pathol Res Pract. 2014;210 :565–70.24726262
[5] Yildiz B Etiz D Dal P . Tumor deposits: prognostic significance in gastric cancer patients. J BUON. 2016;21 :1476–81.28039711
[6] Sarioglu S Akbulut N Iplikci S . Tumor deposits in head and neck carcinomas. Head Neck. 2016;38 (Suppl 1 ):E256–60.25546631
[7] Shang QX Yang YS Xu LY Li EM Hu WP Chen LQ . Prognostic significance and role in TNM stage of tumor deposits in esophageal cancer. J Thorac Dis. 2017;9 :4461–76.29268516
[8] Sarioglu S Kilicarslan E Aydin B . Tumor deposits in salivary gland tumors. Pathol Int. 2018;68 :183–9.29465761
[9] Durak MG Canda T Yilmaz B . Prognostic importance of tumor deposits in the ipsilateral axillary region of breast cancer patients. Pathol Oncol Res. 2019;25 :577–83.30368727
[10] Ueno H Mochizuki H Hashiguchi Y . Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging. Am J Clin Pathol. 2007;127 :287–94.17210518
[11] Puppa G Maisonneuve P Sonzogni A . Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging. Mod Pathol. 2007;20 :843–55.17491597
[12] Nagtegaal ID Knijn N Hugen N . Tumor deposits in colorectal cancer: improving the value of modern staging - a systematic review and meta-analysis. J Clin Oncol. 2017;35 :1119–27.28029327
[13] Moon JY Lee MR Ha GW . Prognostic value of tumor deposits for long-term oncologic outcomes in patients with stage III colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2022;37 :141–51.34595585
[14] Amin MB Edge SB Greene FL . AJCC Cancer Staging Manual. 8th edn. New York: Springer; 2017.
[15] Cipriani NA . Prognostic parameters in differentiated thyroid carcinomas. Surg Pathol Clin. 2019;12 :883–900.31672296
[16] WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol 10). Available at: https://tumourclassification.iarc.who.int/chapters/53.
[17] Ito Y Miyauchi A Kihara M Kobayashi K Miya A . Prognostic values of clinical lymph node metastasis and macroscopic extrathyroid extension in papillary thyroid carcinoma. Endocr J. 2014;61 :745–50.24739332
[18] Glikson E Alon E Bedrin L Talmi YP . Prognostic factors in differentiated thyroid cancer revisited. Isr Med Assoc J. 2017;19 :114–8.28457063
[19] Kebebew E Ituarte PH Siperstein AE Duh QY Clark OH . Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000;88 :1139–48.10699905
[20] Erovic BM Kim D Cassol C . Prognostic and predictive markers in medullary thyroid carcinoma. Endocr Pathol. 2012;23 :232–42.23150029
[21] Ueno H Mochizuki H Shirouzu K . Study Group for Tumor Deposits without Lymph Node Structure in Colorectal Cancer projected by the Japanese Society for Cancer of the Colon and Rectum. Multicenter study for optimal categorization of extramural tumor deposits for colorectal cancer staging. Ann Surg. 2012;255 :739–46.22395093
[22] Lee HS Lee HE Yang HK Kim WH . Perigastric tumor deposits in primary gastric cancer: implications for patient prognosis and staging. Ann Surg Oncol. 2013;20 :1604–13.23184289
[23] Zhang HD Tang P Duan XF . Extranodal metastasis is a powerful prognostic factor in patients with adenocarcinoma of the esophagogastric junction. J Surg Oncol. 2013;108 :542–9.24018956
[24] Sarioglu S . Tumor deposits in colorectal cancer. In: Sarioglu S , editor. Tumor Deposits. Mechanism, Morphology and Prognostic Implications. Switzerland: Springer; 2018:57–81.
[25] Jin M Roth R Rock JB Washington MK Lehman A Frankel WL . The impact of tumor deposits on colonic adenocarcinoma AJCC TNM staging and outcome. Am J Surg Pathol. 2015;39 :109–15.25229767
[26] Musholt TJ . Classification of locoregional lymph nodes in medullary and papillary thyroid cancer. Langenbecks Arch Surg. 2014;399 :217–23.24306103
[27] Jin LX Moley JF . Surgery for lymph node metastases of medullary thyroid carcinoma: a review. Cancer. 2016;122 :358–66.26539937
[28] Joseph KR Edirimanne S Eslick GD . Multifocality as a prognostic factor in thyroid cancer: a meta-analysis. Int J Surg. 2018;50 :121–5.29337178
[29] Wang W Zhao W Wang H . Poorer prognosis and higher prevalence of BRAF (V600E) mutation in synchronous bilateral papillary thyroid carcinoma. Ann Surg Oncol. 2012;19 :31–6.22033631
[30] Kim HJ Sohn SY Jang HW Kim SW Chung JH . Multifocality, but not bilaterality, is a predictor of disease recurrence/ persistence of papillary thyroid carcinoma. World J Surg. 2013;37 :376–84.23135422
[31] Qu N Zhang L Ji QH . Number of tumor foci predicts prognosis in papillary thyroid cancer. BMC Cancer. 2014;14 :914.25471041
[32] Ozdemir K Harmantepe AT Gonullu E Kocer B Bayhan Z . Should multifocality be an indication for prophylactic central neck dissection in papillary thyroid cancer? Updates Surg. 2023;75 :701–6.36871277
[33] Jiang D Fan X Chen K . Effects of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer: a retrospective study grouped based on the relationship between the bottom of the tumor and peritoneal reflection. J Gastrointest Oncol. 2023;14 :963–79.37201089
[34] Yabata E Udagawa M Okamoto H . Effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases. J Rural Med. 2014;9 :20–6.25648159
