Jejunal Adenocarcinoma with Pulmonary Hilar Lymph Node Metastasis Initially Misdiagnosed as Pulmonary Hilar and Mediastinal Tumors

Mediastinal Mass with Unusual Etiology.

Nodal Involvement at the Time of Pulmonary Metastasectomy: Experiences in 245 Patients

The small intestine makes up 75% of the length of the alimentary tract, however, small intestinal tumors constitute less than 5% of gastrointestinal tumors. Of small intestinal tumors, around one third are aggressive adenocarcinomas with poor outcome (5-year survival rate is approximately 30%). Reasons for their rarity are still unclear. Predisposing factors include Crohn´s disease, celiac disease, hereditary genetic syndromes such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), and dietary factors. Due to the low incidence of small intestinal adenocarcinomas (SIAs), the number of genetic studies remains insufficient. Since there are limited data available to guide the therapeutic decisions, our aim is to characterize the somatic mutational landscape of SIAs in a population-based material using exome sequencing. We collected information on all patients diagnosed with SIA in Finland between the years 2004-2011 utilizing the Finnish Cancer Registry. This registry maintains a nation-wide database on all cancer cases diagnosed in Finland since 1953. From these we selected all cases with 1) confirmed small intestinal primary tumor, 2) available tumor material, and 3) the tumor content of at least 50%. In order to focus solely on small intestinal tumors, we excluded tumors of the papillary region since they might also have arisen from the pancreas or the biliary tract. Altogether 107 tumors representing all three parts of the small intestine were selected for exome sequencing. The tumor data was filtered against the ExAC and SISU databases to remove germline variations. In addition, Sanger sequencing of the corresponding normal tissue will be used to verify the somatic origin of the most interesting observed mutations. The data analysis is ongoing. The average number of mutations in a tumor was 358 (range 40 - 4,166). Preliminary results show that the most frequently mutated known cancer genes were TP53 (42%) and KRAS (31%). We will identify all the most frequently mutated genes, compare the mutational patterns between the three different sections of the small intestine, and further characterize their similarities to gastric and colorectal adenocarcinomas. We will also analyze the association between the discovered mutations and patients’ survival time. This comprehensive characterization of the molecular basis of SIAs will provide better insight on how these tumors arise and possibly how they should be treated. Citation Format: Ulrika A. Hänninen, Riku Katainen, Jiri Hamberg, Jukka-Pekka Mecklin, Linda Forsström, Esa Pitkänen, Netta Mäkinen, Lauri A. Aaltonen. Somatic exomic landscape of small intestinal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4379. doi:10.1158/1538-7445.AM2017-4379

Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement. The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection. The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor. N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.

Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture.We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.

Persistent Positron Emission Tomography–Positive Liver Lesions After Successful Chemotherapy in Mediastinal Seminoma

8565 Background:Over the past 25 years, 95 of 210 patients (pts) under 20 years of age were subjected to surgical procedures for resection of pulmonary metastases (PM). This included completion pneumonectomy (CPN) in five pts and removal of the RML and RLL in another pt. Interval from diagnosis to detection of PM ranged from 1.5 to 2 yrs. Interval from removal of the last PM to CPN ranged from 1.7 to 3 yrs. Pts were considered candidates for CPN provided the following criteria were met: 1) Despite responses, all PM could not be eradicated with chemotherapy; 2) PM were always confined to one lung; 3) Primary tumor was extirpated; 4) No evidence of extra PM; 5) Existing PM could not be extirpated by wedge resection or lobectomy; 6) Pulmonary function would be adequate after CPN. Methods:Pulmonary function tests obtained. CPN performed. After CPN additional chemotherapy administered. Four pts were also treated with radiation therapy (45–50 Gy) to sites of suspected residual microscopic disease with methotrexate to potentiate radiotherapeutic effect. Results:No significant post operative complications. Four of six pts are alive and disease free (10.5, 4.5, 1, and 0.3 yrs) post CPN. Cause of death: One pt: inoperable left paraspinal mass with the remaining lung clear. Second pt: tumor invasion into hilar lymph nodes and pericardium. Conclusions:Long term survival following CPN appears attainable in some pts who meet the criteria described above. Important indications appear to be inability to eradicate PM by chemotherapy and inability to perform wedge resection or lobectomy. However, the long surveillance period with continual absence of disease in the contralateral lung, i.e. 3.2–5 yrs from diagnosis, was probably the major eligibility criterion. No significant financial relationships to disclose.

Tumor Infiltrated Hilar and Mediastinal Lymph Nodes are an Independent Prognostic Factor for Decreased Survival After Pulmonary Metastasectomy in Patients With Renal Cell Carcinoma

Surgery has become a recognized therapeutic means in selected patients with pulmonary metastases from colorectal origin. We reviewed our experience in the surgical treatment of 153 patients with pulmonary colorectal metastases and investigated factors affecting survival. A retrospective analysis of the records of all patients (n = 153) with pulmonary metastases from colorectal cancer who underwent thoracotomy between 1978 and 2003 at a single surgical center was performed. One hundred fifty-three patients with pulmonary metastases from colon (n = 61) or rectal (n = 92) cancer underwent 180 thoracotomies. The 2- and 5-year probabilities of survival after the first thoracotomy were 64% and 37%, respectively. Sex, age, site, International Union Against Cancer stage of the primary tumor, prethoracotomy carcinoembryonic antigen level, size of metastases, and previous resection of hepatic metastases were not found to be statistically significant prognostic factors. Number of metastases (solitary vs. multiple), mode of operation (wedge vs. anatomical resection), disease-free interval (DFI; > 36 months), negative hilar or mediastinal lymph node status, resection margin > 10 mm, and administration of intraoperative blood substitution were predictors of a longer survival duration by univariate analysis, but only number of metastases (P = .019), mode of operation (P = .004), DFI (P = .027), and intraoperative blood substitution (P = .002) were identified as independent prognostic factors by multivariate analysis. Pulmonary resection for metastases from colorectal cancer is safe and results in long-term survival in selected patients. Single metastases, anatomical resection, intraoperative blood substitution, and DFI > 36 months seem to be the most reliable predictors of survival.

Background: Primary adenocarcinomas of the small intestine are rare, and the genetic mechanisms involved in their carcinogenesis remain unclear. Aim: To examine the expression of candidate proteins in small intestinal...

To study angiogenesis of axillary lymph node metastases (including micrometastatic foci and metastatic tumors) in breast carcinoma and the relationship between microvessel density (MVD) and metastasis. Thirty-seven breast cancer tissues and 121 metastatic axillary lymph nodes were collected from breast cancer patients and studied immunohistochemically. MVD was counted by means of microvideo system under 100x magnification. The diameter of each micrometastasis was measured with a micrometer. The mean diameter of 13 micrometastatic foci was 210 +/- 37 microns. No blood vessel formation was found. MVD of the primary tumor and that of metastatic tumor in the axillary lymph node was 93.8 +/- 21.8 and 89.3 +/- 18.4, respectively (P > 0.05). The distribution of microvessels of the metastatic tumor in the lymph node and that of the primary tumor was similar, being higher at the periphery than at the center. Micrometastatic foci of breast carcinoma in the axillary lymph node do not have new blood vessel formation. Their further growth, however, depends on neo-angiogenesis. Treatment based on inhibition of angiogenesis may be efficacious in the prevention of micrometastatic foci from developing into metastatic tumor in lymph node.

In systemic hyper-inflammation, as in severe COVID-19 disease, there are pronounced disorders of the hematological and lymphatic systems with prognostically relevant hemophagocytosis of the bone marrow. The current work aimed to address the importance of hemophagocytosis in the lymph nodes of patients with severe COVID-19 disease. From 28 patients who died of severe COVID-19 infection, samples of the vertebral bone marrow and lymph nodes from the cervical, hilar, para-aortic, mesenteric and inguinal locations were morphologically and immunohistologically (CD163, CD68, CD61, CD71, CD3, CD20, CD138) examined for the possible presence of hemophagocytosis. In the single-center study at the University Hospital Jena, a total of 191 hemophagocytes were found in the bone marrow and a total of 780 hemophagocytes in the lymph nodes in a standardized area of 21,924 mm2 per tissue sample. With 370 hemophagocytes, hilar lymph nodes were most frequently affected (370/780; 47.44%; 95%-CI: [43.94, 50.95]), followed by cervical lymph nodes (206/780; 26.41%; 95%-CI: [23.41, 29.59]), para-aortic lymph nodes (125/780; 16.03%; 95%-CI: [13.58, 18.73]) and inguinal/mesenteric lymph nodes (79/780; 10.13%; 95%-CI: [8.155, 12.4]). Based on the standard area (21,924 mm2), the difference in the number of hemophagocytes in the bone marrow and in the hilar lymph nodes was statistically significant (p < 0.05), while this did not apply to the lymph nodes from the other locations. In fatal COVID-19 disease, hemophagocytosis is particularly found in the hilar lymph nodes and is therefore a better indicator of the severity of the disease than hemophagocytosis in the bone marrow. The findings provide some evidence for the concept of compartmentalized human host responses to life-threatening infections.

To evaluate the usefulness of a new computed tomographic (CT) criterion for diagnosing hilar lymph node metastases on the basis of the margin between hilar interstitium and lung parenchyma. The morphology of normal and metastatic hilar nodes was analyzed in seven inflated and fixed human lung specimens. Thin-section, incremental, dynamic CT was then performed preoperatively in 95 patients with lung cancer, and the margins of peribronchovascular hypoattenuated areas were evaluated in 22 of the patients with normal hila. CT-pathologic comparisons were performed at 179 locations where interstitium touched lung parenchyma. The comparison was based on a new CT criterion in which convex interstitial margins indicate nodal metastases. The margins of the interstitia with normal nodes were concave or straight at 94.8% (183 of 193) of the contact sites in the six normal specimens and at 97.3% (436 of 448) of the contact sites on CT scans, whereas the margins of the interstitia with abnormal nodes were convex at 94.7% (54 of 57) of the contact sites in the abnormal specimen. Sensitivity, specificity, and accuracy of three reviewers who used the new criterion were 87.3%, 88.3%, and 88.1%, respectively. The new CT criterion is useful for the diagnosis of hilar node metastases in lung cancer.

Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases

65-Year-Old Man With Persistent Fever