Additional Metastatic Lesions Research Articles

UTILITY OF CONTRAST-ENHANCED T2-FLAIR FOR IMAGING OF BRAIN METASTASESUSING A HALF-DOSE HIGH-RELAXIVITY CONTRAST AGENT IN COMPARISON WITH ROUTINE DOSE CONTRAST-ENHANCED BRAIN IMAGING

Aim & Objectives: This study aims to assess the efficacy of delayed contrast-enhanced T2 fluid-attenuated inversion recovery (CE-T2 FLAIR) by using half dose high relaxivity contrast agent to assess the degree of enhancement among the lesions and to detect additional metastatic brain lesions usually smaller lesions(<5mm), which are significantly missed on routine-dose CE-T1 weighted imaging (CE-T1WI). Material & Methods:The main source of data for this study was radiologically diagnosed lung cancer patients who were clinically suspected to have brain metastasis referred from various departments of Silchar Medical College and Hospital. The studywas carried out for a period of 1 year from March 1, 2023, to February 29, 2024, A total of 40 patients with brain metastases were scanned using a SIEMENS TIM AVANTO 1.5T scanner, routine MR pulse sequences pre- and post-contrast administration were acquired. Results: Out of 40 patients, males were more affected (57.5 %) than females (42.5 %). The highest number of cases were found between the 61-70 years age group with the lung (31 cases) being the most common primary malignancy causing brain metastases. A total of 90 lesions were detected among 40 patients which were grouped into A (25 lesions), B (36 lesions), and C (29 lesions) groups. A total of 6 lesions were missed on Routine dose contrast-enhanced brain imaging of which 2 lesions belong to group B (Rim enhancing lesions >5mm) and 4 lesions belong to group C (Lesions <5mm), however, these lesions were picked up on delayed half dose contrast-enhanced FLAIR images. The contrast ratio (CR) on 3 consecutive half dose CE-T2 FLAIR ranged between 59.09%-76.80%, suggesting that delay in imaging post-contrast administration resulted in a significant increase in the contrast ratio (CR) among metastatic lesions. Conclusions: CE-T1-weighted sequences and CE-T2 FLAIR sequences complement each other effectively in evaluating brain metastases. Bigger and homogenously enhancing lesions are best seen on CE-T1-weighted sequences. Smaller lesions and lesions showing rim enhancement are best visualized on delayed (5 min) CE-T2 fluid-attenuated inversion recovery (FLAIR) sequences with half the dose ofcontrast agent (gadobenatedimeglumine) compared to routine dose CE-T1-weighted sequences. This approach serves as a cost-saving measure for both patients and the healthcare system.

Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib-resistant MET exon 14 skipping mutated lung adenocarcinoma

Traditionally, the D1228 E/G/H/N mutation has been thought to cause Type I MET-TKI resistance. We reported a 75-year-old female with non-small cell lung cancer harboring MET exon 14 skipping mutation, who developed acquired MET D1228H mutation induced by capmatinib treatment. Interestingly, the patient demonstrated marked response to second-line savolitinib treatment with the duration of response of 19 months and several additional metastatic lesions appeared. Pathological assessment of rebiopsy sample showed adenocarcinoma and targeted next-generation sequencing revealed the loss of MET D1228H mutation and presence of MET p.Y1230N mutation. In response, the treatment regimen was amended to include a daily administration of 60 mg of cabozantinib, which resulted in moderate size reduction of the tumours. The switch of resistance mutations indicated that different type Ib MET inhibitors may exhibit distinct mechanisms of resistance. We call for futher studies on resistance based on patient-derived pre-clinical models including patient-derived tumor-like cell clusters, patient-derived organoids, and patient-derived xenografts.

Periprosthetic metastases in carcinoma of unknown primary: A rare association.

Septic or aseptic loosening may cause bone loss around artificial prosthesis leading to prosthesis failure. This occurrence due to metastatic infiltration of bone or surrounding soft tissues is rare but has been occasionally reported. We report a case of an elderly lady presenting with swelling and pain at the site of previous hemiarthroplasty performed for traumatic injury. On evaluation, she was found to have a lytic femur lesion with a large soft-tissue component around the prosthetic joint. Biopsy suggested a metastatic carcinoma of renal origin, but screening of kidneys did not reveal any primary lesion. She had additional skeletal metastatic lesions but no other primary site was detected either. She was given palliative radiotherapy and systemic therapy (sunitinib) based on the histologic diagnosis of renal cell origin but did not tolerate it. Thereafter, she is continuing on zoledronate every 4 weeks and best supportive management since 4 months from diagnosis.

Hepar-1 Positive Prostatic Adenocarcinoma: A Case Report and Review of Literature

Abstract Introduction/Objective Poorly differentiated metastatic malignancy in patients with a history of more than one known primary tumor, such as a history of both hepatocellular and prostatic carcinoma as seen in our case, can be challenging. Both tumors are CK7/CK20 positive, and both can be reactive for hepar-1, as has been demonstrated in the current case, and rarely described in the literature. Methods/Case Report Herein we present a sixty-three-year-old male who presented for follow-up of his lower back pain in the setting of hepatocellular carcinoma. MRI of the spine was suggestive of an expansile metastatic lesion in the C2 vertebral body with extraosseous soft tissue extension resulting in moderate to severe central canal and left foraminal narrowing at C2-3. Multiple additional metastatic lesions were visualized throughout the cervical upper thoracic spine as detailed above. Vertebral body biopsy showed metastatic adenocarcinoma with sheets of neoplastic cells infiltrating the medullary spaces. The patient’s history of hepatocellular carcinoma was noted, and immunohistochemical staining for HepPar1 with appropriate control was performed and found to be diffusely reactive in the tumor cells. However, tumor cells were also positive for PSA, PSAP, and NKX3.1 (Fig-1-A-D, H&E, Hepar-1, PSAP, PAP). This immunoprofile is consistent with a prostatic origin of the tumor cells, and a diagnosis of metastatic prostatic adenocarcinoma was given. Results (if a Case Study enter NA) NA. Conclusion Hepar-1 and even arginase-1 have been observed in rare subsets of prostatic acinar adenocarcinoma. Even in the setting of PSA and PSAP negative metastatic disease in patients with a history of hepatocellular carcinoma, we suggest utilizing additional stains suggestive of a prostatic origin, such as NKX3.1, and even molecular studies. This could be useful diagnostic approach to help differentiate between the two neoplasms in such patients.

Bladder Paraganglioma Presenting as Post-Micturition Syncope.

A 22-year-old woman presented with a 12-year history of intensifying paroxysms of anxiety, palpitations and recurrent syncope following micturition. The patient was referred to endocrinology upon discovery of hypertension. An extended family history revealed metastatic phaeochromocytoma and paraganglioma in two grand-uncles. Clinical examination revealed hypertension, with a mean 24-hour ambulatory blood pressure of 150/100 mmHg. Supine plasma normetanephrines were markedly elevated with a raised 3-methoxytyramine, while plasma metanephrines were normal. Computed tomography identified a 4.4 cm mass at the right inferolateral margin of the bladder wall. Scintigraphic imaging confirmed unifocal bladder lesion uptake with no additional metastatic lesions. Following pre-operative alpha blockade, the patient underwent a partial cystectomy. Histology confirmed a paraganglioma, and SDHB staining was lost in neoplastic cells consistent with an SDHB-related paraganglioma. Plasma normetanephrine, 3-methoxytyramine and blood pressure returned to normal postoperatively. Genetic screening identified a germline heterozygous SDHB gene variant c.723C>G. Bladder paragangliomas are a rare but important differential to consider when investigating post-micturition syncope. An extended family history should be sought and suspicion for a genetic cause should be raised, especially when the condition presents at a young age. This is the first reported case describing phaeochromocytoma or paraganglioma with the SDHB gene variant c.723C>G.LEARNING POINTSBladder paragangliomas are a rare neuroendocrine tumour which should be considered when assessing patients with haematuria and hypertension, headache, palpitations, sweating and facial pallor with micturition.This case highlights the importance of a thorough clinical history with an extended family history and examination in the setting of micturition syncope, which can rarely occur with bladder paraganglioma.Young age at presentation, a family history of phaeochromocytoma and paraganglioma (PPGL), unusual paraganglioma location, mutifocality and aggressive disease should raise the suspicion for a genetic predisposition to PPGL.

PSMA-Directed Imaging and Therapy of Salivary Gland Tumors: A Single-Center Retrospective Study.

We analyzed the diagnostic performance of prostate-specific membrane antigen (PSMA) PET/CT and the dosimetry, efficacy, and safety of 177Lu-PSMA-617 radioligand therapy (RLT) in salivary gland malignancies (SGMs). Methods: We identified 28 SGM patients with PSMA PET/CT from our database. CT and PSMA PET/CT images were evaluated separately by 3 masked readers in joint reading sessions. Pathologic findings were grouped into 6 TNM regions, and lesion-based disease extent was classified as no disease (n = 1, 4%), unifocal (n = 2, 7%), oligometastatic (n = 9, 32%), multifocal (n = 3, 11%), or disseminated (n = 13, 47%). For each region, the SUVmax of the lesion with the highest uptake was measured and the visual PSMA expression score was evaluated on a per-patient basis using PROMISE criteria. The association between PSMA expression and clinical and histopathologic markers was tested using the Student t test. Five patients underwent PSMA RLT with intratherapeutic dosimetry. Response was assessed using RECIST 1.1, and adverse events were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events. Results: Compared with CT, PSMA PET/CT demonstrated additional metastatic lesions in 11 of 28 (39%) patients, leading to upstaging of TNM and lesion-based disease extent in 3 (11%) and 6 (21%) patients, respectively. PSMA PET/CT detected CT-occult local tumor, regional lymph nodes, nonregional lymph nodes, and bone metastases in 1 (4%), 4 (14%), 2 (7%), and 4 (14%) patients, respectively; no additional lesions were detected in the other predefined regions. PSMA expression level was higher than liver in 6 patients (25%). A significantly higher SUVmax was observed in male than female patients (15.8 vs. 8.5, P = 0.007) and in bone than lung lesions (14.2 vs. 6.4, P = 0.006). PSMA RLT was discontinued after 1 cycle in 3 of 5 patients because of insufficient tumor doses. No adverse events of grade 4 or higher occurred. Conclusion: In SGMs, PSMA PET/CT demonstrated a superior detection rate and led to upstaging in about one third of patients when compared with CT. The male sex and the presence of bone metastases were associated with significantly higher PSMA expression. PSMA RLT was well tolerated, but most patients did not have more than 1 cycle because of insufficient tumor doses.

Tolerability and outcome of palliative treatment for metastatic pulmonary carcinoma in cats.

Pulmonary carcinoma is uncommon in cats and reporting of outcomes following medical treatment is limited, especially in presence of metastases. The aim of this study was to describe the outcome of cats affected by metastatic primary pulmonary carcinoma and to evaluate the tolerability of palliative treatment in this patient population. Medical records were searched for cats with a cytological or histopathological diagnosis of primary pulmonary carcinoma and evidence of metastatic disease. Cats were treated with antineoplastic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or received no systemic treatment. Cases in which thoracic CT was not performed, and those lacking definitive diagnosis by cytology or histopathology or receiving curative-intent surgery were excluded. Thirty-four cats were identified: 18 were treated with antineoplastic agents and 16 received corticosteroids, NSAIDs or no treatment. Presenting clinical signs included coughing (53%), tachypnoea (26%), gastrointestinal signs (35%) and lethargy (18%). CT scan identified metastases to the lung parenchyma in all cases and additional metastatic lesions in 10 of 34 (59%) cases; pleural effusion was detected in 11 cases (32%). The overall median survival time for all cats was 64 days [range 1-1352 days; 95% confidence interval (CI) 48-164]. Presence of respiratory signs at presentation was the only factor influencing survival in the multivariable analysis. Medical treatment was well tolerated and appeared to palliate clinical signs in cats with metastatic pulmonary carcinoma, albeit with a modest duration and short overall survival. The role and benefit of chemotherapy/antineoplastic agents versus conventional palliative drugs in this setting remains unclear.

Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients with Oligometastatic Breast Cancer: Study protocol for a randomized controlled multi-national and multi-center clinical trial (OLIGOMA)

BackgroundSeveral recent randomized therapeutic exploratory trials demonstrated improvement of progression-free survival and in some even overall survival using stereotactic body radiotherapy in patients with oligometastatic disease. However, only very few patients enrolled in these trials had breast cancer, and results from confirmatory trials are lacking. Methods/designThe OLIGOMA-trial is a randomized controlled multi-national multi-center therapeutic confirmatory trial studying the role of local ablative radiotherapy as an additive treatment in patients with oligometastatic breast cancer receiving standard systemic therapy. Patients will be randomized 1:1 to standard systemic therapy according to national guidelines with or without radiotherapy to all metastatic sites. Randomization will be stratified according to type and line of systemic therapy, which has to be determined by a multidisciplinary tumor board before enrollment. Patients with up to five metastatic lesions are eligible, including patients with up to three brain metastases (only in case of extracranial disease) and with locoregional recurrence (only in case of additional metastatic lesions). In the standard arm, palliative radiotherapy to symptomatic metastases is permitted if at least one lesion remains untreated. The co-primary endpoints are progression-free survival and quality of life. The primary hypothesis is that progression-free survival in the experimental arm will be superior to the standard arm while simultaneously demonstrating non-inferiority of quality of life at 12 weeks after randomization. Secondary endpoints are feasibility, overall survival, toxicity, quality of life and patient satisfaction. A translational sub-study with collection of ctDNA will be conducted. DiscussionThe OLIGOMA-trial will provide high level evidence on the use of and benefit from local ablative radiotherapy for patients with oligometastatic breast cancer. Trial registrationThe OLIGOMA-trial is registered at clinicialtrials.gov under the identification NCT04495309. The related information was first posted on July 31st 2020.

S2880 A Rare Cause of Melena

INTRODUCTION: Melanoma presenting in the gastrointestinal tract is commonly due to metastasis from a primary cutaneous or ocular lesion. There have been a few case reports of primary GI melanoma which is most commonly seen in the rectum and anus. We report a case of a 77 year old man who presented with GI bleeding and was found to have a primary small bowel melanoma. CASE DESCRIPTION/METHODS: A 77-year-old male presented with generalized weakness and a remote history of melena for the past week. Physical exam was unremarkable with no palpable masses or abdominal tenderness. Labs were significant for iron deficiency anemia with a hemoglobin of 8.9 from 13.1 and a ferritin of 14 ng/ml. Patient underwent bidirectional endoscopy which showed no clear source for iron deficiency anemia. A capsule endoscopy was performed, and a mass with overlying ulcerated mucosa was seen in the small bowel (Figure 1). Subsequent computed tomographic enterography demonstrated a 3.3 cm soft tissue mass in the jejunum (Figure 2). As the mass was unable to be reached endoscopically, the patient underwent laparoscopic removal of the mass, and pathology was most consistent with malignant melanoma. Histology showed solid nests of epithelioid cells with brisk mitotic activity, and immunohistochemistry staining was positive for SOX-10 (Figure 3), a marker of melanocyte differentiation. The patient underwent a skin exam showing no evidence of a cutaneous primary melanoma, and a fundoscopic exam showed no evidence of ocular melanoma. A PET scan did not identify an alternative site of primary malignancy or any other sites concerning for metastatic disease. As the patient had a solitary lesion in the small bowel without evidence of an alternative primary melanoma, the final diagnosis was primary malignant melanoma of the jejunum. At one year follow up, patient did not have any recurrence noted on imaging. DISCUSSION: While melanoma is the most common tumor to metastasize to the GI tract, small intestinal primary melanoma is extremely rare making up 2.3% of primary GI melanomas. In all cases where melanoma is found in the GI tract, a comprehensive evaluation for additional metastatic lesions and alternative primary site with a skin exam, fundoscopic exam and PET scan is indicated. Primary GI melanoma is a rare clinical entity with nonspecific symptoms that requires a high index of suspicion and a thorough workup for a primary source when diagnosed.Figure 1.: Mass with overlying ulcerated mucosa in the small bowel on capsule endoscopy.Figure 2.: 3.3 cm soft tissue mass in the jejunum on computed tomographic enterography.Figure 3.: Immunohistochemistry staining of jejunal mass was positive for SOX-10, a marker of melanocyte differentiation.

MON-451 An Unusual Case of Follicular Thyroid Cancer with Pulmonary Metastasis and Concurrent Hyperthyroidism

Introduction: Follicular Thyroid Cancer (FTC) accounts for approximately 12 % of all thyroid cancers and is the second most common cause of differentiated thyroid cancer. However, coexisting hyperthyroidism and thyroid malignancy is considered a rare event and is thought to have a prevalence of 0.21–9.0 %. We describe a compelling case of metastatic FTC initially presenting with subclinical hyperthyroidism progressing to overt hyperthyroidism.Clinical Case: An 88-year-old man with a history of prostate cancer, previous tobacco dependence, and hypertension initially presented with complaints of a chronic non-productive cough associated with unintentional weight loss and fatigue. Initial imaging included a chest CT that showed several bilateral pulmonary nodules suspicious for metastatic disease, as well as an enlarged left-sided thyroid mass, which extended from the inferior pole into the mediastinum. FDG PET/CT showed avid disease identified in the lung. CT-guided lung biopsy was performed, and histopathology revealed FTC. Thyroid function tests (TFTs) revealed a Tg level of 1427 (0.00–33.70), TgAb <1.0 (< 13.6), TSH 0.05 (0.40–4.50), FT4 1.1 (0.8–1.8) and FT3 3.4 (2.3–4.2). Biochemical testing was consistent with subclinical hyperthyroidism. Neck ultrasound showed bilateral thyroid nodules, the largest located on the left mid-pole measuring 3.4 x 3.2 x 3.7 cm. He underwent a whole-body I-131 diagnostic scan, which showed intense uptake of the radionuclide within the thyroid gland, more evident on the left, but additional metastatic lesions elsewhere in the visualized body were not possible. TFTs were repeated, which showed a TSH of 0.01, FT4 of 2.0, and FT3 of 6.4. He was subsequently started on methimazole daily and eventually became euthyroid. Due to advanced age, significant mediastinal extension, and lung metastasis, the patient was not a candidate for surgical resection and treatment with a targeted tyrosine kinase inhibitor. He ultimately opted for an observational approach.Conclusion: Although metastatic FTC carries a poor prognosis, concurrent hyperthyroidism is thought to be associated with a more aggressive disease course and higher mortality compared to differentiated thyroid cancers in euthyroid patients.Sources: 1. Pazaitou-Panayiotou, K., Perros, P., Boudina, M., Siardos, G., Drimonitis, A., Patakiouta, F., & Vainas, I. (2008). Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience, European Journal of Endocrinology, 159(6), 799–803.2. Benjamin Momo Kadia, Christian Akem Dimala, Ndemazie Nkafu Bechem, Desmond Aroke. BMC Res Notes. 2016; 9: 369.3. Parameswaran R, Shulin Hu J, Min En N, Tan WB, Yuan NK. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. Ann R Coll Surg Engl. 2017;99(2):151–154.

Clinical utility of 18F-FDG PET/CT for patients with recurrent head and neck squamous cell carcinoma

Background: The accurate detection of distant metastases can facilitate appropriate treatment planning for patients with recurrent head and neck squamous cell carcinoma (HNSCC).Objectives: We evaluated the role of 18F-FDG PET/CT for distant metastasis diagnosis and survival prediction in patients with recurrent HNSCC.Materials and methods: This study included 95 consecutive patients with recurrent HNSCC and salvage treatments. McNemar’s test was used to compare the detection of distant metastasis at recurrence using 18F-FDG PET/CT and contrast-enhanced chest and neck CT, and bone scintigraphy.Results: Thirty-two patients (34%) had distant metastases at recurrence. The sensitivity, specificity, accuracy, and positive and negative predictive values of 18F-FDG PET/CT for detecting chest and bone metastases were comparable to those of conventional imaging (p > .1). However, 18F-FDG PET/CT detected two additional distant metastatic lesions. After controlling for clinicopathological factors, a recurrent lesion with maximum standardized uptake value (SUVmax) >8.7 was identified as an independent predictor of poor overall survival (p = .001).Conclusions and significance: 18F-FDG PET/CT or conventional imaging is comparable with regard to detecting distant metastases of recurrent HNSCC. However, 18F-FDG PET/CT may detect additional metastatic lesions in unusual distant sites and the recurrent lesion SUVmax may predict patient survival after salvage treatments.

Significance of incidental intra-articular and peri-articular FDG avid foci on PET/CT.

Positron emission tomography/computed tomography (PET/CT) is a useful imaging adjunct in patients with sarcoma. Intra-articular and peri-articular 18F-fluoro-2-deoxy-D-glucose (FDG) avid lesions are often discovered incidentally. To describe the etiology, appearance, and standardized uptake values (SUV) of incidentally detected FDG avid intra-articular and peri-articular foci in patients with sarcoma. The institutional sarcoma database between November 2011 and November 2016 was retrospectively reviewed. Patients were included if a PET/CT scan was performed and an FDG avid intra-articular or peri-articular focus was found that was distinct from the primary sarcoma. The majority of FDG avid foci represented benign, non-physiologic conditions such as osteoarthritis, enthesopathy, bursitis, and post-surgical changes. Six patients each had radiographic features consistent with tenosynovial giant cell tumor (TSGCT) and metastatic disease, respectively. Lower SUV, bilateral findings, and the absence of metastatic disease elsewhere were associated with benign etiologies. There was a statistically significant difference between the mean SUV measured in patients with TSGCT and those with benign, non-physiologic conditions ( P < 0.001). The difference between the benign, non-physiologic cohort and the cohort with widespread metastatic disease did not reach statistical significance ( P = 0.07). In patients with soft-tissue or osseous sarcomas, isolated FDG avid intra-articular or peri-articular foci without additional metastatic lesions likely represent benign processes. Isolated intra-articular or peri-articular foci with significantly elevated SUV measurements were favored to represent TSGCT in this series.

The Role of 18F FDG PET/CT in Clinical Management of Breast Cancer; Additional Value Over Conventional Imaging Modalities

Background: The aim of the present study was to investigate the potential improvement in detection rate of nodal and distant metastasis and the resultant impact on clinical management by PET-based diagnostic work up in comparison with conventional imaging modalities in various clinical settings in patients with breast cancer. Methods: Of a total 256 patients with breast cancer who were referred to PET/CT division, MasihDaneshvari Hospital between May 2013 and Mar. 2016, 123 cases were included. Definitely-positive PET/CT findings in primary site as well as N1 (level I, II ipsilateral axillary nodes), N2 (ipsilateral internal mammary), N3 (ipsilateral internal mammary+ level I, II ipsilateral axillary, ipsilateral level II axillary, ipsilateral supraclavicular node) and distant metastasis (distant node and viscera) and related impact on clinical management (upstaging or downstaging) were retrospectively identified from the report archive and then compared with the results of baseline imaging modalities including CT scan, sonography, bone scan, C-X ray, MRI, MRM and mammography obtained from patient medical records. The most typical imaging pattern was considered as the reference standard. Indeterminant and equivocal PET positive lesion were not included in the study. Results: Fourteen (11.38%) and 109 (88.62%) out of 123 patients were referred for staging and restaging/recurrence/surveillance, respectively. Mean age were 51.42 (34 - 62) and 52.66 (29 - 79) for staging and restaging groups, respectively. In staging group, 18 F FDG PET/CT recognized definitely positive additional nodal involvement in 21.4% of patients all of them related to the supraclavicular level and hence result in change N staging to N3. Additional metastatic lesions on a per lesion-basis and a per organ-basis were identified as 28.6% and 14.3%, repsectively. A significant change in patient management occurred in 42.9% (35.7% upstaging, 7.2% down staging). In restaging group, locoregional detection rate in biopsy proved recurrence was 100%. Additional nodal detection and the resultant change in N staging were 29.6% and 28.7%, respectively. Supraclavicular node detection contribute in 53.12% of overall change in N staging followed by axillary node and internal mammary equally (15.62%). Additional metastatic lesions on a per lesion-basis and per organ-basis were identified in 53.2% and 44%, respectively. Ultimate change in patients management was found in 42.9%. Conclusions: 18 F FDG PET/CT is a valuable imaging tool in initial and subsequent treatment strategy in patients with breast cancer by providing additional nodal and distant metastasis and may have the promising future potential to be as the imaging modality of choice for accurate assessment of disease extension in breast cancer in routine clinical practice.

P1.02-018 Osteosarcomatous Differentiation in the Rebiopsy Specimens of Patients Harboring Pulmonary Adenocarcinoma with EGFR-TKI Resistance

Histological transformation including small cell carcinoma and epithelial to mesenchymal transition (EMT) is one of the discovered mechanisms of the acquired resistance to EGFR-TKI. We report two cases of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) resistant pulmonary adenocarcinoma associated with EMT features that showed osteosarcomatous differentiation in rebiopsy specimens. We identified two patients with primary lung adenocarcinoma that showed osteosarcomatous transformation on second biopsy (n = 60) between 2010 and 2016. Histomorphologic features and EGFR mutation results were compared between initial and second biopsy samples. Case 1 A 55-year-old female, non-smoker presenting chronic cough was found to have pulmonary adenocarcinoma harboring EGFR exon 19 deletion mutation with disseminated intrapulmonary metastasis. After 1 year of gefinitib treatment, radiologic evaluation showed left iliac metastases with extraosseous ossification. Case 2 A 58-year-old man who had undergone right upper lobectomy of the lung was diagnosed as adenocarcinoma with pT1N0M0 harboring an EGFR exon 19 deletion mutation. Three years after surgery, metastatic lesions developed in the right lower lobe and pleura. After 15 months of conventional chemotherapy, 2nd biopsy for the pulmonary lesion confirmed T790M mutation and additional metastatic lesions found in T2 and T5 vertebral bodies were removed by surgical curettage. Rebiopsy of the metastatic bone lesions of these two patients showed metastatic adenocarcinoma merging with poorly differentiated sarcomatous components. Remarkably, the spindle shaped sarcomatous tumor cells produced ill-defined eosinophilic lace-like osteoid. These osteoid components were closely associated with the tumor cells and deposited as disorganized features. The sarcomatous neoplastic cells intermingled with osteoid demonstrate unequivocal features of malignancy, which is different from reactive osteoid or callus formation. EGFR mutation status were same from that of primary lung specimen and IHC showed vimentin expression and decreased E-cadherin (EMT feature). To the best of our knowledge, this is the first report to describe pulmonary adenocarcinoma with osteosarcomatous differentiation in rebiopsy specimens of EGFR-TKI resistant patients. As the evaluation of metastatic sites for rebiopsy were bone lesions in both patients, the role of the tumor microenvironment may support the transformation from adenocarcinoma to osteosarcomatous phenotype. A few previous studies suggested that a bone environment is essential for osteosarcoma development from transformed mesenchymal stem cells. Our findings suggest that the differences of the intrinsic nature between epithelial and osteosarcomatous mesenchymal cancers may be the cause of the acquired resistance of EGFR-TKI.

Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma

Solitary bone and brain metastasis in a patient with papillary thyroid carcinoma mimicking cavernous angioma

It Is Time to Reevaluate the Management of Patients With Brain Metastases

There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting.

Clinical Utility of 18F-FDG PET/CT Concurrent with 131I Therapy in Intermediate–to–High-Risk Patients with Differentiated Thyroid Cancer: Dual-Center Experience with 286 Patients

Patients with differentiated thyroid carcinoma (DTC) are treated with (131)I therapy after total thyroidectomy or surgical resection of recurrent tumor. However, some recurrent DTC lesions are not iodine-avid, which affects further treatment planning. The aim of this study was to evaluate the clinical benefit of (18)F-FDG PET/CT performed concurrently with (131)I therapy in DTC patients with intermediate to high risk. We retrospectively enrolled 286 DTC patients at 2 Korean medical centers who comprised 2 different patient groups: 28 patients who underwent adjuvant (131)I treatment after curative surgical resection of recurrent tumor and 258 patients with intermediate to high risk who underwent (131)I ablation after total thyroidectomy. (131)I therapy and (18)F-FDG PET/CT scanning were performed on the same day. Administration of l-thyroxine was withheld from all enrollees for 4 wk before (131)I treatment. In 39 patients (14%), (18)F-FDG PET/CT detected additional recurrent or metastatic lesions that were not detected on the posttherapy (131)I scan, and the treatment plan was changed for 30 patients (10%) based on such findings. Among the 28 patients receiving (131)I treatment after resection of recurrent tumor, PET/CT detected additional lesions in 46%, and treatment was changed in 43%. Assessing a subgroup of stage T3-T4N1 patients with tumor size > 2.0 cm, among 258 patients undergoing (131)I ablation after total thyroidectomy, we found that 25% had additional positive PET/CT results, and treatment changed for 17%. In contrast, 8% of stage T3-T4N1 patients with tumor size ≤ 2.0 cm, 6% of stage T1-T2N1 patients, and 3% of stage T3-T4N0 patients had additional positive PET/CT findings. (18)F-FDG PET/CT performed concurrently with (131)I therapy detected additional lesions in 14% of DTC patients and was particularly helpful for detecting additional lesions in patients undergoing (131)I therapy after resection of recurrent tumor or in stage T3-T4N1 patients with tumor size > 2.0 cm.

Outcome and Prognostic Factors After Adrenalectomy for Patients with Distant Adrenal Metastasis

The purpose of this study was to describe a single-institution experience with adrenal metastasectomy and to elucidate factors that may bear prognostic significance. This is a single-center, retrospective review of patients with adrenal metastasis who underwent adrenalectomy performed with curative intent between 2000 and 2012. The Kaplan-Meier method was used to evaluate overall survival from time of adrenalectomy to death or last follow-up. Primary endpoint was death from any cause. Clinical variables were examined for association with survival. The study included 62 patients with mean age of 60 (±12) years; 55% (34 of 62) were male, 85% (53 of 62) presented with isolated adrenal metastasis, and 82% (51 of 62) had metachronous disease with median disease-free interval (DFI) of 22months (range, 6-217months). Non-small cell lung cancer (NSCLC) was the most common primary comprising 50% of cases. Median survival for the study population was 30months (range, 1-145months) and 5-year survival was 31%. Patients with NSCLC had significantly shortened survival compared with non-NSCLC with median and 5-year survival of 17 versus 47months and 27% versus 38%, respectively (p=.033). Synchronous metastasis (p=.028) and DFI<12months (p=.038) were also associated with worse survival outcome, though male gender (p=.69) and oligometastatic disease (p=.62) were not. Adrenal metastasectomy resulted in median survival of 30months and 5-year survival of 31%. Shorter survival was associated with lung primary, short disease-free interval, and synchronous metastasis, but not with the presence of oligometastatic disease provided that the primary cancer and additional metastatic lesions were adequately controlled and amenable to resection.

Osseous metastases of gastro- entero - pancreatic neuroendocrine tumours

SummaryAim: Peptide receptor radionuclide therapy with 177Lu-octreotate is an effective treatment option for metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET) and allows intratherapeutic imaging through a 177Lu-octreotate scan (LuS). The diagnostic value of this treatment scan is not yet established. This study aims to compare the sensitivity of LuS and bone scintigraphy (BS) regarding bone metastases and investigate potential implications of functional imaging results. Patients, methods: We retrospectively analyzed 29 consecutive GEP NET patients with bone metastases and baseline BS treated with 177Lu-octreotate. A semi-quantitative scoring system was used for the comparative evaluation. Treatment outcome (time-to-progression of bone metastases) was correlated with the intra-individual imaging discrepancy (Kaplan- Meyer curves, log-rank test, p &lt; 0.05). Results: In 19 of 29 patients (65.5%) LuS was superior (LuS &gt; BS), whereas in 10 patients (34.5%) both modalities were comparable. BS showed no additional (LuS-negative) metastatic bone lesions in our cohort. None of the investigated baseline characteristics was associated with Imaging discrepancy. On the other hand, functional imaging discrepancy had no impact on treatment response (p = 0.43) or time-to-progression (p = 0.92). Conclusions: Intra-therapeutic 177Lu-octreotate imaging is superior over bone scintigraphy for detection of bone metastases in GEP NET. BS may help to distinguish osseous from non-osseous localization. The presence of an osteoblastic correlate in BS seems to have no impact on therapeutic outcome

Metastatic Papillary Thyroid Carcinoma to the Maxilla: Case Report and Literature Review

Metastatic tumors to the oral cavity are uncommon and a thyroid origin is considered exceedingly rare. A case of metastatic papillary thyroid carcinoma (PTC) presenting as a painful swelling in the right posterior maxilla of a 63-year-old male is reported here. The patient had been diagnosed with PTC 2 years ago and treated with thyroidectomy and radioactive iodine treatment. Radiographically, the metastatic lesion presented as a poorly-defined radiolucent lesion around an impacted maxillary third molar in the right maxilla. Histopathologic examination revealed features of PTC which was immunohistochemically positive for pancytokeratin, keratin 19 and thyroglobulin. Imaging studies revealed the presence of residual maxillary and neck disease as well as additional metastatic lesions in the sternum, ribs, and left tibia. A thorough review of the English language literature revealed only 36 previously published cases of thyroid cancer metastases to the oral cavity, the demographic and clinicopathologic features of which are summarized.