Podejrzenie nowotworu pęcherzykowego czy nowotwór pęcherzykowy? Dylemat patologa i chirurga

  Introduction: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term “Suspicious for Follicular Neoplasm” (SFN) in cytological diagnostics of thyroid carcinoma. Material and methods: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. Results: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] — according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. Conclusions: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis. (Endokrynol Pol 2016; 67 (1): 17–22)    Wstęp: Materiał cytologiczny biopsji aspiracyjnej cienkoigłowej (BAC) tarczycy nie pozwala na zróżnicowanie raków pęcherzykowych, gruczolaków i guzków rozrostowych. Ograniczeniem metody jest brak możliwości określenia obecności torebki guza, jej ewentualnego nacieku oraz angioinwazji. Jednoznaczne rozstrzygnięcie czy mamy do czynienia ze zmianą nowotworową czy łagodną jest możliwe dopiero po badaniu histopatologicznym. Celem pracy było uzasadnienie celowości używania terminu „podejrzenie nowotworu pęcherzykowego” w diagnostyce cytologicznej raka tarczycy. Materiał i metody: Poddano analizie 352 wyniki BAC tarczycy wykonanych w Instytucie Onkologii (IO) w Gliwicach w latach 2010–2015 i ich korelację z rozpoznaniem histopatologicznym. Wyniki: W IO rozpoznanie podejrzenie nowotworu pęcherzykowego (grupa IV wg Systemu Bethesda) postawiono pierwotnie w 352 przypadkach. Leczenie operacyjne podjęto po pierwszej BAC w 6 przypadkach uzyskując potwierdzenie nowotworu w 5 przypadkach w tym jednego raka pęcherzykowego. Powtórna BAC przeprowadzona u 90 pacjentów potwierdziła rozpoznanie grupy IV w 53 przypadkach. Trzecią BAC przeprowadzono u 26 chorych, uzyskując kolejnych 14 rozpoznań grupy IV. Leczeniu operacyjnemu poddano 26 pacjentów na 352 rozpoznania nowotworu pęcherzykowego, uzyskując potwierdzenie nowotworu w 19 przypadkach, co stanowi 73% w tym raka 5 razy. Wnioski: Wysoka dodatnia wartość predykcyjna PPV = 73% rozpoznania „podejrzenie nowotworu pęcherzykowego” uzasadnia podjęcie leczenia operacyjnego w każdym przypadku tego rozpoznania. (Endokrynol Pol 2016; 67 (1): 17–22)

Kliniczne znaczenie rozpoznania zmiany pęcherzykowej bliżej nieokreślonej (grupa III wg Systemu Bethesda) w biopsji aspiracyjnej cienkoigłowej (BAC)

  Introduction: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). Material and methods: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. Results: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of “Papillary Thyroid Carcinoma” and one “Suspicious for Papillary Thyroid Carcinoma”. From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was “Suspicious for Malignancy”. In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. Conclusions: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment. (Endokrynol Pol 2016; 67 (1): 12–16)    Wstęp: Zmiana pęcherzykowa bliżej nieokreślona (grupa III) należy do najbardziej kontrowersyjnej kategorii systemu Bethesda. Brak jest polskich opracowań określających stopień ryzyka wystąpienia nowotworu złośliwego po rozpoznaniu zmiany z grupy III. Celem pracy było określenie ryzyka złośliwości po rozpoznaniu zmiany pęcherzykowej bliżej nieokreślonej w materiale Centrum Onkologii w Gliwicach. Materiał i metody: Analizie poddano 395 rozpoznań z grupy III BAC tarczycy wykonanych w latach 2010–2015. Oceniono zgodność pierwotnego rozpoznania grupy III z rozpoznaniami z kolejnych BAC i wynikami badań histopatologicznych. Wyniki: Na 395 rozpoznań grupy III zoperowano ze wskazań klinicznych 27 pacjentów i rozpoznano 6 raków. Ponowną BAC wykonano w 180 przypadkach i pierwotne rozpoznanie potwierdzono w 41 przypadkach. Po drugiej BAC 2-krotnie rozpoznano raka brodawkowatego lub jego podejrzenie. U 8 operowanych w tej serii potwierdzono wcześniejsze cytologiczne rozpoznanie raka u 2. Trzecią i kolejne BAC wykonano u 46 pacjentów i w jednym przypadku podejrzewano raka. Ryzyko raka w zmianie pęcherzykowej bliżej nieokreślonej w analizowanym materiale wynosi 2,78%. Uwzględniając wszystkie powtórnie wykonane 56 BAC, w których potwierdzono pierwotne rozpoznanie grupy III, ryzyko maleje do 2,43%. Wnioski: Rozpoznanie zmiany pęcherzykowej bliżej nieokreślonej przy braku wskazań klinicznych nie jest podstawą do wszczęcia postępowania chirurgicznego. (Endokrynol Pol 2016; 67 (1): 12–16)

Wytyczne dla laboratoriów genetyki nowotworów litych

Niniejsze wytyczne skierowane są do laboratoriów wykonujących diagnostyczne badania genetyczne technikami biologii molekularnej i cytogenetyki molekularnej (FISH) w zakresie genetyki nowotworów litych zarówno w obszarze zaburzeń genetycznych dziedzicznych, jak i nabytych. Diagnostyczne badanie genetyczne jest wykonywane w celu identyfikacji zaburzeń w DNA komórek człowieka. Przestrzeganie niniejszych zasad ma na celu zapewnienie wysokiego poziomu usług medycznych świadczonych przez laboratoria

Salivary Concentrations of Chemerin, α-Defensin 1, and TNF-α as Potential Biomarkers in the Early Diagnosis of Colorectal Cancer

Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α in colorectal cancer (CRC) patients and in a healthy control group. The concentration of these proteins was simultaneously determined in the serum of subjects. We also aimed to assess the correlation of these results and selected clinicopathological features. This prospective study was comprised of 39 CRC patients and 40 control group patients. Salivary and serum concentrations were determined by enzyme immunoassays. The salivary and serum concentrations of chemerin, α-defensin 1, and TNF-α were significantly higher in cancer patients compared to the control group. No correlation was found between concentrations of the proteins and the clinical stage of cancer and tumor location. The ROC curve analysis showed that although salivary concentrations of all proteins showed 100% sensitivity and 100% specificity, serum concentrations of the analyzed proteins were characterized by 100% sensitivity and over 90% specificity. The assessment of chemerin, α-defensin 1, and TNF-α concentrations in saliva seem to have great potential as quick and useful biomarkers in the early diagnosis of CRC

Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV−) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients

Analysis of Selected Nutritional Parameters in Patients with HPV-Related and Non-HPV-Related Oropharyngeal Cancer before and after Radiotherapy Alone or Combined with Chemotherapy

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: The analysis included 127 patients with OPC who underwent radiotherapy (RT) alone, or in combination with chemotherapy (CRT), in the I Radiation and Clinical Oncology Department of Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (formalin-fixed, paraffin-embedded) tissue material and/or extracellular circulating HPV DNA. Basic anthropometric and biochemical parameters before and after RT/CRT were compared between the HPV- and HPV+ groups. The effect of NS on survival was also analyzed. Results: In both groups, a significant decrease in all analyzed nutritional parameters was noted after RT/CRT (p < 0.01). CRT caused significant weight loss and decreases in BMI, albumin, total lymphocyte count (TLC), and hemoglobin concentration, as well as an increase in the Nutritional Risk Score (NRS) 2002, in HPV- and HPV+ patients. A significant decrease in prealbumin levels after CRT was noted only in HPV+ patients. RT caused a significant decrease in hemoglobin concentration and TLC in HPV- patients. There were no significant differences regarding other nutritional parameters after RT in either group. RT did not have negative impact on body mass index (BMI), weight, NRS, CRP, Alb, Prealb, or PNI. Overall survival (OS) and disease-free survival (DFS) were significantly better in patients with a higher BMI in the HPV- group (OS, p = 0.011; DFS, p = 0.028); DFS was significantly better in patients with C-reactive protein (CRP) < 3.5 g/dL in the HPV- (p = 0.021) and HPV+ (p = 0.018) groups, and with total lymphocyte count (TLC) >1.28/mm3 in the HPV+ group (p = 0.014). Higher NRS 2002 was an independent adverse prognostic factor for OS and DFS in HPV-, but not in the HPV+ group. Kaplan–Meier analysis showed that both OS and DFS were significantly better in HPV- patients with lower NRS 2002 scores. However, this relationship was not observed in the HPV+ group. Conclusions: Regardless of HPV status, patients with OPC can develop malnutrition during RT/CRT. Therefore, nutritional support during RT/CRT is required in patients with HPV- and HPV+ OPC

Determinants of the level of circulating-tumor HPV16 DNA in patients with HPV-associated oropharyngeal cancer at the time of diagnosis

Abstract Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment