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P3.01-010 Primary Giant Cell Carcinomas of the Lung: Study of Seven Cases
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sectioning was recently described and termed Spreading Through A Knife Surface (STAKS). The purpose of this study was to prospectively examine lung resection specimens for the presence and frequency of STAKS. Methods: A prospective, multi-institutional study of NSCLC lobectomy and pneumonectomy resection specimen was performed from January 1 eJuly 1, 2016. Prosection, sampling and scoring of displaced fragments was undertaken in a systematic manner. The first cut was made with a clean long knife, the second cut was made in a parallel plane to the first cut, without cleaning the knife. Four tissue blocks were sampled: Block 1: first cut, upper part; Block 2: first cut, lower part; Block 3: second cut, upper part; Block 4: second cut, lower part. From these formalin fixed and paraffin embedded tissue blocks a superficial complete H&E stained slide was examined for the presence of displaced tissue fragments at 10 or 20. A displaced fragment was scored as STAKS if the tissue fragment was at least 0.5 mm from the tumor or if it was on the pleural surface in the plane of the second cut. Benign and malignant STAKS were separately noted. Results: A total of 41 resection specimen were included in this study. The mean number of malignant STAKS for blocks 1-4 was 0.36, 1.44, 1.86 and 1.95, respectively and for benign STAKS the mean number was 0.11, 0.11, 0.13 and 0.25, respectively. Almost all STAKS were intraalveolar. Comparison of malignant STAKS in block 1 (before the tumor was reached) with blocks 2-4 (containing tumor) was significant with p-values (p¼0.003 Friedman’s test and post-hoc comparisons p¼0.031, p¼0.002 and p¼0.005, respectively). For benign STAKS no difference was identified (p¼0.23). The chance of malignant STAKS seemed to be higher when tumor was cut fresh than when cut after formalin fixation.
Journal of Thoracic Oncology
Vol. 12 No. 1S
Ana Lopez Gonzalez,3 David Petite Felipe,4 Mariano Provencio Pulla1 1Oncology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/ Spain, 2Pathology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/Spain, 3Oncology, Hospital Universitario de Leon, Leon. Castilla Y Leon./Spain, 4 Radiology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/Spain Background: Giant cell carcinoma (GCC) of the lung is a subtype of sarcomatoid carcinoma (2015 WHO classification) traditionally associated with a highly aggressive clinical behavior. The histology consists in giant cells without differentiated carcinomatous elements. The aim of this study is to analyze the clinical, pathological and molecular features of seven GCC cases diagnosed in our hospital.
Topic: Morphology
Methods: Twenty-nine sarcomatoid carcinoma diagnosed in our hospital during the years 2009-2016 were reviewed and 7 cases with GCC histology were selected for the study. Immunohistochemical staining with antibodies targeting TTF1, napsinA, p40, and b-HCG were performed. ALK and MET status were assessed by FISH. EGFR mutations were performed using real-time PCR. Results: The patients were 4 men and 3 women with a mean age of 61 years (range 45-79). At the moment of diagnosis three patients were current smokers and 4 former smokers. Five cases were peripheral tumors, six in the left lung, and one in the right lung. Complete resection was achieved in all patients. Tumor staging showed 3 cases pT1; 3 with pT2 stage and one case pT3. Histopathologically, all were pure GCC and immunohistochemical stains revealed that the giant cells were negative for b-HCG in all cases except one who could not be analyzed. Two cases showed null phenotype (TTF1 and p40-negative), two cases were TTF1-negative and p40-positive, two cases co-expressed TTF1 and p40 and one case was TTF1-positive and p40-negative. NapsinA was positive in two cases. Molecular analysis was done in 6 cases and no EGFR mutation was detected. FISH results for c-MET probe showed a MET/CEN7 ratio <2 in all cases, polysomy with 5 MET signals without amplification was found in 5 cases. No ALK rearrangement was observed in the series. Five cases showed ALK copy number gain (3 to 5 fusion signals) and one case had two fusion signals. With a median follow-up of 38 months (5-130 months), two patients died due to brain metastases (both with vascular-lymphatic invasion and nodal metastases at the time of surgery), and five patients are alive at the moment of analysis.
Lourdes Gutierrez Sanz,1 Paloma Martin Acosta,2 Clara Salas Anton,2 Ana Isabel Fernandez Diaz,2 Diego Garcia Fresnadillo,2 Fernando Fabio Franco,1
Conclusion: Pure GCC is a very rare lung cancer subtype and there are few series reported. Lymphovascular invasion and lymph node involvement at diagnosis can predict a worse outcome in this subtype. GCC in our
Conclusion: The morphologic definition of STAKS is not different from STAS. This prospective study confirms the presence of benign and malignant STAKS. The presence of malignant STAKS is an artifact and increases with each and every knife cut during tissue sectioning. 1) Thunnissen et al. ArchPatholLabMed2016,140(212-220). Keywords: lung cancer, Pathology, ex-vivo artifacts, false positive diagnosis
P3.01-010 Primary Giant Cell Carcinomas of the Lung: Study of Seven Cases
January 2017
Abstracts
series do not have a specific immunohistochemical profile. Neither EGFR nor ALK were potential molecular targets, nevertheless c-MET status could be an interesting biomarker in GCC tumors. Keywords: Pathology, Giant cell carcinoma, cMET
P3.01-011 Clinocopathological Profile and Role of Immunohistochemistry in the Diagnosis of Primary Lung Cancer - A Prospective Study from Eastern India Topic: Morphology 1
2
Pritinanda Mishra, Susama Patra, Prasanta Mohapatra,3 Mamita Nayak,2 Radhamohan Gharei,2 Manoj Panigrahi,2 Sourin Bhuniya2 1Pathology, All India Institute of Medical Sciences, Bhubaneswar/India, 2All India Institute of Medical Sciences, Bhubaneswar/India, 3Pulmonary Medicine, All India Institute of Medical Sciences, Bhubaneswar/India Background: The clinico-pathological profile of lung cancer has changed considerably over the time in India. The histologic type also has changed from a predominant squamous histology to adenocarcinoma. We performed a prospective evaluation of primary lung cancers (PLCs) on the basis of clinical characteristics, histopathology and immunohistochemistry (IHC). Methods: The clinicohistopathological features and IHC characteristics of all PLCs(as per 2015 WHO classification) were described prospectively over a period of two years (2014-2016).The antibodies that were used were TTF-1, napsin A, P40, CK7, CK20, vimentin, synaptophysin, chromogranin, BCL-2, CD34, LCA, CD99, AFP & bHCG. Results: We have studied 140 PLCs (78.6% male and 21.4% females) with age ranging from 25 to 85 years. Most common symptoms were cough and chest pain observed in 65% of our cases. In 14.2% cases the patients primarily presented with metastasis. The most common site was brain (40%), cervical nodes (45%) and skin (15%) in our record. There were 84cases of NSCLC and 5 cases of small cell carcinoma. 95.2% of NSCC could be further classified with the help of TTF-1,napsin A, CK7 & P40 into adenocarcinoma (71.4%), 23.8% cases of squamous cell carcinoma, and 4.8% of cases could not be subtyped further. TTF-1 was seen in all the cases of adenocarcinoma, whereas p40 was seen in all the cases of squamous cell carcinoma. Only in 4.8% of cases neither the morphology nor the staining pattern
S1125
supported adenocarcinoma or squamous and hence was diagnosed as NSCC-NOS. In addition to these usual types, other unusual morphological variants seen were3 cases each of carcinoid, large cell neuroendocrine carcinoma, & synovial sarcoma. There were also few rarer ones such as lymphoepithelioma like carcinoma, choriocarcinoma and yolk sac tumor. In 39 cases the biopsy was inadequate and hence could not be opined. Conclusion: Accurate categorization of primary lung tumors, has both therapeutic and prognostic significance. TTF1 and P40 are very sensitive markers for differentiating adenocarcinoma and squamous cell carcinoma of the lung. Addition of napsin A contributes to a higher sensitivity for adenocarcinomas. Keywords: Adenocarcinoma, TTF-1, Napsin A, SYNOVIAL SARCOMA
P3.01-012 P40 in Metastatic Pulmonary Trophoblastic Tumor: Potential Diagnostic Pitfall with Pulmonary Squamous Cell Carcinoma Topic: Morphology Deepali Jain,1 Archana Vallonthaiel,2 Raja Pramanik2 Pathology, All India Institute of Medical Sciences, New Delhi/India, 2AIIMS, New Delhi/India 1
Background: p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. Methods: We describe a case in which lung tumor was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. Results: A 36-year-old lady presented with cough and left sided chest pain for 2 months duration. Chest imaging revealed a lesion in left lower lobe of lung and biopsy was suggestive of squamous cell carcinoma (Fig 1). However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She developed similar nodules and ulcers over the left arm, followed by a gradually worsening dry cough and progressive shortness of breath. On imaging, she was found to have a septated left-sided pleural effusion. A positron emission tomographyecomputed tomography (PET-CT) revealed a large hypermetabolic soft tissue mass in left lower lobe with bilateral lung metastases and multiple liver deposits. On reviewing obstetric history, she also had a history of hysterectomy five years ago, details of
sectioning was recently described and termed Spreading Through A Knife Surface (STAKS). The purpose of this study was to prospectively examine lung resection specimens for the presence and frequency of STAKS. Methods: A prospective, multi-institutional study of NSCLC lobectomy and pneumonectomy resection specimen was performed from January 1 eJuly 1, 2016. Prosection, sampling and scoring of displaced fragments was undertaken in a systematic manner. The first cut was made with a clean long knife, the second cut was made in a parallel plane to the first cut, without cleaning the knife. Four tissue blocks were sampled: Block 1: first cut, upper part; Block 2: first cut, lower part; Block 3: second cut, upper part; Block 4: second cut, lower part. From these formalin fixed and paraffin embedded tissue blocks a superficial complete H&E stained slide was examined for the presence of displaced tissue fragments at 10 or 20. A displaced fragment was scored as STAKS if the tissue fragment was at least 0.5 mm from the tumor or if it was on the pleural surface in the plane of the second cut. Benign and malignant STAKS were separately noted. Results: A total of 41 resection specimen were included in this study. The mean number of malignant STAKS for blocks 1-4 was 0.36, 1.44, 1.86 and 1.95, respectively and for benign STAKS the mean number was 0.11, 0.11, 0.13 and 0.25, respectively. Almost all STAKS were intraalveolar. Comparison of malignant STAKS in block 1 (before the tumor was reached) with blocks 2-4 (containing tumor) was significant with p-values (p¼0.003 Friedman’s test and post-hoc comparisons p¼0.031, p¼0.002 and p¼0.005, respectively). For benign STAKS no difference was identified (p¼0.23). The chance of malignant STAKS seemed to be higher when tumor was cut fresh than when cut after formalin fixation.
Journal of Thoracic Oncology
Vol. 12 No. 1S
Ana Lopez Gonzalez,3 David Petite Felipe,4 Mariano Provencio Pulla1 1Oncology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/ Spain, 2Pathology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/Spain, 3Oncology, Hospital Universitario de Leon, Leon. Castilla Y Leon./Spain, 4 Radiology, Hospital Universitario Puerta de Hierro, Majadahonda Madrid/Spain Background: Giant cell carcinoma (GCC) of the lung is a subtype of sarcomatoid carcinoma (2015 WHO classification) traditionally associated with a highly aggressive clinical behavior. The histology consists in giant cells without differentiated carcinomatous elements. The aim of this study is to analyze the clinical, pathological and molecular features of seven GCC cases diagnosed in our hospital.
Topic: Morphology
Methods: Twenty-nine sarcomatoid carcinoma diagnosed in our hospital during the years 2009-2016 were reviewed and 7 cases with GCC histology were selected for the study. Immunohistochemical staining with antibodies targeting TTF1, napsinA, p40, and b-HCG were performed. ALK and MET status were assessed by FISH. EGFR mutations were performed using real-time PCR. Results: The patients were 4 men and 3 women with a mean age of 61 years (range 45-79). At the moment of diagnosis three patients were current smokers and 4 former smokers. Five cases were peripheral tumors, six in the left lung, and one in the right lung. Complete resection was achieved in all patients. Tumor staging showed 3 cases pT1; 3 with pT2 stage and one case pT3. Histopathologically, all were pure GCC and immunohistochemical stains revealed that the giant cells were negative for b-HCG in all cases except one who could not be analyzed. Two cases showed null phenotype (TTF1 and p40-negative), two cases were TTF1-negative and p40-positive, two cases co-expressed TTF1 and p40 and one case was TTF1-positive and p40-negative. NapsinA was positive in two cases. Molecular analysis was done in 6 cases and no EGFR mutation was detected. FISH results for c-MET probe showed a MET/CEN7 ratio <2 in all cases, polysomy with 5 MET signals without amplification was found in 5 cases. No ALK rearrangement was observed in the series. Five cases showed ALK copy number gain (3 to 5 fusion signals) and one case had two fusion signals. With a median follow-up of 38 months (5-130 months), two patients died due to brain metastases (both with vascular-lymphatic invasion and nodal metastases at the time of surgery), and five patients are alive at the moment of analysis.
Lourdes Gutierrez Sanz,1 Paloma Martin Acosta,2 Clara Salas Anton,2 Ana Isabel Fernandez Diaz,2 Diego Garcia Fresnadillo,2 Fernando Fabio Franco,1
Conclusion: Pure GCC is a very rare lung cancer subtype and there are few series reported. Lymphovascular invasion and lymph node involvement at diagnosis can predict a worse outcome in this subtype. GCC in our
Conclusion: The morphologic definition of STAKS is not different from STAS. This prospective study confirms the presence of benign and malignant STAKS. The presence of malignant STAKS is an artifact and increases with each and every knife cut during tissue sectioning. 1) Thunnissen et al. ArchPatholLabMed2016,140(212-220). Keywords: lung cancer, Pathology, ex-vivo artifacts, false positive diagnosis
P3.01-010 Primary Giant Cell Carcinomas of the Lung: Study of Seven Cases
January 2017
Abstracts
series do not have a specific immunohistochemical profile. Neither EGFR nor ALK were potential molecular targets, nevertheless c-MET status could be an interesting biomarker in GCC tumors. Keywords: Pathology, Giant cell carcinoma, cMET
P3.01-011 Clinocopathological Profile and Role of Immunohistochemistry in the Diagnosis of Primary Lung Cancer - A Prospective Study from Eastern India Topic: Morphology 1
2
Pritinanda Mishra, Susama Patra, Prasanta Mohapatra,3 Mamita Nayak,2 Radhamohan Gharei,2 Manoj Panigrahi,2 Sourin Bhuniya2 1Pathology, All India Institute of Medical Sciences, Bhubaneswar/India, 2All India Institute of Medical Sciences, Bhubaneswar/India, 3Pulmonary Medicine, All India Institute of Medical Sciences, Bhubaneswar/India Background: The clinico-pathological profile of lung cancer has changed considerably over the time in India. The histologic type also has changed from a predominant squamous histology to adenocarcinoma. We performed a prospective evaluation of primary lung cancers (PLCs) on the basis of clinical characteristics, histopathology and immunohistochemistry (IHC). Methods: The clinicohistopathological features and IHC characteristics of all PLCs(as per 2015 WHO classification) were described prospectively over a period of two years (2014-2016).The antibodies that were used were TTF-1, napsin A, P40, CK7, CK20, vimentin, synaptophysin, chromogranin, BCL-2, CD34, LCA, CD99, AFP & bHCG. Results: We have studied 140 PLCs (78.6% male and 21.4% females) with age ranging from 25 to 85 years. Most common symptoms were cough and chest pain observed in 65% of our cases. In 14.2% cases the patients primarily presented with metastasis. The most common site was brain (40%), cervical nodes (45%) and skin (15%) in our record. There were 84cases of NSCLC and 5 cases of small cell carcinoma. 95.2% of NSCC could be further classified with the help of TTF-1,napsin A, CK7 & P40 into adenocarcinoma (71.4%), 23.8% cases of squamous cell carcinoma, and 4.8% of cases could not be subtyped further. TTF-1 was seen in all the cases of adenocarcinoma, whereas p40 was seen in all the cases of squamous cell carcinoma. Only in 4.8% of cases neither the morphology nor the staining pattern
S1125
supported adenocarcinoma or squamous and hence was diagnosed as NSCC-NOS. In addition to these usual types, other unusual morphological variants seen were3 cases each of carcinoid, large cell neuroendocrine carcinoma, & synovial sarcoma. There were also few rarer ones such as lymphoepithelioma like carcinoma, choriocarcinoma and yolk sac tumor. In 39 cases the biopsy was inadequate and hence could not be opined. Conclusion: Accurate categorization of primary lung tumors, has both therapeutic and prognostic significance. TTF1 and P40 are very sensitive markers for differentiating adenocarcinoma and squamous cell carcinoma of the lung. Addition of napsin A contributes to a higher sensitivity for adenocarcinomas. Keywords: Adenocarcinoma, TTF-1, Napsin A, SYNOVIAL SARCOMA
P3.01-012 P40 in Metastatic Pulmonary Trophoblastic Tumor: Potential Diagnostic Pitfall with Pulmonary Squamous Cell Carcinoma Topic: Morphology Deepali Jain,1 Archana Vallonthaiel,2 Raja Pramanik2 Pathology, All India Institute of Medical Sciences, New Delhi/India, 2AIIMS, New Delhi/India 1
Background: p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. Methods: We describe a case in which lung tumor was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. Results: A 36-year-old lady presented with cough and left sided chest pain for 2 months duration. Chest imaging revealed a lesion in left lower lobe of lung and biopsy was suggestive of squamous cell carcinoma (Fig 1). However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She developed similar nodules and ulcers over the left arm, followed by a gradually worsening dry cough and progressive shortness of breath. On imaging, she was found to have a septated left-sided pleural effusion. A positron emission tomographyecomputed tomography (PET-CT) revealed a large hypermetabolic soft tissue mass in left lower lobe with bilateral lung metastases and multiple liver deposits. On reviewing obstetric history, she also had a history of hysterectomy five years ago, details of