10.14639/0392-100X-N1515
Objective. Thyroid nodules with indeterminate cytology represent 20% of all thyroid nodules. Inflammation plays an important role in cancer. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent prognostic scores in numerous cancers, although no study has documented their role in cytology indeterminate nodules. The aim of this study is to evaluate the role of LMR, NLR and PLR values as predictors of malignancy in patients with cytology indeterminate nodules. Methods. This retrospective study analysed data from 298 patients with indeterminate thyroid nodule. Anatomopathological and haematological data were analysed, dividing the population into two groups. LMR, NLR and PLR values were determined using ROC curve and data were analysed using independent samples t-test, test of proportions, Fisher’s exact test and univariate and multivariate logistic regression. Results. We found that a baseline LMR value ≥ 4.09 was indicative of benignity of indeterminate nodule. The probability of malignancy in patients with LMR ˂ 4.09 was 26 times higher than patients with a LMR value ≥ 4.09. Conclusions. This study showed that only LMR has shown a concrete probability to find a thyroid cancer in patients with indeterminate nodules. Further studies are necessary to implement tailored treatment.
text/xml
1827-675X
1515
en
Giovanni Docimo
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
platelet-to-lymphocyte ratio
Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules
Text.Serial.Journal
https://www.actaitalica.it/
41
Thyroid
2021-12-21
2021-02-26
2021-12-22
2021-12-22
530-536
1
Giovanni Docimo
2021/12/21
10.14639/0392-100X-N1515
530
Division of Thyroid Surgery, Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, Naples, Italy
1827-675X
platelet-to-lymphocyte ratio
536
Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules
https://www.actaitalica.it/article/download/1515/715
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:530-536; doi: 10.14639/0392-100X-N1515




Thyroid


Evaluation of LMR, NLR and PLR as predictors
of malignancy in indeterminate thyroid nodules
Valutazione di LMR, NLR e PLR come predittori di malignità in noduli tiroidei
indeterminati
Chiara Offi, Roberto Maria Romano, Angelo Cangiano, Marcello Filograna Pignatelli, Giancarlo Candela,
Giovanni Docimo
Division of Thyroid Surgery, Department of Medical and Advanced Surgical Sciences, University of Campania “Luigi Vanvitelli”,
School of Medicine, Naples, Italy


SUMMARY
Objective. Thyroid nodules with indeterminate cytology represent 20% of all thyroid
nodules. Inflammation plays an important role in cancer. Lymphocyte-to-monocyte ratio
(LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are
independent prognostic scores in numerous cancers, although no study has documented
their role in cytology indeterminate nodules. The aim of this study is to evaluate the role of
LMR, NLR and PLR values as predictors of malignancy in patients with cytology indeter-
minate nodules.
Methods. This retrospective study analysed data from 298 patients with indeterminate
thyroid nodule. Anatomopathological and haematological data were analysed, dividing the          Received: February 26, 2021
population into two groups. LMR, NLR and PLR values were determined using ROC curve              Accepted: September 28, 2021
and data were analysed using independent samples t-test, test of proportions, Fisher’s exact
test and univariate and multivariate logistic regression.                                        Correspondence
Results. We found that a baseline LMR value ≥ 4.09 was indicative of benignity of inde-          Chiara Offi
terminate nodule. The probability of malignancy in patients with LMR ˂ 4.09 was 26 times         Department of Medical and Advanced Surgical
higher than patients with a LMR value ≥ 4.09.                                                    Sciences, University of Campania “Luigi Vanvitel-
                                                                                                 li”, School of Medicine, piazza Miraglia 2, 80138
Conclusions. This study showed that only LMR has shown a concrete probability to find
                                                                                                 Naples, Italy
a thyroid cancer in patients with indeterminate nodules. Further studies are necessary to        Tel. +39 081 5665275. Fax +39 081 5665257
implement tailored treatment.                                                                    E-mail: chiara.o@live.com
KEY WORDS: indeterminate thyroid nodule, thyroid cancer, neutrophil-to-lymphocyte
ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio                                Funding
                                                                                                 None.

RIASSUNTO                                                                                        Conflict of interest
Obiettivo. I noduli tiroidei a citologia indeterminata rappresentano il 20% di tutti i noduli    The Authors declare no conflict of interest.
tiroidei. L’infiammazione gioca un ruolo importante nel cancro. LMR, NLR e PLR sono
fattori prognostici indipendenti in numerosi tumori; tuttavia, nessuno studio ha mostrato          How to cite this article: Offi C, Romano RM,
il loro ruolo nei noduli a citologia indeterminata. Questo studio si propone di valutare il        Cangiano A, et al. Evaluation of LMR, NLR
ruolo di LMR, NLR e PLR come predittori di malignità in pazienti con noduli a citologia            and PLR as predictors of malignancy in in-
indeterminata.                                                                                     determinate thyroid nodules. Acta Otorhi-
Metodi. Abbiamo analizzato retrospettivamente i dati di 298 pazienti con nodulo tiroideo           nolaryngol Ital 2021;41:530-536. https://doi.
indeterminato. Abbiamo analizzato i dati anatomopatologici ed ematologici, dividendo la            org/10.14639/0392-100X-N1515
popolazione in due gruppi. I valori cut-off di LMR, NLR e PLR sono stati determinati con
la curva ROC e i dati sono stati esaminati utilizzando il t-test per campioni indipendenti, il   © Società Italiana di Otorinolaringoiatria
                                                                                                 e Chirurgia Cervico-Facciale
test delle proporzioni, il Fisher exact test e la regressione univariata e multivariata.
Risultati. Un valore LMR basale ≥ 4,09 è indicativo di benignità. La probabilità di ne-
                                                                                                                OPEN ACCESS
oplasia nei pazienti con LMR ˂ 4,09 è 26 volte superiore rispetto ai pazienti con valore
LMR ≥ 4,09.                                                                                      This is an open access article distributed in accordance with
                                                                                                 the CC-BY-NC-ND (Creative Commons Attribution-Non-
Conclusioni. Questo studio ha dimostrato che solo un valore di LMR ˂ 4,09 ha una proba-          Commercial-NoDerivatives 4.0 International) license. The
bilità concreta che un nodulo a citologia indeterminata possa essere un cancro.                  article can be used by giving appropriate credit and mentio-
                                                                                                 ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: nodulo tiroideo indeterminato, cancro della tiroide, rapporto neutrofili-         only in the original version. For further information: https://
linfociti; rapporto linfociti-monociti, rapporto piastrine-linfociti                             creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                 Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules




Introduction                                                       (TT) and compare these indices with anatomopathological
                                                                   findings. The routine use of these inflammatory indices can
Papillary thyroid cancer (PTC) represents 90% of all ma-           add information in cytology indeterminate nodules.
lignant thyroid neoplasms 1. Thyroid cancer accounts 3-4%
of new cancer diagnoses annually, representing the most
common endocrine neoplasm 2. The incidence of thyroid              Materials and methods
cancer has increased in past decades due to the increased          We retrospectively collected data on 298 adult patients
incidence of PTC 1. PTC is more frequent in women and              undergoing TT at the Department of Thyroid Surgery of
has a mortality of 1/100,000 deaths per year 3. PTCs are           the University of Campania “Luigi Vanvitelli” from March
indolent tumours, with an incidence of lymph node metas-           2012 until December 2019. All patients had a multinodu-
tases of 30-90% 4. Diagnosis is performed with neck ul-            lar goiter with a cytological diagnosis of indeterminate
trasound associated with fine needle cytology (FNC), al-           thyroid nodule (Tir3a or Tir3b) to FNC, according to the
though non-diagnostic or indeterminate cytology rates are          SIAPEC-IAP classification 5. Clinical and demographics
up to 20% 1,3. Early and accurate diagnosis allow to plan          records were reordered in an electronic database. Anato-
surgery and radiometabolic therapy, considering the high           mopathological findings were evaluated and classified with
percentage of cytology indeterminate neoformations (Tir3a          tumour-node-metastases (TNM) staging, according to the
and Tir3b), it is desirable to identify haematological mark-       American Joint Committee on Cancer (AJCC) staging sys-
ers that can identify PTC at an early stage 5.                     tem (8th edition) 10.
Genetic mutations play a role in risk assessment in inde-          Table I shows the patients enrolled according to the inclu-
terminate cytology. The risk of recurrence in tumours with         sion and exclusion criteria. We included adult patients with:
BRAFV600E mutations versus wild-type BRAFV600E tu-                 multinodular goiter with cytological diagnosis of Tir3a
mours has already been widely evaluated in the literature 1.       and Tir3b to FNC, complete medical history and complete
The genetic mutation profile in indeterminate nodules is           preoperative blood tests. We excluded patients with: preg-
not always valuable in common practice, as this involves           nancy; other histopathological thyroid cancer as medullary
the execution of a second FNC, which is not well accepted          thyroid cancer (MTC) or ATC; previous thyroid tumours;
by the patient. However, a blood sample is a noninvasive,          distant metastases; autoimmune thyroid disease; previous
well-tolerated, safe and inexpensive method and can be             tumours of the head-neck district; neck surgery within
used in screening, diagnosis and follow-up. The immune             5 years; neck radiation therapy; chronic inflammation due
system and inflammatory response are associated with ini-          to HBV, HCV, chronic gastritis, nephritis or gout; immune
tiation, progression, metastasis and prognosis of the can-         or haematological disease; proliferative haemopoietic dis-
cer 6. The inflammatory mediators are neutrophils, lympho-         orders. Moreover, we excluded patients with heart failure,
cytes, monocytes and platelets. Neutrophils and platelets          use of anticoagulant drug, hypertension and diabetes mel-
contribute to tumourogenesis, producing pro-inflammatory           litus. All excluded patients are shown in Figure 1. These
cytokines such as endothelial growth factor (VEGF), tu-            conditions could represent a bias in white blood cell and
mour necrosis factor-α (TNF-α), interleukin-2 (IL-2),              platelet counts.
interleukin-6 (IL-6) and interleukin-10 (IL-10). On the            We divided the population into two groups based on anato-
other hand, monocytes and lymphocytes contribute with              mopathological results: PTC (Group A) and multinodular
anti-tumoural effects 6. The lymphocyte-to-monocyte ratio          goiter (Group B). All patients underwent preoperative blood
(LMR), neutrophil-to-lymphocyte ratio (NLR) and plate-             sample, FNC, neck ultrasound and fiberoptic-laryngoscopy
let-to-lymphocyte ratio (PLR) are independent prognostic           tests in the 30 days prior to surgery. Clinical, demographic
factors in many solid cancers 7. All these ratios can be cal-      data and anatomopathological findings such as histopatho-
culated on routine preoperative blood samples with no ad-          logical type, dimension, capsular invasion, vascular inva-
ditional costs and no discomfort to the patient.                   sion, laterality, unifocality, multifocality and stage were
In the literature it is established that the various ratios        obtained from archive files. Laboratory data, such as white
play an important role in prognosis of high-risk differenti-       blood cells, neutrophils, lymphocytes, monocytes, eosino-
ated thyroid cancer (DTC) and in anaplastic thyroid cancer         phils, basophils and platelets were obtained from archive
(ATC), but there are no studies on the role played in cytol-       data. NLR, LMR and PLR were obtained from the simple
ogy indeterminate nodules 8,9.                                     relationship between the respectively values. All surgical
The aim of this study is to evaluate the LMR, NLR and              procedures were performed by two surgeons (GD and GC).
PLR values in patients with cytology indeterminate nodules         The surgical treatments performed were TT/near total thy-
without mutation analysis undergoing total thyroidectomy           roidectomy (NTT).



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C. Offi et al.




Table I. Patient demographic and clinicopathological data.
 Characteristics                                   Population       Group A           Group B        p-value
 Cases (%)                                           298           59 (19.79)        239 (80.21)     < 0.001
 Sex (%)
   Male                                           63 (21.14)       12 (20.33)         51 (21.33)     0.866
   Female                                        235 (78.46)       47 (79.66)        188 (78.66)
 Age (mean, ± SD)                              50.69 (± 14.73)   49.08 (± 12.88)   51.09 (± 15.15)   0.370
 TNM stage (8th ed.)
   I (%)                                           56 (18.8)       56 (94.91)            NA            NA
   II (%)                                            3 (1)          3 (5.09)
 Mean tumour size in cm (mean, ± SD)                               1.54 (±0.9)           NA            NA
 Laterality of tumour (%)
   Right                                           24 (8.05)       24 (40.7)             NA            NA
   Left                                           35 (11.75)       35 (59.3)
 Cases (%)                                           298           59 (19.79)        239 (80.21)     < 0.001
SD: standard deviation; NA: not applicable.




Figure 1. Flow-chart of eligible patients.



532
                                                                      Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules




Table II. Baseline haematological values.
 Blood values                                          Population                          Group A                            Group B           p-value
 Mean white blood cell (± SD)                         7.30 (± 1.87)                    6.81 (± 1.66)                       7.41 (± 1.9)           0.02
 Mean neutrophils (± SD)                              4.61 (± 1.54)                     4.32 (± 1.5)                      4.68 (± 1.54)           0.62
 Mean lymphocytes (± SD)                              2.07 (± 0.55)                    1.78 (± 0.36)                      2.14 (± 0.57)         < 0.001
 Mean monocytes (± SD)                                0.41 (± 0.13)                    0.50 (± 0.12)                      0.39 (± 0.12)         < 0.001
 Mean eosinophils (± SD)                               0.15 (± 0.1)                    0.14 (± 0.10)                      0.15 (± 0.11)          0.289
 Mean basophils (± SD)                                0.04 (± 0.02)                    0.04 (± 0.03)                      0.38 (± 0.02)          0.784
 Mean platelets (± SD)                              260.370 (± 63.2)                 254.800 (± 53.49)                  262.426 (± 65.15)        0.439
 Mean LMR (± SD)                                      5.61 (± 2.82)                    3.46 (± 0.64)                      6.10 (± 2.94)         < 0.001
 Mean NLR (± SD)                                     2.31 (± 0.82)                     2.26 (± 0.80)                      2.49 (± 0.87)          0.58
 Mean PLR* (± SD)                                  132.878 (± 43.02)                 129.674 (± 43.42)                  145.857 (± 39.13)        0.003
SD: standard deviation; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; *x1000.



Blood samples were taken preoperatively as part of the rou-                                 (80.21% with a mean age of 51.09 ± 15.15), without no sig-
tine preoperative tests and were collected in tubes contain-                                nificant difference between groups. Female patients were
ing ethylenediaminetetraacetic acid (EDTA) to allow study                                   78.46% of the studied population, with a similar percentage
of white blood cell and platelet counts.                                                    in the two groups.
The study protocol was approved by the Ethics Committee                                     The mean blood count values, LMR, NLR and PLR values
of the University of Campania “Luigi Vanvitelli” with pro-                                  are shown in Table II. Mean white blood cells, lymphocytes
tocol AOU4588/2020. Written informed consent was ob-                                        and monocytes were significantly different between groups
tained from all participants. All procedures performed were                                 with a p-values of < 0.001 for lymphocytes and monocytes
in accordance with the Helsinki Declaration.                                                and p-value of 0.018 for white blood cells. Mean LMR and
                                                                                            mean PLR were significantly different between groups, with
Statistical analysis                                                                        a p-value of < 0.001 and 0.009, respectively. NLR showed no
Variables were continuous, described as mean and standard                                   significant difference between groups (p-value 0.057).
deviation, and categorical, described as number of cases                                    In Table III, prognostic scores were evaluated as odds fac-
and percentage. The population was divided in those with                                    tors for presence of the disease; in particular, we noticed
PTC (Group A) and those with benign goiter (Group B),                                       that univariate LMR factor showed an OR of 0.13 (p-value
according to anatomopathological reports. A nonparamet-                                     < 0.001). Moreover, we calculated the univariate OR cancer
ric Wilcoxon-Mann-Whitney independent samples test was                                      when LMR was less than 4.09, which was 26.058 (p-value
performed to compare continuous variables (age, blood                                       < 0.001). Other haematological prognostic factors showed
sample values and LMR, NLR and PLR). Test of Propor-                                        no significant difference in OR.
tions was conducted on categorical variables (number of                                     We calculated the receiver operating characteristic (ROC)
cases based on anatomopathological reports of PTC or                                        curves for LMR, PLR and NLR (Figs. 2-4). The ROC curve
multinodular goiter). Moreover, the chi square test has been                                for LMR had an area under the curve (AUC) of 0.886 ± 0.19
used in order to analyse gender. Odds ratio (OR) was cal-                                   with a cut-off value of 4.09, sensitivity of 84.7% and speci-
culated using univariate and multivariate Logistic Regres-                                  ficity of 82.4%. The ROC curve for PLR had an AUC of
sion. Statistical significance was considered in case of p-                                 0.623 ± 0.39 with a cut-off value of 121.665, sensitivity of
value<0.05. Statistical analysis was performed with SPSS                                    69.5% and specificity of 48.1% (Fig. 3). The ROC curve for
version 23 (SPSS©, Chicago, IL, USA).                                                       NLR has an AUC of 0.58 ± 0.4, with no valid cut-off value
                                                                                            or significant difference between groups (Fig. 4).
Results
Blood samples, clinical and anatomopathological data of
                                                                                            Discussion
298 patients with multinodular thyroid goiter with a cytol-                                 Our study attempted to find a correlation between LMR,
ogy indeterminate nodule, were analysed retrospectively.                                    PLR and NLR and prediction of malignancy or benignity
Baseline demographic and disease characteristics are re-                                    in thyroid nodules with indeterminate cytology (Tir3a and
ported in Table I. Group A had 57 patients (19.79% with a                                   Tir3b). In the literature, various studies have evaluated the
mean age of 49.08 ± 12.88) and Group B had 239 patients                                     values of LMR, PLR and NLR in patients with thyroiditis



                                                                                                                                                            533
C. Offi et al.




Table III. Univariate and multivariate analysis evaluating the odds of PTC.
                                           Univariate OR (95% CI)                               p-value                    Adjusted ORa (95% CI)                        p-value
 NLR                                               0.712 (0.440-1.152)                          0.166                        0.513 (0.61-4.326)                          0.539
 LMR                                               0.130 (0.071-0.238)                         < 0.001                      0.216 (0.028-1.671)                          0.142
 PLR                                               1.001 (0.991-1.012)                          0.825                       1.012 (0.969-1.057)                          0.590
 Cancer when LMR < 4.09                          26.058 (11.898-57.072)                        < 0.001                     2.960 (0.787-11.136)                          0.109
a
  Adjusted for full blood count values (OR: odds ratio; CI: confidential interval; LMR: lymphocytes-to-monocytes ratio; NLR: neutrophil-to-lymphocytes ratio; PLR: platelet-to-lymphocytes
ratio.




Figure 2. ROC curves of LMR (cut-off value 4.09, AUC 0.886 ± 0.1, sensi-                        Figure 3. ROC curves of PLR (cut-off value 121.665, AUC 0.623 ± 0.39,
tivity of 84.7% and a specificity of 82.4%. For LMR < 4.09, univariate OR is                    sensitivity 69.5% and specificity of 48.1%).
26.058 with a p-value < 0.001).


and in patients with differentiated carcinoma on thyroidi-
tis, without finding statistically significant differences 11,12,
but there are no examples of how these values can predict
a greater risk of malignancy in Tir3a and Tir3b nodules.
The aim of our study was to find an instrument that can
identify, at the time of cytology diagnosis, patients with in-
determinate cytology thyroid nodules with a greater risk of
malignancy.
Accurate preoperative diagnosis of thyroid nodules repre-
sents a clinical problem for endocrinologists and endocrine
surgeons. The key role is played by the pathologist who
must cytologically characterise thyroid nodules undergo-
ing FNC to allow the patient to receive tailored treatment.
FNAC is the only exam that can provide a definitive pre-
operative diagnosis with a sensitivity and specificity of 68-
98% and 56-100%, respectively 13,14. The Italian cytological
classification includes the following diagnostic categories:
Tir1, nondiagnostic; Tir1c, cystic; Tir2, negative for neo-                                     Figure 4. ROC curves of NLR (AUC 0.58 ± 0.4, no valid cut-off value found).



534
                                                  Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules




plasia; Tir3a, indeterminate low risk lesion; Tir3b, inde-          The role of low NLR values as an independent prognos-
terminate high risk lesion; Tir4, suspicious for malignant          tic factor in the prognosis of numerous solid neoplasm and
neoplasm; and Tir5, positive for malignancy 5. The inde-            thyroid cancer has been widely ascertained in the litera-
terminate lesions remain a large and controversial field re-        ture 7,21,22. Neutrophils produce VEGF, inhibit TNF-α and
garding clinical and surgical treatment of thyroid nodules.         promote secretion of IL-2, IL-6 and IL-8; a high neutrophils
The literature suggests that these lesions represent up to          count facilitates tumour progression and invasion, while a
20% of cytological diagnoses and represent a grey area in           low lymphocyte count reduces antineoplastic activity 6. In
which both benign and malignant nodules are included 15,16.         our study, found no significant difference in NLR or a valid
These data suggest that the high percentage of thyroid nod-         cut-off value, due to the low AUC found (AUC 0.58 ± 0.4).
ules with indeterminate cytology is associated with many
thyroid surgeries, a cause of further morbidity and higher
costs for increase in costs. Literature data suggests that ap-
                                                                    Conclusions
proximately 70% of thyroid surgeries are unnecessary. Ti-           This study showed that only LMR has a concrete prob-
r3a nodules, indeed, have a risk of malignancy of less than         ability to identify a thyroid cancer in indeterminate nodule
10%, while Tir3b nodules have a risk of malignancy of 15-           patients. Even if mean PLR had a significant difference be-
30%. Identification of haematological indices that can pre-         tween the two groups, univariate analysis with PLR showed
dict the benignity or malignancy of indeterminate nodules           no significant results. Further studies are necessary to clar-
could significantly reduce the percentage of overtreatment.         ify and validate the specific role of LMR and PLR. Our
Inflammatory cells in blood can promote cancer initiation,          hope is that these scores can be used to predict malignity of
progression and worsen prognosis. The mediators of inflam-          the indeterminate thyroid nodule to be submitted to surgery
matory response are neutrophils, lymphocytes, monocytes             to avoid delays in treatment and/or avoid overtreatment by
and platelets. Monocytes and lymphocytes are anti-tumour-           implementing tailored therapy.
al mediators. Low levels of lymphocytes and monocytes
are associated with poor prognosis and have been observed
in advanced cancer stages 7. Monocytes induce apoptosis
                                                                    References
of cancerous cells to reduce angiogenesis, thus decreasing
                                                                    1
                                                                        Haugen BR, Alexander EK, Bible KC, et al. American Thyroid As-
                                                                        sociation management guidelines for adult patients with thyroid
invasion and progression of cancer 17,18. In the literature,            nodules and differentiated thyroid cancer: the American Thyroid
low LMR values are associated with poor prognosis and a                 Association guidelines task force on thyroid nodules and differenti-
high risk of recurrence of ATC and DTC 19,20. In our study,             ated thyroid cancer. Thyroid 2015;26:1-133. https://doi.org/10.1089/
                                                                        thy.2015.0020
mean LMR value showed a significant difference between
                                                                    2
                                                                        Kitahara CM, Sosa JA. The changing incidence of thyroid can-
the two groups (p-value < 0.001) and univariate analysis
                                                                        cer. Nat Rev Endocrinol 2016;12:646-653. https://doi.org/10.1038/
had a p-value of < 0.001. We calculated a cut-off value of              nrendo.2016.110
4.09 (AUC 0.886 ± 0.1) with a sensitivity of 84.7% and a            3
                                                                        Cabanillas ME, McFadden DG, Durante C. Thyroid can-
specificity of 82.4%. An LMR value ˃ 4.09 is indicative of              cer.     Lancet     2016;388:2783-2795.        https://doi.org/10.1016/
benignity of the indeterminate nodule. Moreover, the uni-               S0140-6736(16)30172-6
variate OR when LMR value is lower than 4.09 was ˃ 26               4
                                                                        Gambardella C, Patrone R, Di Capua F, et al. The role of prophy-
                                                                        lactic central compartment lymph node dissection in elderly patients
with a p-value of < 0.001. This means that the probability              with differentiated thyroid cancer: a multicentric study. BMC Surg
of disease in patients with LMR lower than 4.09 is 26 times             2019;18(Suppl 1):110. https://doi.org/10.1186/s12893-018-0433-0
higher than a patient with LMR value greater than 4.09.             5
                                                                        Nardi F, Basolo F, Crescenzi A, et al. Italian Consensus for the clas-
Moreover, univariate OR LMR was 0.130 with a p-value                    sification and reporting of thyroid cytology. J Endocrinol Invest
of < 0.001. We can interpret this outcome that the higher               2014;37:593-599. https://doi.org/10.1007/s40618-014-0062-0
the LMR, the higher the probability that there is no cancer.
                                                                    6
                                                                        Dupré A, Malik HZ. Inflammation and cancer: what a surgical on-
                                                                        cologist should know. Eur J Surg Oncol 2018;44:566-570. https://doi.
According to the recent literature, there are few correla-              org/10.1016/j.ejso.2018.02.209
tions between PLR and risk of recurrence and prognosis of           7
                                                                        Mercier J, Voutsadakis IA. Comparison of hematologic and other
patients with thyroid cancer 21-23. In our population study,            prognostic markers in metastatic colorectal cancer. J Gastrointest
we observed a significant differences in mean PLR value                 Cancer 2019;50:493-506. https://doi.org/10.1007/s12029-018-0108-1
between the two groups (p-value 0.009), but OR showed no            8
                                                                        Song L, Zhu J, Li Z, et al. The prognostic value of the lymphocyte-
                                                                        to-monocyte ratio for high-risk papillary thyroid carcinoma. Cancer
significant significance. We calculated a PLR cut-off value
                                                                        Manag Res 2019;11:8451-8462. https://doi.org/10.2147/CMAR.
of 121.665 (AUC 0.623 ± 0.39) with a sensitivity of 69.5%               S219163
and a specificity of 48.1%, but it cannot be considered as a        9
                                                                        Yamazaki H, Sugino K, Matsuzu K, et al. Inflammatory biomarkers
valid cut-off value.                                                    and dynamics of neutrophil-to-lymphocyte ratio in anaplastic thyroid




                                                                                                                                         535
C. Offi et al.




     carcinoma. Endocrine 2020;70:115-122. https://doi.org/10.1007/             17
                                                                                     Chanmee T, Ontong P, Konno K, et al. Tumor-associated macrophag-
     s12020-020-02313-5                                                              es as major players in the tumor microenvironment; Cancers (Basel)
10
     Zanoni DK, Patel SG, Shah JP. Changes in the 8th Edition of the                 2014;6:1670-1690. https://doi.org/10.3390/cancers6031670
     American Joint Committee on Cancer (AJCC) staging of head and              18
                                                                                     Goswami KK, Ghosh T, Ghosh S, et al. Tumor promoting role of
     neck cancer: rationale and implications. Curr Oncol Rep 2019;21:52.             anti-tumor macrophages in tumor microenvironment. Cell Immunol
     https://doi.org/10.1007/s11912-019-0799-x                                       2017;316:1-10. https://doi.org/10.1016/j.cellimm.2017.04.005
11
     Ari A, Gunver F. Comparison of neutrophil-lymphocyte ratio and             19
                                                                                     Yokota M, Katoh H, Nishimiya H, et al. Lymphocyte-monocyte ratio
     platelet-lymphocyte ratio in patients with thyroiditis and papillary tu-
     mors comparative study. J Int Med Res 2019;47:2077-2083. https://               significantly predicts recurrence in papillary thyroid cancer. J Surg
     doi.org/10.1177/0300060519838392                                                Res 2020;246:535-543. https://doi.org/10.1016/j.jss.2019.09.034
12
     Kutluturk F, Gul SS, Sahin S, et al. Comparison of mean platelet
                                                                                20
                                                                                     Ahn J, Song E, Oh HS, et al. Low lymphocyte-to-monocyte ratios
     volume, platelet count, neutrophil/ lymphocyte ratio and platelet/              are associated with poor overall survival in anaplastic thyroid car-
     lymphocyte ratio in the euthyroid, overt hypothyroid and subclinical            cinoma patients. Thyroid 2019;29:824-829. https://doi.org/10.1089/
     hyperthyroid phases of papillary thyroid carcinoma. Endocr Metab                thy.2018.0684
     Immune Disord 2019;19:859-865. https://doi.org/10.2174/18715303            21
                                                                                     Ceylan Y, Kumanlıoğlu K, Oral A, et al. The correlation of clinico-
     19666190206125545
                                                                                     pathological findings and neutrophil-to-lymphocyte and platelet-
13
     Gharib H. Changing trends in thyroid practice: understanding nodular            to-lymphocyte ratios in papillary thyroid carcinoma. Mol Imag-
     thyroid disease. Endocr Pract 2004;10:31-39. https://doi.org/10.4158/           ing Radionucl Ther 2019;28:15-20. https://doi.org/10.4274/mirt.
     EP.10.1.31
                                                                                     galenos.2018.60490
14
     Yassa L, Cibas ES, Benson CB, et al. Long-term assessment of a mul-
     tidisciplinary approach to thyroid nodule diagnostic evaluation. Can-
                                                                                22
                                                                                     Seretis C, Gourgiotis S, Gemenetzis G, et al. The significance of
     cer 2007;111:508-516. https://doi.org/10.1002/cncr.23116                        neutrophil/lymphocyte ratio as a possible marker of underlying papil-
                                                                                     lary microcarcinomas in thyroidal goiters: a pilot study. Am J Surg
15
     Renshaw AA. Should “Atypical follicular cells” in thyroid fine-nee-
     dle aspirates be subclassified? Cancer Cytopathol 2010;118:186-189.             2013;205:691-696. https://doi.org/10.1016/j.amjsurg.2012.08.006
     https://doi.org/10.1002/cncy.20091                                         23
                                                                                     Ozmen S, Timur O, Calik I, et al. Neutrophil-lymphocyte ratio (NLR)
16
     Faquin WC, Baloch ZW. Fine-needle aspiration of follicular patterned            and platelet-lymphocyte ratio (PLR) may be superior to C-reactive
     lesions of the thyroid: diagnosis, management, and follow-up accord-            protein (CRP) for predicting the occurrence of differentiated thy-
     ing to National Cancer Institute (NCI) recommendations. Diagn Cy-               roid cancer. Endocr Regul 2017;51:131-136. https://doi.org/10.1515/
     topathol 2010;38:731-739. https://doi.org/10.1002/dc.21292                      enr-2017-0013




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