Large Cell Undifferentiated Carcinoma Research Articles

A case of large-cell undifferentiated carcinoma of the bladder

Abstract Large-cell undifferentiated carcinoma of the urinary bladder is an extremely rare and aggressive neoplasm. We present a unique case of painless gross hematuria and a past surgical history of cystolithotomy. The patient underwent transurethral resection of the bladder tumor, which revealed high-grade urothelial cell carcinoma with lamina propria involvement. Subsequent radical cystoprostatectomy with orthotopic neobladder urinary diversion and pelvic lymphadenectomy was performed, and the postoperative pathologic examination indicated large-cell undifferentiated. This case report highlights the importance of accurate diagnosis and management for this rare malignancy and adds to the limited existing literature on Large-cell undifferentiated carcinoma.

LARGE CELL UNDIFFERENTIATED CARCINOMA OF PAROTID GLAND: A CASE REPORT AND LITERATURE REVIEW

Large cell undifferentiated carcinoma of parotid gland is a rare disease of salivary gland cancer accounting about 1%, however, it has high malignancy and very poor prosgnosis. We report a clinical case with symptoms of left parotid gland tumor, rapid growth , invasive skin and superficial ulceration . The differential diagnosis is difficult between parotid adenocarcinoma and skin cancer or metastatic cervical lymphoma. The patient underwent extensive surgical resection of the lesion, radical cervical lymphadenectomy, and reconstruction with local flaps. The definitive diagnosis after surgery: large cell undifferentiated carcinoma of the left parotid gland stage IV (pT4aN0M0). The patient did not receive early radiation therapy, therefore local recurrence and distal metastasis, and death 6 months after surgery.

Spontaneous Haemothorax and Diffuse Pleural Thickening as Unusual Presentations of Undifferentiated Large Cell Carcinoma of the Lung

Spontaneous Haemothorax and Diffuse Pleural Thickening as Unusual Presentations of Undifferentiated Large Cell Carcinoma of the Lung

CT-Guided FNAC of Lung Lesions and Cytological Sub-Classification of Bronchogenic Carcinoma of 246 cases at a Tertiary Care Hospital

Background: CT-guided fine needle aspiration cytology (FNAC) is a useful tool for evaluating lung nodules or masses. In view of the relative paucity of published studies regionally, this study was undertaken in the Department of Pathology, Enam Medical College & Hospital to see the use of the technique. Materials and Methods: Two forty six CT guided lung FNACs were performed during January 2017 to December 2018 and cytological diagnoses were made. Reported results and relevant data were recorded in the data sheet and then analyzed by standard statistical method. Results: Total number of cases were 246. Adequate samples were obtained in 228 (92.68%) cases, among the adequate samples 135 (59.41%) were malignant, and 93 (40.49%) were benign or nonmalignant lesions. Among the benign lesions, lung abscess (36;38.70%) was the most common followed by pulmonary TB (27;29.03%). Adenocarcinoma (54;40%) was the most common type of bronchogenic carcinoma followed by squamous cell carcinoma (51;37.78%), small cell carcinoma (21;15.56%), NHL (6;4.44%) and large cell undifferentiated carcinoma (3;2.22%). In male persons, squamous cell carcinoma (42.85%) was the most common type of bronchogenic carcinoma, followed by adenocarcinoma (34.29%). In female, adenocarcinoma was the most common type (18;60%) of bronchogenic carcinoma, followed by squamous cell carcinoma (6;20%). Conclusion: FNAC is a safe method for the evaluation of lung nodules and it enables sub-classification of bronchogenic carcinoma in the vast majority of cases. It is also useful for the diagnosis of tuberculous pulmonary nodules. J Enam Med Col 2020; 10(3): 169-173

Prognostic Factors and Survival of Patients with Primitive Lung Cancer in Douala and Yaounde

Background: Primary lung cancer (PLC) represents a real public health problem. It is one of the main types of cancer in the world in terms of incidence and also the main cause of death from cancer. In Africa primary bronchial cancer appears to be a rare entity. Objective: To study the prognostic factors and survival of patients with PLC in Douala and Yaounde. Patients and method: We performed an analytical, longitudinal (retrospective) study over a period from January 2010 to December 2019 including all records of patients in whom the diagnosis of PBC was histologically proven. The data collected were recorded and analyzed by SPSS version 25. Survival was determined by the Kaplan Meier method and the search for prognostic factors was carried out using the Cox proportional hazards model. A value less than 0.05 were considered significant. Results: A total of 94 patients were included in the study. The sex ratio was 1.24. The median age at cancer diagnosis was 62 years old. More than half of the population (61 cases; 64.9%) resided in urban areas; 51 (54.3%) were exposed to tobacco, 14 (14.9%) had occupational exposure and 88.1% of women were exposed to biomass smoke. The average smoking index was 29.24 ± 26.27 pack-years and the average duration of exposure was 30.17 ± 4.36 years. The histological types encountered were in order of decreasing frequency: adenocarcinoma (48 cases; 51.1%), squamous cell carcinoma (33 cases; 35.1%), small cell lung cancer (8 cases; 8.5 %) and undifferentiated large cell carcinoma (5 cases 5.3%); in the majority of cases the cancer was diagnosed at stage IV for non-small cell lung cancer (62 out of 86 cases) and at the localized stage for small cell lung cancer (6 out of 8). Of the 94 cases collected, 56 (59.6%) had adhered to anti-tumor treatment. The median overall survival was 4 months with 95% CI [1.52-6.79]. The overall survival rates at 6 months, 12 months, 24 months and 36 months were 50%, 17.4%; 12% and 8.7% respectively. The poor prognostic factor found was: The presence of brain metastases (HR: 80.01; p-value: 0.004). Conclusions: Survival was very low with a median overall survival of 4 months. The overall survival rates at 6 months, 12 months, 24 months and 36 months were 50%, 17.4%, 12% and 8.7% respectively. The poor prognostic factor found was: the presence of brain metastases.

A case report of large cell undifferentiated carcinoma of the urinary bladder

The clinical pathological data of a patient large cell undifferentiated bladder carcinoma was retrospectively analyzed and understand. The clinical and imaging findings of large cell undifferentiated bladder carcinoma was nonspecific. Diagnosis depended on the pathological and immuno-histochemical staining. The tumor is aggressive with high risk of recurrence.It is mainly treated with radical resection. Key words: Urinary bladder; Undifferentiated carcinoma; Large cell carcinoma

P1.10-06 Pathological Characterization of Radon-Induced Lung Cancer in Rats

Radon is a radioactive gas, considered the leading cause of lung cancer in non-smokers. Although the risk of lung cancer is linear, there is no safe level and even low dose can be associated with risk. In humans, no specific pathological subtypes of lung cancer have been clearly associated with radon. In animals, the French Atomic Energy Commission (CEA) exposed to low dose of radon (25 working level month, WLM) a large cohort of rats in a radon-exposure chamber, showing lung cancer induced by low exposure (Chameaud J, Radiation Prot Dosimetry 1984). We aimed to describe pathological features of radon-induced tumors in rats from the CEA’s cohort. Retrospective assessment of archival samples available of the rats exposed to low-dose radon in the Laboratoire de Pathologie Pulmonaire Experimentale, COGEMA (France), between 1989 and 1992. Autopsy reports were also reviewed. The pathological assessment was performed for a thoracic oncology pathologist (JA) in H&E staining slides according to the current WHO histological classification. Samples from 117 rats were collected. Among 104 tumors, to date the analysis has been performed in 94. Forty tumors (43%) were classified as malignant, 28 (30%) as uncertain malignant potential (UMP) and 26 (28%) benign. In 2 rats (2%) synchronous malignant and non-malignant tumors were observed. Among the malignant tumors, 23 (58%) were epithelial and 17 (42%) non-epithelial. Lung carcinoma was the most common primary epithelial tumor (n=10, 43%), followed by abdominal area tumors (n=5, 22%), and thyroid (n=3, 13%). In the UMP group, 7 (25%) were epithelial and 21 (75%) non-epithelial, with no lung tumors observed. In the benign group, most of them (n=24, 92%) were epithelial, with 4 cases with lung atypical adenomatous hyperplasia-like lesions; 2 synchronous with other malignant tumors (n=1 lymphoma, n=1 cutaneous squamous cell carcinoma). A total of 26 tumors (27%) had thoracic involvement: 4 (15%) primary lung non-malignant lesions, 11 primary lung malignancies (42%) and 11 with metastases from other tumors (42%). As primary malignant lung tumors, we observed: 7 (64%) adenocarcinoma in situ, one papillary adenocarcinoma, one undifferentiated large cell carcinoma with bilateral metastases, one metastatic squamous carcinoma and one metastatic undifferentiated tumor, compatible with sarcoma In this cohort of radon-induced tumors in rats, we observed different tumor types, from non-malignant lesions to aggressive malignancies, with predominance of epithelial tumors. Lung carcinoma was the most common primary tumor and adenocarcinoma the histological subtype more observed, with histological similarities with humans.

Features of the expression of prognostic markers p16, Her2 / new and changes in the corresponding genes in individual phenotypes of cancers of unknown primary origin.

Background. Approximately 2/3 of cancers of unknown primary origin (CUP) are adenocarcinomas with mucin production, the formation of gland-like structures and immunohistochemistry results that can determine the histological subtype, but cannot determine the exact primary place of origin. The remaining 1/3 of CUP is a mixture of non-adenocarcinomas, including squamous cell carcinomas, neuroendocrine carcinomas, small-cell and large-cell undifferentiated carcinomas. Objective. In such cases, molecular profile identification and gene sequencing may be a promising approach to the classification and direct treatment of CUP. Methods. A retrospective analysis of biopsy or postoperative material of 61 patients (34 women and 27 men) aged 26 to 74 years (mean 53.4 ± 11.42; median 52) with an initial diagnosis of CUP was performed. Immunohistochemical studies were carried out according to the protocols of TermoScientific (USA) with antibodies to p16INK4a and HER2/neu. Fluorescence in situ hybridization was performed according to the protocol of ZytoVision GmbH (Germany). Changes in the ERBB2 and CDKN2A genes were evaluated for gene amplification and deletion of the 9p21 locus, respectively, with double-labeled DNA probes. Results. Of the 61 studied cases of CUP, p16 expression was positive in 31 cases (51%), the basis for which was 9 homozygous and 19 heterozygous 9p21 deletions, which were found in all but one of the studied CUP phenotypes. HER2 / neu expression was positive (2 + / 3 +) in 15 of 61 (25%) CUP, but only in 9 of them had actual amplification of the ERBB2 gene on FISH in 5 phenotypes. Conclusion. The reduced number of phenotypes with amplification of the ERBB2 gene makes it more specific for the differential diagnosis of CUP, compared with the deletion of 9p21 (p16 / CDKN2A), which is likely to be universal in acquiring an aggressive course of carcinomas of various localizations.

Correlation analysis of expression and prognosis of TTF-1 and CD44v6 in undifferentiated lung carcinoma.

The correlation between expression and prognosis of thyroid transcription factor-1 (TTF-1) and CD44v6 in undifferentiated lung carcinoma was investigated. There were 116 cases with large cell undifferentiated carcinoma in group A, 120 cases with small cell undifferentiated carcinoma in group B and 80 normal individuals from the same period in group C. The expression levels of TTF-1 and CD44v6 in the serum of group A, B and C and the cancer tissues and adjacent tissues of group A, B and C were detected using enzyme-linked immunosorbent assay (ELISA), and the levels in each group were compared. Pearsons test was used to analyze the correlation between TTF-1 and CD44v6 expression in serum of group A and group B and cancer tissues. Patients were divided into the survival group and the deceased group according to their 5-year survival. Multivariate logistic regression was applied to analyze the risk factors of mortality, and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of TTF-1 and CD44v6. The best cut-off values of TTF-1 and CD44v6 were divided into the high and low expression groups to observe the 5-year mortality of patients and the Kaplan-Meier (K-M) survival curve was drawn. Multivariate logistic regression was used to analyze the risk factors of mortality. The expression of CD44v6 in the serum of group A and group B was higher than that in group C, and that of group B was higher than that in group A (P<0.05). The expression of TTF-1 in serum of group A and group B was higher than that of group C, and the expression of TTF-1 in group A was higher than that in group B (P<0.05). The expression of TTF-1 and CD44v6 in group A and group B were significantly higher than those in adjacent tissues (P<0.05). The expression of TTF-1 in group A was higher than that in group B (P<0.05), and that of CD44v6 was lower than that in group B (P<0.05). The 5-year survival of patients showed that 209 patients died and 27 survived at 5 years; the survival rate was 11.44%. The course of disease, TNM stage, TTF-1 and CD44v6 were independent mortality factors for undifferentiated lung cancer.

Concordance levels of PD-L1 expression by immunohistochemistry, mRNA in situ hybridization, and outcome in lung carcinomas

Targeted inhibition of programmed cell death-1 (PD-1) and its ligand (PD-L1) has emerged as first-line therapy for advanced non-small cell lung cancer. Although patients with high PD-L1 expression have improved outcomes with anti-PD-1/PD-L1-directed therapies, use as a predictive biomarker is complicated by robust responses in some patients with low-level expression. Furthermore, reported PD-L1 levels in lung cancers vary widely, and discrepancies exist with different antibodies. PD-L1 expression was thus compared by immunohistochemistry (IHC) versus RNA in situ hybridization (ISH) in 112 lung cancers by tissue microarray: 51 adenocarcinoma, 42 squamous cell carcinoma, 9 adenosquamous carcinoma, 5 carcinoid, 3 undifferentiated large cell carcinoma, 1 large cell neuroendocrine carcinoma, and 1 small cell carcinoma. At least 1% tumor cell staining was considered positive in each modality. A positive concordance of only 60% (67/112) was found between IHC and ISH. Fifty percent (56/112) were positive by IHC and 50% (56/112) by ISH; however, 20% (22/112) were ISH positive but IHC negative. Conversely, 21% (23/112) were IHC positive but ISH negative. There was no significant stratification of PD-L1 positivity by histologic subtype. A trend of more PD-L1-positive stage I cancers identified by ISH versus IHC was observed but was not statistically significant (50% [27/54] by IHC and 64% [35/55] by ISH, P = .18). No significant difference in survival was identified, with an average of 5.3 months in IHC versus 5.2 months in ISH-positive cases. The results demonstrate discordance between PD-L1 RNA levels and protein expression in non-small cell lung cancers, warranting comparison as predictive biomarkers.

Primary large cell neuroendocrine carcinoma of the skin: An under‐recognized entity and a mimic of metastatic disease

Primary large cell neuroendocrine carcinomas of the skin are exceptionally rare and can be diagnosed only when a metastasis from another organ has been excluded. We report the case of a 62-year-old woman with a cutaneous papule on the mid-chest which generated a differential diagnosis of vascular lesion and basal cell carcinoma. Following excision, microscopic evaluation revealed a dermal large cell undifferentiated carcinoma, with a brisk mitotic rate and focal geographic necrosis. Mucin production was absent. On immunohistochemistry, the lesion expressed CK7, AE1AE3, CK8/18, chromogranin, synaptophysin, CD56, calcitonin (patchy) and TTF-1 (minimal focal). Stains for neurofilament, CK20, CK5/6, p40, p63, SOX10, MART-1, EMA, CEA, ER/PR, GATA3, GCDFP, mammoglobin, PAX-8, CDX2, napsin, ERG and MCPyV proved negative. The histopathological diagnosis was of a large cell neuroendocrine carcinoma, probably metastatic. The patient underwent comprehensive clinical, laboratory and radiographic investigations and no underlying primary carcinoma was detected. During a 20-month follow-up period with an oncologist, the patient remains well and free of any apparent carcinoma. This suggests a primary large cell neuroendocrine carcinoma of skin. To date, 3 such cases have been reported in Japanese patients. This is the first in a Caucasian resident of North America.

Chest X-ray of lung cancer: Association with pathological subtypes

Background: Chest radiography is an essential initial investigation for the suspected cases of bronchogenic carcinoma and can be a predictor of malignancy. Aims: To assess the radiographic presentation and distribution of the different pathological cell types of lung cancer in our hospital. Materials and Methods: A total of 125 consecutive suspected patients with lung cancer, who had initial chest X-ray lesions suspicious of malignancy (mass lesion, nodules, pleural effusion, evidence of bronchial obstruction such as collapse, unresolved consolidation, etc.), were selected as the study population. The contrast-enhanced computed tomography (CT) scan of the thorax, CT-guided fine-needle aspiration cytology, fiberoptic bronchoscopy and Tru-cut biopsy were performed in the patients as feasible to find out the pathological cell type of bronchogenic carcinoma. Then, the chest X-rays were clinically correlated in all the lung cancer cases. In addition, the relationship of chest X-ray with the pathological cell types was assessed in the cases of lung cancer. The data were presented and analysed by the standard statistical method. Results: In our study, squamous cell carcinoma was the predominant cell type (47.12%) followed by adenocarcinoma (29.81%). Squamous cell carcinoma and small cell carcinoma commonly presented as central lesions, whereas adenocarcinoma and large cell carcinoma manifested most frequently as peripheral lesions. The common radiographic presentation of squamous cell carcinoma was collapse (38.78%) followed by unresolved consolidations (28.57%) and masses, whereas adenocarcinoma mostly presented as nodules (38.71%) followed by pleural effusion (29.03%). Small cell carcinoma, large cell carcinoma and undifferentiated carcinoma mostly manifested as mass lesion on chest radiography. Conclusion: Chest roentgenography can provide a clue about the pathological cell types of bronchogenic carcinoma, especially in the cases of hilar or parahilar lesions, collapse, non-resolving consolidations and effusions.

PUB021 Sonographic Echo-Pattern of Various Lung Carcinomas among the Cytology Positive Patients

Over the last decades, due to the widespread availability, low financial cost, non-invasivity and a zero ionizing radiation effect, ultrasound is used as the leading medical imaging modality for the initial diagnostic work-up of various multi-organ medical disorders including lung related pathologies like pleural effusion, lung growths etc. And its basic display mode (which is called the brightness mode) reflects different degrees of echogenicity, depending upon the study organs, areas and their underlying pathologies. It can also be done either as trans-wall or endo-luminal means along with the capability of vascular blood flow study. While low dose computed tomography is used presently as the screening test among the high-risk population groups for lung cancer detection, ultrasonography (as a stand-alone modality or as the part of hybrid imaging technique) can be used as a convenient guide for the collection of small biopsies from which efficient interpretation regarding cytological classification and molecular typing are performed as state of the art technology. This study was conducted at the Institute of Nuclear medicine and Allied Sciences, Rajshahi, Bangladesh during the period between 1st May, 2009 and 31st October, 2010. The patients having positive lung lesions on digital radiography are referred at this Institute by the clinicians for ultrasonography of chest and transthoracic ultrasonography-guided fine-needle aspiration biopsy (FNAB) cytological examination, with the co-operation of pathology department of Rajshahi Medical College, Rajshahi, Bangladesh. Under the basis of convenient sampling technique, 77 patients are included as sample. Their age, gender, sonographic echo-patterns of lung carcinomas and cytological findings are recorded and analyzed with statistical software IBM SPSS v. 16. Among the sample (n=77), 67 (87 %) were male and 10 (13 %) were female. Mean (± SD) age was 56 ± 14 years (range=28 to 85 years). Regarding the cytological findings, 30 (39 %) had squamous cell carcinoma, 18 (23.4 %) had undifferentiated large cell carcinoma and 17 (22.1%) had undifferentiated malignant epithelial tumor. And, in relation to the sonographic echo-pattern underlying a single cytology based lung carcinoma among this study sample (n=77), multiple echo-patterns or heterogeneous patterns are noted. The results of this study will be helpful toward the relevant studies which are related to the management algorithm of lung carcinomas, in addition to the role of hybrid imaging techniques as well as histologic classification, molecular typing, genetic and epigenetic profiling from the resected or imaging technique-guided taken small biopsies and cytology specimens.

Predictors of outcomes in large cell undifferentiated carcinoma of the major salivary glands.

Major salivary gland large-cell undifferentiated carcinoma (LCUC) is rare and has a poor prognosis. Characterization of patient demographics, tumor characteristics, and predictors of outcome have been limited by low case numbers, as well as grouped analysis with other salivary malignancies. The objective of this study was to address these issues using large-scale national data. Retrospective case series. Data from the National Cancer Database, including cases diagnosed from 1998 to 2012, was analyzed, identifying 247 records of LCUC. Tumor, demographic, and survival information was extracted and analyzed retrospectively. Large-cell undifferentiated carcinoma comprised < 1% of all major salivary gland cancers. Seventy percent of patients presented with advanced-stage disease. The incidence of occult nodal disease was 39%. Surgery followed by radiation was the most common treatment. Five-year overall survival was 36%. Comorbidity, distant metastasis, and positive surgical margins were found to be predictors of overall survival. To our knowledge, this represents the largest reported case series of LCUC. The survival analysis demonstrates poorer survival in patients with positive surgical margins; therefore, efforts to complete resection are reasonable. Reported high rates of occult nodal disease also strongly support elective treatment of the neck. 4. Laryngoscope, 2016 127:372-376, 2017.

Predictors of Survival in Large Cell Undifferentiated Carcinoma of the Major Salivary Glands

Predictors of Survival in Large Cell Undifferentiated Carcinoma of the Major Salivary Glands

Dissecting Pulmonary Large-Cell Carcinoma by Targeted Next Generation Sequencing of Several Cancer Genes Pushes Genotypic-Phenotypic Correlations to Emerge

Little is known about genotypic and phenotypic correlations in undifferentiated large-cell carcinoma (LCC) of the lung. Thirty LCC were dissected by unsupervised targeted next generation sequencing analysis for 50 cancer-associated oncogenes and tumor suppressor genes. Cell differentiation lineages were unveiled by using thyroid transcription factor-1 (TTF1) for adenocarcinoma (ADC) and p40 for squamous cell carcinoma (SQC), dichotomizing immunohistochemistry (IHC) results for TTF1 as negative or positive (whatever its extent) and for p40 as negative, positive, or focal (if <10% of reactive tumor cells). Three LCC were wild type (all TTF1+/p40-), whereas the remaining 27 (90%) tumors had at least one gene mutation. Twenty-four cases featuring TTF1+/p40-, TTF1+/p40±, TTF1-/p40±, or TTF1-/p40- phenotypes comprised ATM, BRAF, CDKN2A, EGFR, ERBB4, FBXW7, FLT3, KRAS, NRAS, PIK3CA, PTPN11, RET, SMAD4, SMO, STK11, or TP53 mutations in keeping with ADC lineage, whereas three tumors showing TTF1-/p40+ phenotype harbored TP53 only and no ADC-related mutations in keeping with SQC lineage. Single, double, triple, quadruple, and quintuple mutations occurred in 16, 6, 2, 2, and 1 patient, respectively. The occurrence of three mutations or more but not any immunohistochemistry categorization predicted shorter overall survival (OS, p = 0.001) and disease-free survival (DFS, p = 0.007), independent of age, sex, and tumor stage. Albeit preliminary also because of the relatively small number of LCC under evaluation, this targeted next generation sequencing study, however, revealed gene mutation heterogeneity in LCC with some genotypic-phenotypic correlations. Negativity or focal occurrence of p40 made SQC diagnosis unlikely on molecular grounds, but suggested ADC confirming validity of the axiom "no p40, no squamous."

Pattern of treatment and clinico-epidemiological analysis of 804 lung and pleura cancer patients treated in radiation oncology department, NCI-Egypt

BackgroundEpidemiological profile and treatment outcomes of Lung and pleural malignancies vary among different geographical regions. The aim of the study is to analyze the clinico-pathological profile and pattern of treatment of lung and pleural cancers at the Radiation Oncology department, NCI, Cairo University. Materials and methodsA review of 804 clinical patient records with 770 pathologically/cytologically confirmed patients from Jan 2008-December 2012 was performed. Patients were evaluated (clinical, demographic and pathological profiles) in addition to the treatment adopted. ResultsMedian age was 56years with a male: female ratio of 4:1. Smoking was reported in 63% of patients. Dyspnea and chest pain were the most presenting symptoms (53%). Among lung cancer patients; 78% were NSCLC and 12% SCLC with mesothelioma comprising 10%. Among NSCLCs, adenocarcinoma and large cell undifferentiated carcinoma were the commonest histological subtype (72%). Among NSCLC, 58% cases were of stage IV while among SCLC 73% cases had extensive stage disease. Chemotherapy was administered to 47% (55% vs. 67%, and 35% vs. 31% among non-metastatic lung cancer, mesothelioma patients and metastatic lung cancer and mesothelioma patients respectively). Distant metastases (brain 48%, bone 36%) were reported in 45% of patients. The pattern of treatment intent was palliative (88%) vs. 12% treated with radical intent. ConclusionsAdvanced stages at presentation reflect the palliative pattern of treatment. Hypo-fractionated radiotherapy for lung and pleura malignancies as a palliative measure is the current practice. Implementation of early palliative care should be considered for metastatic patients.

Restoration of Patency to Central Airways Occluded by Malignant Endobronchial Tumors Using Intratumoral Injection of Cisplatin.

Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction. We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted. Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD, 64.4 ± 9.5 yr) were treated with one to four injections of 40 mg of cisplatin mixed in 40 ml of 0.9% NaCl. Treatments were completed 1 week apart. The primary etiologies of airway obstruction included squamous cell carcinoma (n = 11), adenocarcinoma (n = 6), small cell carcinoma (n = 2), large cell undifferentiated carcinoma (n = 1), and metastatic endobronchial cancer (n = 2). Twenty-one of 22 patients were evaluable for response. The majority of patients (15/21, 71.4%) responded to therapy, defined as greater than 50% relative reduction in obstruction from baseline. Treatment response was obtained regardless of tumor histology, concurrent systemic therapy, number of treatment cycles administered, performance status, or use of additional ablative interventions. Responders had significantly improved overall survival as compared with nonresponders, although the difference was small. Severe treatment-related side effects or complications were not observed. Subject to the limitations of a single-center retrospective study and a subjective primary outcome measure, we have demonstrated the feasibility of improving the patency of central airways that are largely or completely occluded by endobronchial malignant tumor using intraluminal injection of cisplatin. Additional longer-term, larger-scale safety and comparative effectiveness studies of this palliative treatment modality are warranted.

Giant cell carcinoma of lung with aberrant cytoplasmic localization of p63 protein

Giant Cell Carcinoma is a rare, aggressive type of lung malignancy and very few cases have been extensively studied and reported to date. Because of its rare occurrence, this neoplasm is often not included in the classifications of usual lung cancers. It is considered by some as a variant of undifferentiated large cell carcinoma. Giant cells have, however, been found to occur in different types of lung cancers and their presence in any histologic type is associated with a significantly worse outcome. We present a non-smoking female who was diagnosed with lung adenocarcinoma composed of many giant cells showing cytoplasmic expression of p63 protein. Admitting imaging studies revealed metastases to liver, lymph nodes and the pelvic region. Due to the rarity of this cancer, the diagnosis as well as therapeutic and prognostic features of giant cell carcinoma is often overlooked. This neoplasm has been shown to have dismal response to chemotherapy when compared to other non-small cell lung carcinomas. Cytoplasmic localization of p63, only rarely described, is also associated with poor patient survival.

Pancreaticobiliary tract cytology: Journey toward "Bethesda" style guidelines from the Papanicolaou Society of Cytopathology.

The current series of articles related to the Papanicolaou Society of Cytopathology (PSC) guidelines for pancreaticobiliary cytology are the product of significant efforts by many experts working on different PSC guidelines committees.[1] The PSC guidelines for cytologic interpretation and reporting of variety of body site specimens have been described previously.[2,3,4,5,6] These are comparable to the guidelines from the National Cancer Institute for cervical cytology[7] and fine needle aspiration cytology of breast and thyroid.[8,9] Most of these systems are designed to stratify the risk of malignancy with diagnostic categories for guiding appropriate management algorithms. The current guidelines[10,11,12,13,14] follow the strategies comparable to the Bethesda System for Reporting Thyroid Cytopathology. The guidelines not only consider diagnostic categories and criteria, but also attempt to provide details on other aspects including techniques for obtaining specimens, which patient would benefit most from cytologic evaluation, information on ancillary testing, and patient follow-up/management. The scheme addresses the wide spectrum of approaches to acquire diagnostic material for cytopathologic evaluation from a variety of pancreaticobiliary lesions. A six-tiered system is recommended for the standardized nomenclature in pancreaticobiliary cytology. The categories proposed are: Non-diagnostic, negative, atypical, neoplastic (benign or other), suspicious, and positive.[12] “Atypical” and “suspicious” categories have relatively well reported malignancy risks.[15,16] Potentially, the most challenging and controversial category is “neoplastic (benign and other)” with the widest range of interpretations. The entities included in this category range from innocuous lesions such as benign cystic neoplasms (serous cystadenoma) to others like pre-malignant mucinous cysts (cystic mucinous neoplasm and intraductal papillary mucinous neoplasm), low-grade well-differentiated neuroendocrine tumors (NETs), and solid-pseudopapillary neoplasms. The premalignant mucinous cysts without unequivocal features of malignancy would fall in this category with very wide management options.[17] The NETs similarly have many challenges with controversies related to their categorical assignment. Due to their malignant potential, some favor these neoplasms be categorized as “malignant.” European Neuroendocrine Tumor Society (ENETS) and World Health Organization categorize low and intermediate grades of these as “tumor” or “neoplasm” in the absence of high-grade criteria (>50 mitoses per 50 high power field for NETs of pancreas and >20 mitoses per 10 high power field or Ki-67 index >20% for NETs of other sites).[18,19] Undoubtedly, the lesions with unequivocal cytological features of either small cell carcinoma or large cell undifferentiated carcinoma belong to the “malignant” category. An increasing trend with incidental NETs in surgically unfit older patients, favors a conservative approach for small NETs as an alternative management strategy. The categories proposed in the current guidelines permit practical flexibility by surgeons in order to assure that conservative strategies may be a better option than the surgery. This would be more confusing if these cases of low grade neoplasms automatically fell in a “malignant” category! Utilization of ancillary testing including molecular testing in cystic lesions is also addressed in appropriate areas.[13] With input from the guidelines by the National Cancer Center Network (www.nccn.org) and by the multidisciplinary international groups in the field of pancreatology, post cytologic evaluation and management are also covered.[14] A “triple test” approach similar to that applied for FNA of breast lesions is recommended. Patient management should be determined by correlating the clinical findings in concert with endoscopic, imaging, and cytologic findings. Effective application of such guidelines is heavily dependent on the collaborative, multidisciplinary interactions between endoscopists, pancreaticobiliary surgeons, radiologists, and cytopathologists. The current CytoJournal supplement issue with individual articles[10,11,12,13,14] covering various areas highlighted above would be a great resource under Open access platform[20,21] for all involved in the management of pancreaticobiliary lesions. These PSC guideline articles published under Open Access charter may be disseminated by multiple journals/platforms[22,23,24,25,26] including e-CytoJournal issue http://www.cytojournal.com/browse.asp?sabs=n.[27]