Primary Lung Origin Research Articles

Primary pulmonary Ewing sarcoma: a rare case report

Ewing sarcoma (ES) is a malignant soft tissue tumor that consists of undifferentiated neuroectodermal cells. The anatomical sites of ES are commonly the pelvis and long bones. Metastasis is the cause of the most prevalent pulmonary ES. The primary lung origin of ES is extremely uncommon. Here, we report a rare case of primary pulmonary ES diagnosed from cytology and biopsy material. A chest X-ray revealed a lesion with a 9 × 7.5 cm diameter in the pericardiac area of the right lung. Clinical and radiological examinations (computed tomography and positron emission tomography) demonstrated that the lesion was a primary lesion. No distant metastasis was detected. Bronchoscopy-guided fine-needle aspiration and cytological analysis of the lesion revealed uniformly shaped small round cell morphology. Immunohistochemistry performed on the cell block produced positive results for CD99 and FLI-1. These immunohistochemical findings support the ES diagnosis.

SAT531 Thyroid Metastasis From Non-small Cell Lung Cancer: An Unusual Case Presentation

Abstract Disclosure: E.Y. Ibrahim: None. I. Guillen Alvarez: None. I. Hulinsky: None. D. Regelmann: None. C. Janowiecki: None. Background: Cases of thyroid tumors metastasizing from the lungs are rare, and their diagnosis is often challenging and can be mistaken for primary thyroid tumors or subacute thyroiditis. Thyroid function tests are typically normal and not helpful in establishing the diagnosis. Ultrasonography commonly shows focal or diffuse hypoechoic lesions. Correspondingly, heterogeneous hypodense areas with mild contrast enhancement are seen on CT scans. Clinical Case: Our patient is a 61-year-old male with a history of diabetes mellitus and 40 years tobacco use, who presented with a 1-week history of right-sided weakness and 3-weeks of dry cough. The weakness of his leg progressed to the point he could not ambulate. Initially, he was evaluated for a stroke and underwent CT imaging showing extensive lesions of the bilateral frontal, temporal, and parietal lobes. These findings were suspicious, and confirmed by MRI, to reflect multifocal metastatic lesions with vasogenic edema. Initial physical examination revealed a palpable thyroid nodule in the right lobe with bilateral cervical lymphadenopathy. CT of the neck demonstrated lymphadenopathy as well as multiple bilateral hypoechoic thyroid nodules, the largest of which measured 0.8 cm in the right thyroid lobe. TSH was 0.34 (0.48-4.17mU/L) with Free T4 at 1.39 (0.8-1.90ng/dL). The patient had denied symptoms of heat intolerance, tremor, or palpitations. A CT chest with contrast found a 3.5 cm cavitary lesion in the right upper lobe concerning for a primary lung neoplasm, as well as multiple bilateral lung nodules, mediastinal and hilar lymphadenopathy, and bilateral adrenal masses. Subsequent ultrasound-guided biopsy of the thyroid tumor revealed histologic features of a poorly differentiated non-small cell carcinoma, with features of a primary lung origin. These features were also present on a concurrent fine needle biopsy of an enlarged cervical lymph node. Immunohistochemistry staining showed the tumor was highly expressive for PDL1, focally positive for p40, pancytokeratin AE1/AE3, and negative for TTF-1 and thyroglobulinDue to the vasogenic cerebral edema, he was given dexamethasone with good response, and his weakness improved to the point that patient was able to ambulate. Treatment also included radiation therapy with subsequent pembrolizumab upon completion of radiotherapy. Conclusion: Several thyroid lesions representing metastases may go unnoticed because the physician’s attention toward lesions at other, more common sites, and detailed thyroid examination can be commonly overlooked. Patients with newly diagnosed malignancies should also be screened for thyroid involvement, including detailed physical, radiographic, and histologic examination of pathologic findings. Presentation Date: Saturday, June 17, 2023

Primary Endobronchial Conventional Chondrosarcoma Right Lung Upper Lobe: A Case Report and Literature Review

Primary endobronchial chondrosarcoma is extremely rare and hardly reported while reported chondrosarcomas of primary lung origin are rare with most literature coming from a series of case reports and small case series. These tumours can present as centrally located masses and therefore, require extensive workup to exclude alternative aetiology and to confirm diagnosis. Literature review revealed only four reports of primary endobronchial and 29 primary pulmonary chondrosarcoma cases, excluding the current report. We present a rare case of biopsy-proven non-metastatic primary endobronchial conventional chondrosarcoma of the right upper lobar bronchus extending into the right main bronchus managed with technically challenging sleeve bilobectomy of right upper and middle lobes and a viable anastomosis of lower lobe bronchus with the right main bronchus stump and thus, prevented a pneumonectomy. Final histopathology confirmed the diagnosis. Thus, these tumours are difficult to diagnose and challenging to manage and need more data in future to establish protocols.

Abstract 5: Alveolar epithelial type 1 cells can serve as a cell of origin for lung adenocarcinoma with distinct molecular and phenotypic presentation

Abstract Lung adenocarcinoma (LUAD) is the most common subtype of cancer arising in the distal lung. LUAD encompasses several pathologic histologies, some with important differing clinical outcomes and biological behaviors. However, the molecular and cellular underpinnings of the different subtypes are largely unknown. Understanding which cell populations in the distal lung contribute to LUAD could provide insights into the marked heterogeneity in pathologic features, clinical presentation and responses to therapy of LUAD. Differential expression analysis of LUAD transcriptomes from The Cancer Genome Atlas revealed distinct alveolar epithelial type 1 (AT1) and alveolar epithelial type 2 (AT2) cell signatures with significantly different survival outcomes between tumors expressing AT2 and AT1 gene signatures. The data suggests that AT1 cells might contribute to a subset of LUAD cases. To determine if AT1 cells could give rise to LUAD, we utilized transgenic mouse models to induce KrasG12D, a known oncogenic driver of human LUAD, in Gram-domain containing 2 (Gramd2)+ expressing AT1 cells. This gave rise to multiple LUAD lesions, as confirmed by micro computed tomography and pathologist-evaluated hematoxylin and eosin staining, primarily of papillary histology. In contrast, activation of KrasG12D in surfactant protein C (Sftpc+) AT2 cells resulted in LUAD lesions of exclusively lepidic histology. Immunohistochemistry established that Gramd2:KrasG12D lesions were of primary lung origin and not metastatic events. Spatial transcriptomic profiling revealed distinct pathway alterations within Gramd2- and Sftpc-derived LUAD, including specific upregulation of TGFβ-mediated epithelial to mesenchymal transition (EMT) in Gramd2+ AT1 LUAD. Immunofluorescence confirmed differences observed in the spatial transcriptomic analysis in expression patterns and distribution of cell-specific markers depending on cell of origin, while universal upregulation of a Krt8+ intermediate cell state marker was observed. Our results are consistent with Gramd2+ AT1 cells serving as a putative cell of origin for LUAD and suggest that LUAD may be a collection of adenocarcinomas that share a common location within the distal lung but arise from different cells of origin, a finding with potentially important therapeutic implications. Citation Format: Minxiao Yang, Hua Shen, Per Flodby, Michael Koss, Rania Bassiouni, Yixin Liu, Theresa Ryan Stueve, Daniel J. Mullen, Amy L. Ryan, Tea Jashashvili, John Carpten, Alessandra Castaldi, W. Dean Wallace, Beiyun Zhou, Zea Borok, Crystal N. Marconett. Alveolar epithelial type 1 cells can serve as a cell of origin for lung adenocarcinoma with distinct molecular and phenotypic presentation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5.

A CASE OF SCLEROTIC BONE METASTASIS AS A PRESENTATION OF LUNG ADENOCARCINOMA

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Lung Cancers are the third most common cause of bone metastasis. It occurs in 30-40% of patients during the course of illness. Osteolytic lesions are the most common histopathologic form of bone metastasis of lung origin. Although sclerotic bone changes have been reported in patients with NSCLC undergoing treatment with TKI (Tyrosine Kinase Inhibitors), Lung adenocarcinoma rarely presents initially with sclerotic bone metastasis. Here we have a patient with no prior history of lung cancer or chemotherapy who presented sclerotic bone metastasis originating from a Lung adenocarcinoma. CASE PRESENTATION: A 69-year-old male with no history of smoking presented to the ED with a one-month history of severe progressive lower back pain that radiates to bilateral upper thighs. He also had left shoulder pain that affected his daily activities and sleep. His condition was associated with 15 Ib weight loss over the last 3 months prior to presentation. The patient did not report any respiratory symptoms but he reported chronic difficulty urination, hesitancy, and frequency. A CT lumbar spine was remarkable for diffuse sclerosis of the L4 vertebral body. MRI confirmed that the L4 vertebral body has been replaced by a sclerotic metastatic lesion, as well as a 2nd metastasis present in the left side of L1. Given the dense sclerosis, Prostate Cancer metastasis was highly suggested. A rectal exam revealed no suspicion for malignancy and PSA was normal at a value of 1.020 ng/ml. Bone scan showed intense activity of L4, left side of L1, the proximal left humerus, and right scapula. A CT chest showed a 2.5 cm x 1.5 cm x 1.8 cm mass in the superior segment of the LLL. CT-guided bone biopsy was performed, which showed a metastatic adenocarcinoma of primary lung origin. Lab workup showed normal CBC, Calcium level, kidney and liver functions. The patient was stable so he was referred to Hematology/Oncology clinic for further management. DISCUSSION: Bone is the preferred site for metastasis for some of the most common malignancies, including Prostate, Breast, and Lung cancers. Bone metastasis is classified as osteolytic, osteoblastic, or mixed, according to the primary mechanism of interference with normal bone remodeling and the radiographic appearance. Osteolytic bone lesions are the typical picture for bone metastasis originating from non-small cell lung cancer. Also, It had been noticed that patients with osteolytic metastasis with EGFR mutation would have an osteoblastic reaction during treatment EGFR-TKI which may indicate a good treatment response. Only very few cases have been reported in the literature that presented initially with osteoblastic bone metastasis originating from non-small cell lung cancer, as what we have here in this patient. The exact mechanism of osteoblastic bone metastasis in NSCLC is not fully clear yet. CONCLUSIONS: Lung adenocarcinoma may present with sclerotic bone metastasis REFERENCE #1: Mutational profiling of bone metastases from lung adenocarcinoma: results of a prospective study (POUMOS-TEC) 2014 Oct 1Cyrille B Confavreux, a,1,2 Nicolas Girard,3 Jean-Baptiste Pialat,1,4 Pierre-Paul Bringuier,5,6 Mojgan Devouassoux-Shisheboran,6,7 Jean-Charles Rousseau,1 Sylvie Isaac,8 Françoise Thivolet-Bejui,9 Philippe Clezardin,1 and Marie Brevet1, REFERENCE #2: Osteoblastic Bone Lesions Developing During Treatment with Erlotinib Indicate Major Response in Patients with Non-small Cell Lung Cancer: A Brief Report April 1010 Joline S.W.LindMBBS, MAPieter E.PostmusMD, PhDEgbert F.SmitMD, PhD REFERENCE #3: David Roodman G, Silbermann R. Mechanisms of osteolytic and osteoblastic skeletal lesions. Bonekey Rep. 2015;4:753. Published 2015 Oct 28. doi:10.1038/bonekey.2015.122 DISCLOSURES: No relevant relationships by Ibimina Dagogo-Jack, source=Web Response No relevant relationships by Maged Ghaly, source=Web Response No relevant relationships by Sukhmanjot Kaur, source=Web Response

1812P Clinical and pathological features and prognosis of non-small cell lung cancer (NSCLC) patients with adenocarcinomas without TTF1 and Napsin A expression

At the present time, TTF-1 seems to be the single best marker for adenocarcinoma. TTF-1 helps to confirm a primary lung origin in 75 to 85% of lung adenocarcinoma. But in the remaining lung adenocarcinoma patients (pts) TTF-1 is not expressed. Detailed clinical, pathological and molecular features about last mentioned subgroup of pts is lacking. Furthermore, enteric differentiation can occur in lung adenocarcinoma, and when this component exceeds 50%, the tumor is classified as pulmonary adenocarcinoma with enteric differentiation (PAED) and detailed characteristics of these pts are lacking too.

48-Year-Old Woman With Dyspnea and Chest Pain

48-Year-Old Woman With Dyspnea and Chest Pain

Clinicopathological Spectrum of Primary and Metastatic Neuroendocrine Neoplasms.

IntroductionNeuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with histological features varying from well-differentiated neuroendocrine tumors (WDNETs) to poorly differentiated neuroendocrine carcinomas (PDNECs). In this study, we investigated the clinicomorphological spectrum of NENs including tumor grade, site of origin, and metastasis.MethodsWe retrospectively studied 125 cases of NENs (at the Department of Histopathology, Liaquat National Hospital and Medical College, Karachi) between the years 2014 and 2020. Slides of these cases were retrieved from the departmental archives and were evaluated for the tumor type, grade, and site of origin.ResultsThe mean age of the patients was 51.25±16.10 years. Overall, the liver was the most common site of the tumor (27.2%), followed by the small bowel (15.2%). Grade 2 was the most common tumor grade (40.8%), and most of the tumors were primary (68.8%). A total of 84.8% of the tumors were WDNETs/carcinoids, while 15.2% were PDNEC. The small bowel was the most common site of primary NENs, followed by the stomach and lung. Among primary neuroendocrine tumors, patients with PDNEC were significantly noted to have a higher mean age than WDNET/carcinoid. Similarly, PDNEC had a higher ki67 index than WDNET/carcinoid. For metastatic NENs, the liver was the most common site of metastasis (71.8%) with the GI/pancreatobiliary tract being the most common primary site of origin (51.3%). Tumors with primary lung origin were found to have a higher tumor grade than primary GI/pancreatobiliary tract origin NENs (p<0.0001).ConclusionIn this study, we found that the small intestine and liver were the most common sites for primary and metastatic NENs, respectively. Moreover, primary PDNECs were associated with a higher mean age than WDNETs. Alternatively, metastatic NENs with primary lung origin had a higher tumor grade than primary GI/pancreatobiliary tract origin.

Lung Adenocarcinoma with Gingival Metastasis.

Gingival metastasis of lung cancer is uncommon. We report the case of an 82-year-old male smoker admitted to the pulmonology department with right pleural effusion. A chest computed tomography (CT) scan showed an invasive right hilar tumour, adherent to the superior vena cava, pulmonary artery, main right bronchus, mediastinal pleura and pericardium with lymphangitic carcinomatosis of the right lung. Pleural biopsy revealed pleural metastasis of pulmonary adenocarcinoma, its primary lung origin being confirmed by immunohistochemistry. One month later, the patient developed an ulcerated polypoid gingival mass. Biopsy of this lesion showed a poorly differentiated carcinoma compatible with metastasis from the lung adenocarcinoma. The patient underwent irradiation of the gingival mass at a dose of 30 Gray, but his condition worsened rapidly and he was not fit for chemotherapy. He received palliative treatment and died 2 months after diagnosis of his metastatic lung cancer.LEARNING POINTSLung cancers mostly metastasize to the bones, liver, lymph nodes, brain, lung and adrenal glands, with adenocarcinoma being the most common histological type.Distant metastasis to the oral region is very uncommon but can be the first manifestation of a primary tumour.Oral metastasis can be mistaken for a benign lesion, so a biopsy should be taken for further analysis.

Frequency of ALK Rearrangement by FISH Testing and its Correlation with ALK-IHC in Adenocarcinoma of Primary Lung Origin

Anaplastic lymphoma kinase (ALK) gene can be oncogenic either by forming fusion with other genes, amplification of the gene or by having mutations. ALK rearrangement can either be detected by standard “fluorescence in situ hybridization (FISH)” or “immunohistochemistry (IHC)”. Objective of this study was to record the prevalence of ALK rearrangement in adenocarcinoma of Primary Lung origin and compare it with ALK-IHC staining. Data of 64 patients of lung adenocarcinoma from 2015-2017 was analyzed. All of the FFPE biopsies were tested for EGFR (qPCR) followed by ALK rearrangement (by FISH and IHC) on EGFR negative samples. Out of 64 samples, 21.8% (14) showed EGFR mutations and 14% (7/50) were positive for ALK rearrangement when checked by FISH. In IHC testing for ALK (FISH positive) 8% (4/50) showed positivity. In conclusion ALK-FISH positive cases are higher than other studies likely due to the relatively small sample size. FISH testing was found to be more sensitive than IHC; one reason may be the low level of ALK. Our study warrants that currently FISH remains the gold standard for screening of ALK gene rearrangements.

Duodenal Metastases from Primary Large Cell Carcinoma of the Lung Presenting with Melena

Introduction: Duodenal metastases from primary lung cancer is very rare and does not usually cause symptoms. We report a case of duodenal metastatic lesions of primary lung origin presenting with melena. Case Report: A 76 year-old male smoker with atrial fibrillation on anticoagulation and chronic obstructive pulmonary disease presented to the emergency department with cough, weight loss and melanotic stools for 1 week. Laboratory studies revealed a hemoglobin (Hb) of 7.7g/dL. Upper and lower endoscopy did not reveal an obvious source of bleeding and the patient was discharged in stable condition. On investigation for progressive cough and shortness of breath, a CT scan was performed and identified a 3cm right hilar mass, precarinal and subcarinal lymphadenopathy, and a 2.4cm soft tissue mass adjacent to the distal duodenum. Bronchoscopy did not show evidence of malignancy and the patient was scheduled for an endobronchial ultrasound (EBUS) with mediastinoscopy. However, due to recurrent episodes of melena with a Hb of 6.6g/dL, EBUS was postponed. Repeat CT scan showed mesenteric lymphadenopathy and thickening of the distal duodenum. An upper endoscopy with push enteroscopy was performed and identifed multiple, large ulcerations in the third and fourth portions of the duodenum without active bleeding. Biopsies were taken and pathology revealed large cell carcinoma consistent with metastases of pulmonary origin. Subsequent EBUS with fine needle aspiration of the lymph nodes confirmed the diagnosis.Figure 1Discussion: Duodenal metastases from primary lung cancer presenting with melena is exceedingly rare and usually indicates terminal stage with poor prognosis. Of the few studies reported to date, the prevalence of small bowel involvement ranges from 0.5% to 10.6%, including results from autopsies. Small bowel metastases have been reported to occur in the setting of gynecologic malignancies (ie. uterine) with jejunal and ileal involvement being the most common. Symptoms from duodenal metastases are infrequent and rarely present at or prior to the time of the cancer diagnosis. Depending on the size and location of the lesions, however, clinical features may include melena with a microcytic anemia, malabsorption, obstruction, and more commonly, perforation. Therefore, metastatic small bowel disease should be included in the differential diagnosis of gastrointestinal bleeding in a patient presenting with constitutional features suggestive of an underlying malignancy.

Distribution of EGFR mutations commonly observed in primary lung adenocarcinomas in Pakistan as predictors for targeted therapy.

Acquired genetic alterations and presence of sensitizing mutations in the tyrosine kinase domain of EGFR and other signaling molecules have been found in different subsets of primary lung adenocarcinoma. The commonest EGFR mutations are small in frame deletions of exon 19 and a point mutation (L858R) in exon 21, having a combined occurrence of around 90%. The objective of this study was to determine the frequency and types of EGFR mutations in primary lung adenocarcinomas in Pakistan. EGFR mutations in tumor samples were screened by multiplex real time PCR. Briefly, DNA from formalin fixed paraffin-embedded tissue was amplified with primers and probes specific to 43 different EGFR mutations in a Cobas z 480 instrument. The assay detects mutations in four exons (18-21) of the EGFR gene. Out of 94 patients, 65 were males and 29 females with a M:F ratio of 2.2: 1. The median age was 62 years (range, 28 - 85 years). In our biopsy samples 70 (74%) cases were of primary lung adenocarcinoma, whereas 24 (26%) were confirmed metastatic adenocarcinoma of primary lung origin. EGFR mutation was positive in 29% of the patients. The highest frequency of L858R was observed in 48% of these, followed by deletion in exon 19 (44%). In addition, other rare mutations such as compound G718X:S768I and insertions in exon 20 insertion were detected in approximately 4% of the patients. This study showed that Del 19 and L858R are the most frequent mutations in Pakistani lung adenocarcinoma patients and around 29% of the patients were found eligible for erlotinib therapy.

Carcinoid tumor of the lung metastatic to a previously identified pituitary adenoma.

The authors present the case of a 58-year-old gentleman presenting with atypical carcinoid tumor of primary lung origin metastasizing to a previously identified pituitary macroadenoma. The patient presented with symptoms of headache and visual disturbance. Imaging revealed enlargement of a known sellar mass as well as three separate enhancing lesions in the brain parenchyma. Resection was accomplished via a transnasal transshpenoidal approach without complication. Immunoreactivity was demonstrated to synaptophysin, chromogranin, CD56, epithelial membrane antigen, and thyroid transcription factor-1. The specimen was also marked by negative staining for pituitary hormones. This case demonstrates a rare occurrence of metastastic spread of tumor to a previously identified pituitary macroadenoma.

Oncogene Expression Detected by in situ Hybridization in Human Primary Lung Cancer

By means of in situ hybridization using biotinylated oncogene probes and the immunohistochemical reaction of avidin-biotin complex-alkaline phosphatase with substrate, we investigated expression of c-myc oncogene in the formalin-fixed, paraffin-embedded tissue sections from seven patients with squamous cell carcinoma (six cases) and small cell carcinoma (one case) of primary lung origin. The expression of c-myc oncogene was greatly enhanced in all cases studied, with individual and cell-to-cell variation. In contrast, all of the specimens incubated with deoxyribonuclease after the standard pretreatment with ribonuclease T1 were negative for the expression of c-myc oncogene. The in situ hybridization permits estimation of a heterogeneous amplification of c-myc oncogene that may be related to secondary alterations occurring during the progression of the malignant lung tumors.