Unknown Primary Location Research Articles

Serum and urinary 5-hydroxyindolacetic acid, serotonin, chromogranin A, and NT-proBNP for the detection of carcinoid heart disease.

The aim of this study was to evaluate the performance of different biomarkers for the detection of carcinoid heart disease (CHD) in neuroendocrine tumours (NETs), in particular serum 5-HIAA (s5HIAA). An explorative ancillary study of the French CrusoeNET cohort. Patients managed in the Lyon-EURACAN Center of Excellence (CoE) were included when they were aged of at least 18 years, treated and followed for an advanced/metastatic ileum or lung NET, a NET irrespective of the primary location or from unknown primary location but with clinical CS, and/or elevation of urinary 5-HIAA (u5HIAA) twice greater than the upper limit of normal. All patients included had 1 available serum stored within the local biobank between January 2021 and April 2022. Echocardiography was performed by 1 of the 3 expert cardiologists of the Lyon-EURACAN-CoE. We included 138 patients with NETs, mainly of the small intestine and lung, and 19 of them had a CHD. Analysis showed that s5HIAA was well correlated with u5HIAA (ρ = 0.824 [0.76-0.88], P < .0001) and was a good biomarker for CHD detection (receiver operating characteristic curve = 0.85 [0.75-0.94], P < .0001). Using a threshold value of 757 nmol/L, the sensitivity and specificity for the detection of CHD were 84% and 80%, respectively. s5HIAA is highly sensitive and specific for CHD detection. It could be used as a pre-screening tool in centres where systematic and regular echocardiography by an expert cardiologist is not performed in this population.

Interest of Integrated Whole-Body PET/MR Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms: A Retro-Prospective Study.

Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with 18F-6-fluoro-L-dihydroxyphenylalanine (18FDOPA, n = 30), 18F-fluoro-2-deoxy-D-glucose (18FDG, n = 21), or 68Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (68Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6-12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. The mean age was 61 [extremes, 31-92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7-381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure.

Tumor behaviour in neuroendocrine tumors (NETs) of unknown primary versus known primary site location

Tumor behaviour in neuroendocrine tumors (NETs) of unknown primary versus known primary site location

Patient-reported outcomes: The unmet needs of the gastrointestinal cancer community.

731 Background: According to the World Health Organization International Agency for Research on Cancer, gastrointestinal (GI) cancers account for 1 in 4 cancer cases and 1 in 3 cancer-related deaths worldwide. An estimated 4.8 million new cases of GI cancers and 3.4 million related deaths occur annually. Understanding the need for increased GI cancer awareness, patient education and support, the GI Cancers Alliance developed a series of engagement activities for the GI cancer community as a needs assessment to identify critical gaps in support services, fragmented education, and disease awareness. Methods: Our 12-month patient-reported outcomes (PRO) research included an online anonymous survey, individual and small group interviews, focus groups, advisory boards, and an interactive workshop at the 2023 American Society of Clinical Oncology annual meeting. 1,122 patients participated during this 12-month PRO research period. Participants reported being diagnosed with one of the following GI cancer primary tumor types: Anus (3%), Appendix (2%), Bile Duct (6%), Colon (19%), Esophagus (7%), Gallbladder (5%), Gastric (14%), GI NET / GI Carcinoid Tumor (3%), Liver (7%), Pancreas (6%), Small Intestine (4%), Rectum (23%), Unknown primary location (1%). Results: Overarching areas of unmet need include: health disparities throughout the care continuum for underserved populations (21%); lack of adequate precision oncology patient education, including biomarker education and testing (19%); the rise of early-age onset (EAO) in GI cancers and the unique needs of the young adult (YA) population (18%); nutritional wellness education (17%); insufficient support for family caregivers and caregiver respite services (16%) scarcity of patient-centered care and adequate patient-clinician communication (11%). Conclusions: Our PRO research underscores the unmet needs and gaps in support services of the GI cancer community. Our global call to action includes partnering with our 100+ member organizations to amplify the patient voice and patient-lived experience, and cross-collaboration with our community of advocates, patients, caregivers, and clinicians. Our shared call to action and continued collaboration provides a greater impact for our GI cancer community to help meet patient needs and eliminate critical gaps in services.

Transcriptomic profiling of a tissue sample of neuroendocrine cancer with unknown primary localization in order to clarify the diagnosis and select options for antitumor therapy

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PET/CT with &lt;sup&gt;68&lt;/sup&gt;Ga-FAPI in the Diagnosis of Cancer of Unknown Primary Localization. Clinical Case

Purpose: Analysis of a clinical case of detection the primary focus in a patient with metastatic liver damage from cancer of unknown primary localization using PET/CT with 68Ga-FAPI. Material and methods: A patient with metastatic liver damage from CUP underwent a set of diagnostic methods, according to the results of which the primary focus was not detected. PET/CT with 68Ga-FAPI revealed the primary focus, which was localize in the left breast and did not accumulate 18F-FDG. According to mammography, the formation in the left breast was regard as benign changes (BI-RADS-2). According to the results of histological examination, the node in the left breast is invasive ductal cancer. Conclusion: PET/CT with 68Ga-FAPI can potentially surpass PET/CT with 18F-FDG in the detection of primary tumors in metastases from cancer of unknown primary localization.

THROMBOTIC MICROANGIOPATHY: DIAGNOSTIC CHALLENGES IN THE PRIMARY MULTIPLE NEOPLASM INVOLVEMENT WITH PREVALENT METASTASIS WITH GRANULOMATOSIS INFLAMMATORY FOCUSES.

Patient, who died during the hospital stay, had hemoblastosis and syphilis in the reported medical history. While the patient was examined doctors suspected the presence of malignancy with unknown primary localization with multiple metastatic injuries with clinical and laboratory TTP signs (hemorrhagic syndrome, thrombocytopenia, shystocytosis, and non-immune hemolytic anemia). Despite treatment, the general patient's condition progressively worsens with increasing multiple organ decompensation signs. In the final stage of the disease course, after heart arrest and the appearance of clinical death signs CPR measures were performed according to complete guidance, but CRP had no positive effect. Biological death was constated. Considering the criteria of the diagnostic clinical and laboratory dyad (thrombocytopenia and microangiopathic hemolytic anemia), the data of the patholog¬ical examination (multiple metastatic lesions, inflammatory process, tumor intoxication, thrombosis), the combination of manifestations of chronic myeloid leukemia, prostate cancer with multiple metastases, tertiary syphilis served as a condition for the initiation of TTP, which was of decisive importance in the development of the patient's death.

Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features

Cancers of unknown primary (CUP) origin account for ∼3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. CUPLR distinguishes 35 cancer (sub)types with ∼90% recall and ∼90% precision based on cross-validation and test set predictions. We find that structural variant derived features increase the performance and utility for classifying specific cancer types. With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

Abstract 2167: Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features

Abstract Tumor tissue of origin (TOO) is an important factor for guiding treatment decisions. However, TOO cannot be determined for ~3% of metastatic cancer patients that present in the clinic and are categorized as cancers of unknown primary (CUP). As whole genome sequencing (WGS) of tumors is now transitioning from the research domain to diagnostic practice in order to address the increasing demand for biomarker detection, its use for detection of TOO in routine diagnostics also starts becoming within reach. While proof of concept for the use of genome-wide features has been demonstrated before, more complex WGS mutation features, including structural variant (SV) driver and passenger events, have never been integrated into TOO-classifiers even though they bear highly characteristic links with tumor TOO. Using a uniformly processed dataset containing 6820 whole-genome sequenced primary and metastatic tumors (ICGC/PCAWG and Hartwig cohors), we have developed Cancer of Unknown Primary Location Resolver (CUPLR), a random forest based TOO classifier that employs 502 genome-wide features based on simple and complex somatic driver and passenger mutations. Our model is able to distinguish 33 cancer (sub)types with an overall accuracy of 91% and 89% based on cross-validation (n=6139) and hold out set (n=681) predictions, respectively. We found that SV derived features increase the accuracy and utility of TOO classification for specific cancer types. To ensure that predictions are human-interpretable and suited for use in routine diagnostics, CUPLR reports the top contributing features and their values compared to cohort averages. The comprehensive output of CUPLR is complementary to existing histopathological procedures and may thus improve diagnostics for patients with CUP. CUP is the first reimbursed indication for WGS in The Netherlands. We will report on the prospective use and clinical utility of WGS for CUP patients in routine diagnostics but also highlight the added value of CUPLR for unsolved differential diagnosis cases and incidental cases where the independent WGS analysis was discrepant with the original tumor diagnosis. Citation Format: Luan Nguyen, Luuk Schipper, Paul Roepman, Kim Monkhorst, Arne van Hoeck, Petur Snaebjornsson, Edwin Cuppen. Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2167.

Merkel cell carcinoma: A systematic review of the demographic and clinical characteristics of 847 cases in Japan.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin associated with Merkel cell polyomavirus and immunosuppression. Although MCC incidence is rising worldwide, MCC has not been sufficiently investigated in Japan. This study aimed to determine MCC demographics in Japan, including incidence, age, sex, location, spontaneous regression, and pure/combined MCC. Using PubMed and Igaku Chuo Zasshi, 847 MCC cases between 1985 and 2015 were extracted, and the main epidemiological characteristics were described. The mean age of all patients was 77.5years. Regarding the characterized lesions, 63.0% were located on the head and neck, 5.2% on the trunk, 12.6% on the upper limb, 15.1% on the lower limb, 3.5% on the buttocks, and 0.6% on the genitals. Histopathological information regarding the presence of other malignancies could be retrieved in 611 cases, and a coexisting malignancy, mainly squamous cell carcinoma and Bowen's disease, was present in 14.2%. Subcutaneous MCC was observed in 31 patients with a male:female ratio of 1.07 (16 men/15 women). Nodal lesions with unknown primary tumor location were described in 19 patients with a male:female ratio of 0.9 (nine men/10 women) and a mean age of 77.7years. Of 640 evaluable cases, spontaneous regression developed in 9.1%. Among those 58 patients, the male:female ratio was 1:2.1 in 56 evaluable cases (18 men/38 women). Merkel cell polyomavirus was assessed in 180 patients, and the virus was detected in 31.1% and not detected in 68.9% of the patients. MCC is a rare disease in Japan, with incidence rates and male:female ratios differing from those in the USA and European countries. Besides, this study reveals the high frequency of subcutaneous MCC and MCC with divergent differentiation patterns and spontaneous regression in Japan compared to other countries.

Undifferentiated cancer with unknown primary location infiltrating the rectum – a case report

Colorectal cancer (CRC) is the third leading malignancy in men after prostate and lung cancer. Adenocarcinomas account for about 90% of all colorectal cancer cases. Carcinomas of unknown primary site (CUPs) are usually found in patients &gt; 60 years of age. They account for 3% of all malignancies in Poland. We describe a diagnostically challenging case of undifferentiated carcinoma of unknown primary site invading the rectum. Rectal specimens collected during endoscopy and open biopsy, as well as samples collected during laparotomy from the side of the peritoneal cavity did not confirm cancer despite progressing clinical symptoms of an ongoing neoplastic process. Histopathological diagnosis was obtained only with core-needle biopsy of the rectal infiltration and sphincter muscles. The histopathological confirmation of carcinoma invading the sigmoid colon, rectum, anus and the mesorectum described in PET-CT enabled patient qualification for further palliative treatment.

Morphometric and immunohistochemical features of TTF-1 positive lung tumors: improvement of approaches to the diagnosis of unknown primary sites metastases

Verification of lung tumors in the practical activity of a pathomorphologist reached a completely different level due to the use of additional highly sensitive diagnostic methods (immunohistochemical (IHC) and cytogenetic studies). Thyroid transcription factor 1 (TTF-1) plays a key role in lung morphogenesis and is expressed in about 90 % of pulmonary small cell carcinomas. The positivity of TTF-1 in pulmonary and extrapulmonary neuroendocrine tumors is actively debated in the literature, therefore, the results of IHС on TTF-1 in metastases from an unknown source should be interpreted carefully and constantly improve differential diagnostic algorithms, expanding IHC panels with organ-specific markers, and focus on additional morphometric indicators research of nuclei of tumor cells.The aim of the work is to investigate the complex of morphological, morphometric, and IHC characteristics of TTF-1 positive lung tumors to improve the diagnostic algorithms for metastases from an unknown primary source.Materials and methods. A retrospective analysis of histological, morphometric and IHC characteristics of the biopsy material TTF-1 of positive lung carcinomas from 36 patients (10 women and 26 men) aged 29 to 81 years (mean 58.03±10.83 years) for the period 2015–2018, taken from the archive of the morphological department of the medical-diagnostic center of LLC “Pharmacies of the Medical Academy” (Ukraine, Dnipro).Results. In the diagnosis of carcinomas of unknown primary localization with suspected lung origin, it is necessary to take into account morphological, morphometric and IHC features together, which is associated with the similarity of metastases of squamous cell carcinomas of the head and neck, mucinous adenocarcinomas of the gastrointestinal tract and neuroendocrine carcinomas from Merkel cells corresponding to the histological forms lung tumors, as well as insufficient sensitivity of the marker TTF-1.Conclusions. Use of the minimum primary (Cytokeratin, Pan AE1 / AE3 (+) / Vimentin (- / +) / CD45 (-) / S100 (- / +)) and secondary (Ck 7 +, Ck 20 -, TTF-1 + ) IHC panels will prove that the phenotype of carcinoma of unknown primary site corresponds to the form of disseminated lung carcinoma, and additional markers Сk HMW, p63, Chromogranin A, Synaptofisin and / or CD56 together with morphometric indices of the nuclei will determine the histological form of lung carcinoma with justification for the use of appropriate therapy

Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients’ prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients’ samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.

DIAGNOSIS OF GERM CELL TUMORS OF EXTRAGONADAL LOCALIZATION IN TERMS OF ALGORITHMS FOR DETECTING METASTASIS OF CARCINOMAS OF UNKNOWN PRIMARY LOCALIZATION

The analysis of cases of extragonadal teratomas makes it clear that tumours derived from germ cells and mainly characteristic of adult gonads can also occur in other areas, such as the anterior mediastinum (thymus) and midline brain (germinomas of the epiphysis and the area above the Turkish saddle), that requires differential diagnosis with metastases of carcinomas of other origin. Accurate diagnosis of estrogenic germ-cell tumours by only routine staining with haematoxylin-eosin requires high expertise and experience due to their non-specific clinical symptoms and variability of morphological characteristics. Tumour morphologists consider that immunohistochemical investigation plays an important role in accurate histological diagnosis of these tumours. The goal of this study is to explore the expression features of immunohistochemical markers and morphometric parameters of the area, perimeter and "roundness" of the nuclei in various types of extragonadal germ-cell tumours compared to similar primary ovarian / testicular tumours in order to improve diagnostic algorithms. A study was conducted on biopsy or postoperative samples taken from 8 patients (group 1) with extragonadal germ-cell tumours and from 16 patients with primary germ cell tumours of testicles / ovaries (group 2). The diagnoses were confirmed by immunohistochemical investigation on the basis of the pathologic department of the “Pharmacy of Medical Academy” Diagnostic Centre for 2015 to 2018. PLAP and CD117 had the highest percentage of expression in seminomas and gerninomas of both studied groups; morphological parameters were 3-fold higher in area and ̴2-fold higher around the perimeter then the values of normal lymphocytes (p&lt;0.05). Expression of markers CD30, EMA and CK AE1/3 was diagnostically significant in samples of embryonic carcinoma, and morphological parameters ̴were ̴ 2.1 times higher in area and ̴ 1.7 along the perimeter that exceeded the values of normal lymphocytes (p&lt;0.05). αFP-positive staining was indicative of yolk sac tumours, which morphological parameters were more than ̴ 1.7 times higher in the area and ̴ 1.5 times higher along the perimeter compared with the normal lymphocytes (p&lt;0.05). Taking into account the variability of morphological characteristics and the possibility of extragonadal location of tumours derived from germ cells, immunohistochemical research supported by morphometry is an important tool in the differential diagnosis of carcinomas of unknown primary localization.

Metastatic bone lesions of men in combination with an increase in serum PSA from the point of view of diagnosing carcinomas of unknown primary localization

In cases of “malignant neoplasm of unknown origin” of men with bone metastases, it is the serum PSA level that can be crucial for further treatment. The literature describes carcinomas with bone metastases and an increase in the prostate-specific antigen, which were twice refuted by a prostate biopsy but had a positive dynamic during anti-androgen therapy (bicalutamide) in combination with chemotherapy (zoledronic acid). The aim of the work is to improve diagnostic algorithms, to investigate a complex of morphological, morphometric and immunohistochemical characteristics of metastatic foci in the bones, which are represented by adenocarcinomas of unknown primary localization in men with increased serological marker PSA, compared with primary carcinomas of the prostate gland. Materials and methods. A retrospective analysis of clinical data, histological and immunohistochemical characteristics of 21 observations of biopsy material from patients with primary carcinoma of the prostate gland (group 1, men aged 56 to 82 years, average 66.00 ± 7.76; median 65) and 10 patients with bone carcinoma metastases without primary localization and increased serum marker PSA (group 2, men aged 43 to 57 years, mean 50.00 ± 9.89; median 46.5) on the basis of the morphological department of diagnostic center “Pharmacy of Medical Academy” for the period 2015–2017. Results. Morphological, morphometric and immunohistochemical changes of carcinomas of unknown primary site in men with metastatic bone lesions and increased serum marker PSA associated with the acquisition of more aggressive properties were identified in comparison with the primary carcinomas of the prostate gland, which tend to local distribution. There were prevalence of poorly differentiated histological forms of metastatic adenocarcinomas, an objective reduction in the area and perimeter of nuclei (P = 0.00002, P < 0.0001, respectively), possible loss of immunohistochemical markers AMACR (p504s) and AR (androgen receptors) specific for acinar prostate carcinomas (P = 0.008). Conclusion. The use of minimal primary immunohistochemical panel from cytokeratin, Pan AE1/AE3 (+) / Vimentin(-) / CD45(-) / S100(-) and secondary – cytokeratin 8(+) / PSA(+) / AMACR (p504s)(+) panels / AR(+/-) will allow to prove the conformity of the carcinoma phenotype with unknown primary site in men with metastatic bone lesions and an increase in the PSA serological marker to the form of disseminated prostate carcinoma with justification for the use of appropriate therapy in cases of non-informative prostate biopsy.

Metastases of Merkel cell carcinoma in terms of diagnosing carcinomas with unknown primary localization.

Merkel cell carcinoma (MCC) is a rare malignant primary skin neoplasia with epithelial and neuroectodermal differentiation. The problem of MCC, which determines the relevance of its research, is often a high frequency of local recurrence, regional lymph node metastasis and further hematogenous and/or distant lymphogenous dissemination. Materials and methods. A retrospective analysis of the biopsy material of 6 patients with isolated MCC metastasis aged from 29 to 82 years (average 63.11 ± 16.24; median 62.5) was carried out. For the control group, 9 cases of postoperative material of primary skin tumors with MCC of patients aged from 27 to 76 years (average 52.17 ± 12.72; median 53.5) were selected to determine the differential diagnostic criteria. The results of the study. Carcinomas without primary localization may be interpreted as MCC if they demonstrate phenotype Cytokeratin, Pan AE1/AE3 (paranuclearly +) / CK20 (paranuclearly +) / Vimentin (-) / CD45 (-) / S100 (-) / Chromogranin A (+) / Synaptophysin (+), with morphometric parameters of the area and perimeter, which is 2 times the size of ordinary lymphocytes, (all p>0.05). Findings. Metastatic CMC without primary localization, in comparison with locally spreading, often exhibit low-differentiated small-cell and transitional forms, which require additional immunohistochemical study to exclude carcinomas of other origin.

Neuroendocrine tumors from an unknown primary source: immunohistochemical and morphometric features

Neuroendocrine tumors belong to the group of favorable carcinomas of unknown primary location, but 90% of them are poorly differentiated by tumors that require immunohistochemistry to establish histogenesis of cells. The aim is to investigate the complex of morphological, morphometric and immunohistochemical characteristics of cases of neuroendocrine carcinoma without primary localization for improvement of verification algorithms of the primary source. Histological, morphometric and immunohistological characteristics of the biopsy material were established for 107 patients with neuroendocrine tumors without primary localization. The statistical analysis of the parameters of planes, perimeters and the circle coefficient of cells was performed in ImageJ and Microsoft Excel programs with the calculation of minimum, maximum, median (M), arithmetic mean (χ) and standard deviation (SD). The analysis of the distribution of observation groups was carried out according to the t-criterion. The most frequent localization of such neuroendocrine tumors is described in the retroperitoneal region, mediastinum and peripheral lymph nodes (40%), liver (25%) and bones (10–15%). With a decrease in the degree of differentiation of neuroendocrine tumors, the size of cell nuclei and the proliferation index in all studied groups significantly increased (all p &lt;0.05).

Isolated carcinomatosis of the abdominal cavity in women: the features of immunophenotypes and morphometric parameters.

Patients with isolated abdominal carcinomatosis are traditionally treated similarly to patients with ovarian cancer stage III/IV. Despite histological, molecular and clinical similarities, this approach leaves no room for studying the individual biology of this phenotype of cancer of unknown primary localization. In addition, some metastases of gastrointestinal, pancreatic-biliary or endometrial adenocarcinomas simulate the histological and/or immunohistochemical (IHC) characteristics of primary ovarian adenocarcinomas. Over the past three decades, understanding the biology and pathways of intra-abdominal dissemination of tumors, taking into account the protective function of the peritoneal barrier against further tumor spreading, has led many researchers to consider the concept of peritoneal carcinomatosis as a locoregional disease. In the absence of other systemic metastases, new multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermia chemotherapy, and systemic chemotherapy are considered promising for improving disease control and increasing survival. Materials and methods. A retrospective analysis of clinical data, histological and IHC characteristics of biopsy material of 24 women with isolated abdominal carcinomatosis at the age of 28 to 81 years (mean 56.29±14.68, median 58.5) and 46 cases of primary ovarian tumors of women at the age of 27 to 76 years (mean 52.17±12.72, median 53.5), was performed to determine differential diagnostic criteria. IHC profile of primary ovarian tumors determined the most specific markers of cytokeratin C7 and CA125 (mucin 16), which in 43 out of 46 (93.48%) and 37 of 46 (80.43%) were respectively positive at least partially. It should be noted that 1 undifferentiated carcinoma was negative for both markers, only for SC7-2 mucinous adenocarcinomas and 1 low-grade, but only for CA125-2 endometrioid, 2 light-celled, 1 undifferentiated carcinoma and 4 low-grade adenocarcinomas (the latter were regarded as primary in exclusion of other localizations on the basis of a complete survey). Receptors to estrogens were determined in 14 of 46 (30.43%) of observations, which indicates their prognostic, and not diagnostic significance. In the group of women with isolated carcinomatosis of the abdominal cavity, SK7 was identified in 21 of 24 (87.5%) observations, CA125 in 16 of 24 (66.67%), all of whom had SC7 immunoreactivity, but only 9 of them demonstrated the presence of estrogen receptors, and 6 – serous phenotype (WT-1+), and 1 – mesothelioma (CK7 +, calretinin +). It should be noted that CA125-partially positive tumor patterns were often mixed with undifferentiated and nopapillary tumor deposits. These women were older than of the entire subgroup (mean 61.4 ± 10.08, median 61), but without significant difference (p>0.05). Conclusions. Only 2/3 of the investigated cases of carcinomatosis without primary localization in women after IHC research can be convincingly attributed to ovarian metastases for the application of appropriate therapy. Other 33.33% percent in our study were divided into 1 - neuroendocrine cancer (Chromogranin +, Synaptophysin +), 3 - colorectal (CK20 + CDX2 +), 2 - moderately and 1 - low-grade carcinomas with doubtful immunophenotypes (CK20+/-CDX2-/+CK7-/+Vimentin -/+), as well as 1 mesothelioma.

Low Radiation Therapy Dose of Cardiac and Descending Aorta are Associated with the Worst Grade of Radiation-Induced Lymphopenia in Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Circulating lymphocytes are highly sensitive to radiation. Severe lymphopenia (grade 4) is associated with worse clinical outcomes in cancer patients. We sought to identify the association between cardiac dose and lymphopenia grade in non-small cell lung cancer (NSCLC) patients. A total of 138 patients with stage IIb-IV NSCLC were included in this study. They were among those enrolled in a randomized protons vs. IMRT concurrent chemoradiation therapy (CCRT) lung trial. Cardiac regions of interest (ROIs) were automatically delineated using an in-house developed multi-atlas contouring system, followed by manual editing by a thoracic radiation oncologist using the RTOG 1106 atlas contouring guidelines. The cardiac ROIs included pericardium, whole heart muscle, left and right ventricles, left and right atria, and large vessels. The dose-volume parameters was extracted for data analysis. Patient’s complete blood count data were collected, which included baseline, at least weekly during CCRT, and on each follow-up. The absolute lymphocyte counts (ALCs) were extracted and lymphopenia was graded according to CTCAE v 3.0. The equality of group medians was assessed with a nonparametric test with p≤0.05 indicating significance. There were 95 IMRT and 43 PSPT patients. Tumor location were left upper lobe 31, left lower lobe 15, mediastinum 5, right upper lobe 60, right middle lobe 7, right lower lobe 18, and unknown primary tumor location in 2 (Metastatic mediastinal lymph node carcinoma). The worst lymphopenia grade was: 0-2 in 13 (9.4%) patients, grade 3 in 70 (50.7%) patients, and grade 4 in 55 (39.9%) patients. All the cardiac dosimetric parameters were highly correlated with the worst lymphopenia grade. Table 1 shows the relationship between dose-volume indices of some of the cardiac substructures and the worst lymphopenia grade (0-2 vs. 3 vs. 4). Results from this study show that percentages of V5 to V10 for cardiac muscle, pericardium, heart chambers, and descending aorta are significantly associated with the worst grade lymphopenia in locally advanced NSCLC.Tabled 1Abstract TU_35_3667; Table 1The worst lymphopenia grade0-234Median Test p-valueThe worst lymphopenia grade0-234Median Test p-valueCases137055137055Cardiac Muscle V5 (%)223952<0.001Cardiac Muscle V10 (%)173143<0.001Pericardium V5 (%)365060<0.001Pericardium V10 (%)3143520.001Left Ventricle V5 (%)622320.002Left Ventricle V10 (%)313200.001Right Ventricle V5 (%)1228450.005Right Ventricle V10 (%)721370.002Left Atrium V5 (%)3761750.001Left Atrium V10 (%)2951650.001Right Atrium V5 (%)184063<0.001Right Atrium V10 (%)143256<0.001Descending Aorta V5 (%)3859630.001Descending Aorta V10 (%)3250510.006 Open table in a new tab

Carcinomas of unknown primary localization with isolated unilateral lesion of axillary lymph nodes in women.

Серед найбільш важливих досягнень останніх десятиріч у розумінні біології раків невідомої первинної локалізації було виявлення сприятливих клінікопатологічних підгруп (фенотипів), що зустрічаються в 10-20%. Жінки з карциномою молочної залози, що уражує тільки пахвові лімфатичні вузли, являють собою порівняно рідку когорту пацієнтів, які мають перспективи довгострокового виживання. Матеріали і методи. В роботі проведено ретроспективний аналіз характеристик біопсійного матеріалу 29 пацієнток з ураженням ізольованих однобічних пахвових лімфатичних вузлів без відомої первинної локалізації, віком від 32 до 86 років (середнє 61,52±14,42; медіана 60) й 48 спостережень післяопераційного матеріалу пацієнток з первинною пухлиною молочної залози, віком від 30 до 89 років (середнє 55,43±12,19; медіана 56) за період 2015 – 2017 рр. Результати дослідження. Дослідження карцином невідомої первинної локалізації з ураженням ізольованих однобічних пахвових лімфатичних вузлів у жінок виявило значну перевагу Сytokeratin, Рan АЕ1,АЕ3+ / цитокератин 7+/ ER+/ PGR+/ Her-2-new- випадків метастатичних карцином фенотипу молочної залози. Подібно до первинних пухлин молочної залози, метастатичні карциноми мали морфологічну будову і показники площини, периметру та круглості ядер (всі р>0,05), але відрізнялися розподілом фенотипів за комбінацією прогностичних маркерів «золотого стандарту» ER, PGR, Her-2-new (р=0,03746). Висновки. З падінням ступеня диференціювання первинні та метастатичні АК молочної залози можуть набувати «три-негативного» статусу, що з огляду на високі відсотки низькодиференційованих аденокарцином і недиференційованих раків серед спостережень (28% і 10% відповідно), потребує розширення ІГХ панелі органоспецифічними маркерами молочної залози та маркерами виключення.