Case Of Metastatic Lung Adenocarcinoma Research Articles

Surgical Treatment and Clinical Evaluation of Calvarial Metastases.

The aim of this study is to explore surgical treatment techniques and clinical attributes associated with calvarial metastases, while providing a comprehensive review of the treatment experiences relevant to this particular type of tumor. This study involves a retrospective analysis of clinical data from 12 patients diagnosed with calvarial metastatic tumors who underwent surgical intervention. Among these patients, 5 had a history of previous malignant tumor resections, while 7 presented with calvarial metastatic tumors as their initial symptom. In all cases, the surgical approach consisted of calvarial tumor resection followed by titanium mesh repair. Following the surgical intervention, all patients underwent a comprehensive course of treatment, encompassing both local radiotherapy and systemic chemotherapy. In 1 instance, a patient presented with multiple tumors located in the central area of the frontal bone and the right temporal bone. The larger tumor situated in the middle of the frontal bone was surgically excised, while the tumor in the right temporal bone was treated using radiotherapy. In 2 cases characterized by multiple metastases within the skull, a comprehensive excision of all tumors was accomplished in a single surgical procedure. In the remaining cases featuring a solitary metastatic growth, the respective tumors were surgically removed. There were 10 instances of dura mater invasion and 3 cases involving the invasion of brain tissue. Pathologic examinations revealed 1 case of metastatic lung adenocarcinoma, 1 case of metastatic paraganglioma, 1 case of metastatic hepatocellular carcinoma, 2 cases of metastatic thyroid carcinoma, and 7 cases of metastatic clear cell renal cell carcinoma. Throughout the follow-up period, spanning from 14 to 90 months, various outcomes were noted. These included three occurrences of in situ recurrence. In addition, 1 patient required 3 distinct surgical interventions, while 2 other patients underwent 2 separate surgical procedures each. Notably, 1 of these cases involved the exposure of the titanium mesh on the scalp, necessitating the removal of the titanium mesh. Regrettably, there have been 9 recorded fatalities among the patients, while 3 individuals have survived. Solitary metastasis of calvarium region is rare, and surgical resection is effective. However, it is necessary to extend the resection range and combine with local radiotherapy to avoid local recurrence. Surgical intervention can significantly enhance the quality of life for affected patients. The prognosis of the patients mainly depends on the treatment of the primary disease and the situation of important organ dissemination and treatment.

Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity

Objective: To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion. Methods: Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma). Results: Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion. Conclusion: By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

Lung Adenocarcinoma Metastatic to the Cervix: Report of a Rare Case and Review of the Literature

Abstract Metastatic involvement of the cervix by nongynecologic malignancies is an extremely rare occurrence. We report a case of metastatic lung adenocarcinoma to the cervix. The patient is a 70-year-old woman who was admitted because of acute kidney injury. Imaging studies revealed left-sided hydronephrosis and a 3.2-cm heterogeneous pelvic mass involving the left pelvic wall. The patient underwent hysteroscopy with dilatation and curettage. Specimens labeled with endometrial and endocervical curettings were notable for tumor cells infiltrating the fibromuscular tissue. Immunohistochemical studies showed that the tumor cells were positive for CK7, napsin A, and TTF1, whereas they were negative for PAX8, p16, p40, p53, GATA3, and ER. This immunophenotype was consistent with a metastatic adenocarcinoma of the lung primary.

Accuracy of Subclassification and Grading of Renal Tumors on Fine Needle Aspiration Cytology Alone

Background: Fine needle aspiration (FNA) of renal masses can distinguish between benign and malignant neoplasms in 73–94% of cases. Previous studies suggested the correct subclassification of renal cell carcinomas (RCCs) by cytomorphology can be achieved in up to 80% of cases. However, as RCCs become increasingly subclassified by molecular signatures, correct subclassification based on cytology alone is increasingly difficult. Design: Two FNA passes (2 stained with Diff-Quik® and 2 with the Papanicolaou method) were performed on all fresh nephrectomy specimens for a 1-year period. There were 30 cases in this study, with 29 primary renal tumors and 1 case of metastatic lung adenocarcinoma. Each case was assigned a random number and came with 2 slides (1 from each staining method). Eight cytopathologists were asked to provide a diagnosis and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading if applicable. Fleiss’ Kappa and Cohen’s Kappa equations were used to look at inter-rater variability. Results: When compared to the surgical pathology diagnosis, the average percent correct diagnosis for all cytopathologist was 35%. Chromophobe RCCs had the best average percent accuracy at 72% followed by clearcell RCC at 48%. Average accuracy for grading RCCs was 40%. Inter-rater variability among the cytopathologists for all RCC diagnoses was fair with a Fleiss’ Kappa coefficient of 0.28. For the WHO/ISUP grade, the weighted coefficient for each pathologist ranged from 0.11 to 0.45, ranging from fair to moderate, respectively. Conclusions: Renal tumors are difficult to classify on cytopathology alone. Core needle biopsy and ancillary studies are necessary if diagnosis will change management.

Isolated abducens nerve palsy secondary to lung metastases

We present a rare case of metastatic lung adenocarcinoma which presented as isolated abducens nerve palsy. A 65-year-old healthy woman presented with horizontal diplopia of three months duration. Her best-corrected visual acuity was 6/18 bilaterally with no relative afferent pupillary defect. Ocular examination showed limited abduction of the right eye. Anterior and posterior segment examination was normal in both eyes. However, she had a non-tender enlarged lymph node at the left supraclavicular area. The systemic review was unremarkable.C-reactive protein, erythrocyte sedimentation rate, and serum alpha-fetoprotein were markedly raised. A chest X-ray revealed right upper lobe opacity with a satellite nodule. Computed tomography of the brain, orbit, thorax, abdomen, and pelvis exhibited a heterogeneously enhancing mass at the right upper lobe of the lungwith metastasis to the left frontal, right occipital, and left parietal lobe as well as multiple bone metastases. With histopathology confirmation of lung tissue biopsy, she was diagnosed as isolated right abducens nerve palsy secondary to metastatic lung adenocarcinoma. She was referred to the respiratory, neuromedical, andoncology units for further management. In conclusion, although this appeared to be an isolated case, lung metastasis should be considered in the differential diagnosis of isolated abducens nerve palsy. Hence, lung examination should be performed when encountering such cases.

EP1.14-32 Pattern of EGFR Mutations and Response to First Generation EGFR TKIs in Patients of Metastatic Lung Cancer at a Tertiary Care Centre in India

EGFR gene mutations, ALK and ROS1 gene rearrangements represent the most common targetable lesions in the era of TKIs for treatment of metastatic lung cancer. Use of TKIs improves overall survival compared to cytotoxic chemotherapy in these patients. The objective of the study was to identify the prevalence and pattern of EGFR mutations and their response to TKIs in Indian patients. Histopathologically confirmed cases of metastatic lung adenocarcinoma diagnosed between 2016 to 2018 at Kidwai Cancer Institute, Bangalore were reviewed for their EGFR mutation, ALK and ROS1 gene rearrangement status. DNA was extracted from formalin fixed paraffin embedded tissue and tested for EGFR hotspot mutations (Exon 19 deletions, exon 20 insertions and substitution mutations G719X, S768I, T790M, L858R and L861Q in exons 18, 20 and 21 of the EGFR gene) using ARMS real-time PCR. ALK and ROS1 rearrangement was tested using IHC with primary antibody ALK D5F3 and ROS1 D4D6 respectively. Tabled 1Complex EGFR mutationsPATIENT IDEGFR MUTATIONTREATMENTPFS ( MTHS)51EXON 19 DEL + T790MChemotherapy61626EXON 19 DEL + L858RGefitinib6164S768I + L858RGefitinib2208L858R + T790MChemotherapy3229EXON 19 DEL + T790MChemotherapy4 Open table in a new tab A total of 240 patients underwent testing. EGFR mutations were detected in 31.6% (n =76) and ALK and ROS1 rearrangement in 7% (n=17) and 1.25% (n=3) of the patients. The most common EGFR mutation was exon 19 deletions (e19 del) (n=44; 57.9%) followed by L858R mutation in exon 21 (n=23; 30.3%). Double EGFR mutations was seen in 5 patients (6.6%) and 3 patients had L861Q mutation. One patient had upfront T790M mutation. Median age was 54 years (range 35 -78 years). Male to female ratio was 0.9. 43.45% (n=33) were never smokers. Gefitinib was advised in 50 patients (65.8%), Erlotinib in 21 patients (27.6%) and rest were treated with chemotherapy. Median PFS in patients with e19 del, L858R and other mutations was 11, 12 and 4 months respectively. The prevalence of EGFR mutations in our studies are similar to those reported from other parts of India, lower than that from other Asian countries and higher than that from Western countries. E19 del and L858R mutations respond favourably to TKIs, but complex mutations do so poorly. Use of TKIs other than Gefitinib and Erlotinib need to be explored in these cases to improve outcomes.

METASTASIS AROUND DENTAL IMPLANTS MASCARAING AS PERI-IMPLANTITIS - A WOLF IN SHEEP'S CLOTHING

Background Placement of dental implants is a common procedure with a high success rate. A minority of the cases fail, however, a manifestation termed peri-implantitis, which is considered clinically obvious, hence often not biopsied. Case report In this report, a case of metastatic lung adenocarcinoma mimicking peri-implantitis adjacent two dental implants is presented. The lesion occurred eight months after the surgical implantation procedure and by that time, the underlying malignancy was unknown to the patient. During the surgical procedure itself’, and even in the follow up meetings, there was no apparent clinical or radiographic sign of a metastatic disease, but during an eight months follow up session, the soft tissue around the implants was firmly swelled and mildly erythematous, and the x ray imaging revealed a nonspecific ill-defined radiolucency of the alveolar bone. The tissue was excised, adjacent bone was curated and the tissue was submitted to histopathological analysis. The pathological picture presented a malignant tumor composed of epithelial islands embedded within a fibrous stroma. The epithelial islands presented atypical features and an immunohistochemical phenotype of lung adenocarcinoma that included positive pan keratin, thyroid transcription factor-1 and napsin-A and negative thyroglobulin and prostatic specific antigen. Concurrently, the patient was diagnosed with a lung adenocarcinoma and started systemic treatment. Conclusion This case of metastatic disease masquerading as peri-implantitis reflects the importance of submitting any tissue to histopathological assessment.

A Case of Lung Adenocarcinoma with Metastasis to the Breast

The breast is a rare site of metastasis from cancers that seldom occurs late in the natural history of a malignancy. It causes a diagnostic challenge when it is an early presentation of cancer. Here, we report a case with an incidental breast mass. Further evaluation of the histology revealed a contralateral lung adenocarcinoma. The metastatic deposit of the breast responded well to systemic therapy and therefore the patient was selected for aggressive local therapy of the primary site. The aim of the present study is to report a rare case of metastatic lung adenocarcinoma with limited metastasis that was diagnosed as a non-primary breast neoplasm and was treated with chemotherapy, surgery, and consolidative radiotherapy with a curative intent.

Lung Cancer Metastatic to Breast

The incidence of metastases to the breast from nonbreast carcinoma is less than 1% of all breast cancers; of these, adenocarcinoma of the lung to breast is a small proportion (<0.1% of breast carcinomas). The imaging findings of a case of metastatic lung adenocarcinoma to the breast are presented with a review of the literature. Imaging findings including elastography suggesting the breast mass is not a primary breast cancer are highlighted. The importance of notifying the pathologist that nonbreast metastatic disease is in the differential is discussed. The use of appropriate tumor markers is needed; otherwise, the lesion may be interpreted as a triple negative breast cancer.

Dramatic responses to gefitinib when used as front line therapy in two cases of metastatic lung adenocarcinoma with poor performance status

A 54-year-old man, a non-smoker, suffering from metastatic lung adenocarcinoma presented with extensive bilateral pulmonary infiltrates. He was dyspneic at rest. Performance status (PS) was 4. Institution of gefitinib resulted in relief from dyspnea within two weeks. Positron emission tomography done after 10 months revealed only a 2 cm residual lesion. However, the patient stopped therapy on his own and died two months later. An 80-year-old female, a non smoker, presented with metastatic lung adenocarcinoma and right sided pleural effusion. Her PS was 4. She was started on gefitinib. Within four weeks, she showed marked improvement. At six months, she was radiologically documented to be in partial remission. She continues to be asymptomatic at one year follow-up. These are the first reports of dramatic responses to gefitinib when used as front-line therapy in patients with poor performance status from India.

Large solitary cystic brain metastasis mimicking colloid cyst of the third ventricle

Metastatic lung adenocarcinoma to the brain is a common metastatic brain tumour [Won LLJ, Hyung KR, Moon CK, Chang RC. Metastatic mucinous adenocarcinoma mimicking cerebral haemorrhage. J Korean Neurosurg Soc 2003;34(3):252–3]. Brain metastases can occur at any location. However, metastases in the third ventricle are rare [Ozerk O, Ihsan S, Erkan K, Etem B. Intracranial metastasis of lung adenocarcinoma mimicking colloid cyst of the third ventricle. J Clin Neurosci 2006;13(4):487–9]. We report a case of metastatic lung adenocarcinoma to the brain mimicking a giant colloid cyst of the third ventricle.

Differentiation of mesothelioma from adenocarcinoma in serous effusions: The role of hyaluronic acid and CD44 localization

Differentiating cells of mesothelial origin from adenocarcinoma (ACA) based on morphology alone can be a diagnostic challenge, especially in cytological specimens. Malignant mesothelioma (MM) is characterized by accumulation of abundant intracellular hyaluronic acid (HA), a feature that is not reported in ACA. The purpose of this study was to evaluate the significance of cellular HA using an HA-specific binding peptide (HABP) and the expression of its principal receptor, the standard CD44 molecule (CD44S). Archival paraffin-embedded cell blocks of serous fluids from 28 cases of reactive mesothelial cells, 14 cases of MM, 20 cases of metastatic ovarian carcinomas, 17 cases of metastatic breast carcinomas, 12 cases of metastatic lung ACA, and 12 cases of metastatic gastrointestinal ACA were stained with HA using a biotinylated HABP and CD44S. Positive staining was defined as droplet to diffuse cytoplasmic staining for HA and uniform membranous staining for CD44S. All MMs and 93% (26/28) of the benign mesothelial cells were positive for intracytoplasmic HA vs. none of ACAs. CD44S was expressed in 100% (28/28) of mesothelial hyperplesia, 86% (12/14) of MMs, 70% (14/20) of ovarian carcinomas, 29% (5/17) of breast carcinomas, 25% (3/12) of gastrointestinal ACAs, and 8% (1/12) of lung ACAs. In MM and reactive mesothelial cells, CD44S stained cell membranes diffusely with highlights on the villous surfaces and in ACA it was focal and confined to cell membranes. Immunostaining with HA is a reliable marker that can distinguish between cells of mesothelial origin (reactive mesothelial cells and MM) and ACA. The CD44S staining pattern of cells of mesothelial origin is of diagnostic significance. CD44 may prove useful in conjunction with other stains in the differential diagnosis of mesothelioma and ADA.

Usefulness of TA02 (napsin A) to distinguish primary lung adenocarcinoma from metastatic lung adenocarcinoma

TA02 (napsin A) associated with primary lung adenocarcinoma detected by the two-dimensional polyacrylamide gel electrophoresis (2-DE), has a molecular weight of 35.0 kDa and an isoelectric point 5.29. We developed a mouse monoclonal antibody against the N-terminal of the TA02 molecule (clone TMU-Ad02 (6A1)) and attempted to investigate its immunohistochemical reactivity for nodular lesions of the peripheral lung, and evaluate its usefulness for making a differential diagnosis between primary and metastatic lung adenocarcinomas. The TA02-immunohistochemical evaluation was carried out using surgically resected materials of 109 cases of lung cancer (76 cases of primary lung cancer and 33 cases of metastatic lung adenocarcinoma from other organs), five cases with mesothelioma, four cases with atypical adenomatous hyperplasia (AAH) and five cases with tuberculoma of the lung. In 39 out of 43 (90.7%) primary lung adenocarcinomas, positive immunohistochemical reactivity with a granular cytoplasmic staining pattern was observed. Even though two out of seven (28.6%) large cell carcinomas showed positive results with a granular staining pattern, the immunohistochemical staining intensity was weak. The other cancerous lesions containing metastatic lung adenocarcinoma and mesothelioma were all completely negative. In comparison with the immunohistochemical reactivity of TA02 and SpA, TA02 was superior to SpA both in terms of positive rate and immunohistochemical intensity. We concluded that the evaluation of TA02 expression in lung tumorous lesions was very valuable for discriminating between primary and metastatic lung adenocarcinoma, and TA02 was superior to SpA as a discriminating marker.

Diagnostic Utility of Thyroid Transcription Factor–1 Expression in Adenocarcinomas Presenting in Serous Fluids

To evaluate the diagnostic utility of the immunohistochemical expression of thyroid transcription factor-1 (TTF-1) in adenocarcinomas from serous fluid specimens.Archival paraffin-embedded cell blocks of serous fluids from 82 cases, including 34 cases of metastatic lung adenocarcinoma, 12 of metastatic ovarian adenocarcinoma, 12 of metastatic breast adenocarcinoma, 12 of metastatic gastrointestinal adenocarcinoma and 12 of malignant mesothelioma, were immunostained with anti-TTF-1. All the staining was carried out using a Ventana Automated System. Staining was evaluated according to the intensity of the nuclear staining (1+ to 4+) by two observers.Of the metastatic lung adenocarcinomas, 79% (27/34) expressed 3+ to 4+ reactivity against TTF-1. None of the malignant mesotheliomas or other metastatic adenocarcinomas expressed nuclear reactivity.Immunostaining with TTF-1 is a useful marker that can be applied to cytologic specimens. Anti-TTF-1 can be used as a reliable component of an antibody panel to support the diagnosis of adenocarcinoma of pulmonary origin in patients presenting with metastatic adenocarcinoma in serous fluid with an unknown primary site.

Determination of lung as the primary site of cerebral metastatic adenocarcinomas using monoclonal antibody to thyroid transcription factor-1.

Determining the primary site of a cerebral metastatic adenocarcinoma is complicated by the histologic similarity of most adenocarcinomas. Thyroid Transcription Factor-1 (TTF-1) is a highly specific marker of peripheral airway cell neoplasms. Formalin fixed tissue from 30 patients with brain metastasis whose primary sources were clinically and histologically known with certainty were analyzed for immunoreactivity to TTF-1. There were 18 cases of metastatic lung adenocarcinoma. Other metastases were from breast (6), colon (1), prostate (1), kidney (1), paranasal sinus (1), melanoma (1), and intestinal carcinoid (1). No patients with carcinoma of the thyroid were found. Positivity was regarded as intense nuclear reactivity. Twelve (67%) metastatic lung adenocarcinomas stained for TTF-1. None of the cerebral metastases from other body sites showed positivity. In addition, normal brain tissue and astrocytic tumors did not stain for TTF-1. These data show that TTF-1 is a highly specific and reasonably sensitive marker for peripheral airway cell metastasis to the brain.