Ten-year follow-up outcomes of limited resection trial for radiologically less-invasive lung cancer.

BACKGROUND: The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. METHODS: We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2 cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. RESULTS: Our patients, with a median age of 62 years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9 months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. CONCLUSIONS: Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5 years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5 years after surgery.

Evaluation of pancreatic cancer specimens for comprehensive genomic profiling.

Inadequate specimen quality or quantity hinders comprehensive genomic profiling in identifying actionable mutations and guiding treatment strategies. We investigated the optimal conditions for pancreatic cancer specimen selection for comprehensive genomic profiling. We retrospectively analyzed 213 pancreatic cancer cases ordered for comprehensive genomic profiling and compared results from pancreatic biopsy, liver biopsy of pancreatic cancer metastases, pancreatectomy, liquid, and nonliver metastatic organ specimens. We examined preanalytical conditions, including cellularity (tumor cell count/size). The successfully tested cases were those that underwent comprehensive genomic profiling tests without any issues. The successfully tested case ratio was 72.8%. Pancreatic biopsy had the highest successfully tested case ratio (87%), with a high tumor cell percentage, despite the small number of cells (median, 3425). Pancreatic biopsy, liver biopsy of pancreatic cancer metastases, and non-liver metastatic organ had higher successfully tested case ratios than that for pancreatectomy. Liver biopsy of pancreatic cancer metastases and pancreatectomy cases with tumor size (mm2) × tumor ratio (%) > 150 and >3000, respectively, had high successfully tested case ratios. The success of comprehensive genomic profiling is significantly influenced by the tumor cell ratio, and pancreatic biopsy is a potentially suitable specimen for comprehensive genomic profiling.

Bone marrow adipocytes induce cancer-associated fibroblasts and immune evasion, enhancing invasion and drug resistance.

Bone metastasis occurs frequently in cancer patients. Conventional therapies have limited therapeutic outcomes, and thus, exploring the mechanisms of cancer progression in bone metastasis is important to develop new effective therapies. In the bone microenvironment, adipocytes are the major stromal cells that interact with cancer cells during bone metastasis. However, the comprehensive functions of bone marrow adipocytes in cancer progression are not yet fully understood. To address this, we investigated the role of bone marrow adipocytes on cancer cells, by focusing on an invasive front that reflects the direct effects of stromal cells on cancer. In comprehensive histopathological and genetic analysis using bone metastasis specimens, we examined invasive fronts in bone metastasis and compared invasive fronts with adipocyte-rich bone marrow (adipo-BM) to those with hematopoietic cell-rich bone marrow (hemato-BM) as a normal counterpart of adipocytes. We found morphological complexity of the invasive front with adipo-BM was significantly higher than that with hemato-BM. Based on immunohistochemistry, the invasive front with adipo-BM comparatively had a significantly increased cancer-associated fibroblast (CAF) marker-positive area and lower density of CD8+ lymphocytes compared to that with hemato-BM. RNA sequencing analysis of primary and bone metastasis cancer revealed that bone metastasized cancer cells acquired drug resistance-related gene expression phenotypes. Clearly, these findings indicate that bone marrow adipocytes provide a favorable tumor microenvironment for cancer invasion and therapeutic resistance of bone metastasized cancers through CAF induction and immune evasion, providing a potential target for the treatment of bone metastasis.

Genetic analysis of low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma.

PURPOSE: Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear. METHODS: We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC. RESULTS: Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms. CONCLUSION: Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.

Histological findings of thyroid cancer after lenvatinib therapy.

AIMS: Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy. METHODS AND RESULTS: We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues. CONCLUSIONS: Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.

[Spontaneous remission of primary breast diffuse large B-cell lymphoma].

A 71-year-old woman became aware of a 25-mm mass in her right breast as identified by her previous doctor. Needle biopsy findings suggested malignant lymphoma, and she was referred to our hospital for further evaluation. She was diagnosed with diffuse large B-cell lymphoma (DLBCL) at our hospital. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value; 10.3), with the mass localized in the right breast, but magnetic resonance imaging findings revealed that the mass had shrunk to 10 mm. Needle biopsy was repeated in our hospital, and lymphoma cells were absent. Two months later, CT scan revealed complete disappearance of the mass, and, since then, the patient has been free of recurrence. Although there are reports of spontaneous remission of nonHodgkin's lymphoma, it is rare in the case of high-grade B-cell lymphoma. The mechanism of spontaneous remission is unclear; however, advancing age, localized stage, activated B-cell (ABC) or nongerminal center B-cell (GCB) type, and a history of infection are the associated factors. The findings from this case suggest that DLBCL can be cured without therapeutic intervention; however, careful followup may be needed.

[Metastatic Tumor of the Uterine Cervical Cancer Occurred in the Infratemporal Fossa].

A 46-year-old woman presented with discomfort in her right lateral gaze, right-sided headache, and facial numbness 17 days after concurrent chemoradiotherapy(CCRT)for a Stage ⅢB cervical cancer. The initial imaging investigations, maxillofacial and otolaryngology reviews did not reveal a diagnosis. After 54 days of CCRT, her symptoms deteriorated. Magnetic resonance imaging(MRI)showed a tumor in the right infratemporal fossa and its biopsy confirmed a metastatic cervical cancer. In view of the rapid deterioration and the potential visual loss, palliative intensity-modulated radiotherapy(IMRT) was given. Although the symptoms improved temporarily, multiple metastases were subsequently found. Despite chemotherapy, the patient died 11 months after developing the symptoms of infratemporal fossa metastasis.

Machine learning-based image analysis for accelerating the diagnosis of complicated preneoplastic and neoplastic ductal lesions in breast biopsy tissues.

PURPOSE: Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis. METHODS: Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. RESULTS: The AI-based image analysis provided the following area under the curve values (AUC): normal lesion versus DCIS, 0.9902; DCIS versus comedo DCIS, 0.9942; normal lesion versus CCL, 0.9786; and UDH versus DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the gradient-weighted class activation mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. CONCLUSIONS: These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.

[Clinical Application of Gemcitabine plus Cisplatin plus Bevacizumab Combination Chemotherapy for Ovarian Clear Cell Carcinoma].

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.

[Efficacy of Olaparib Treatment for Platinum-Sensitive Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancers].

We reviewed our clinical experience of olaparib treatment for patients with platinum-sensitive recurrent ovarian, fallopian tube, and peritoneal cancer. Of the 10 cases, the primary sites of cancer were the ovaries, fallopian tubes, and peritoneum in 7, 1 and 2 cases, respectively. The median period of treatment administration was 10 months. The observed Grade 3 or 4 adverse events as per the Common Terminology Criteria for Adverse Events version 4.0 were: anemia, leukopenia and neut r openia in 4, 4 and 3 cases, respectively. Eight cases needed treatment to be interrupted, and 5 cases required a reduction in dose. Three patients were treated for more than 12 months, while the others had to discontinue due to disease progression. However, none of the patients had to discontinue treatment due to adverse events. Therefore, it appears that olaparib can be safely used despite some patients requiring a withdrawal or reduction in treatment.

Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma.

Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for α-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type-nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary-predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P < 0.001). Univariate and multivariate analyses showed that adenocarcinomas with the fetal-type component had a significantly lower overall survival rate than the other histological subtypes, except for the micropapillary-predominant subtype. Our study demonstrated that adenocarcinomas with the fetal-type component had a poor prognosis that was comparable to that of micropapillary adenocarcinoma. The presence of the high-grade fetal adenocarcinoma component in lung adenocarcinomas is an important prognostic marker.

[A Case of Liver Metastasis 14 Years after Total Gastrectomy for Advanced Gastric Cancer].

We report a rare case of liver recurrence of gastric cancer 14 years and 3 months after curative gastrectomy. An 81-yearold man underwent total gastrectomy, D2 lymphadenectomy, Roux-en-Y reconstruction, and cholecystectomy for advanced gastric cancer in November 2002. H e was diagnosed pathologically with M, Type 5, 53×42 mm, tub2>tub1, pT4a, ly2, v2, pN1, pPM0, pDM0, M0, pStage ⅢA(JGCA 15th). Postoperative adjuvant therapy was not administered. He was followed up for 5 years after surgery without adjuvant therapy, and he did not exhibit recurrence. In February 2017, he experienced difficulties in swallowing and visited our hospital. Abdominal contrast-enhanced CT showed an 8×5 cm liver tumor in the lateral segment. Part of the tumor protruded to outside of the liver, and the tumor invaded and pushed the jejunum in the Roux limb. We performed liver biopsy and diagnosed him with liver metastasis of recurrent gastric cancer. Late relapse after gastrectomy, especially after 10 years or more, is very rare.

Risk factors associated with the progression and metastases of hindgut neuroendocrine tumors: a retrospective study.

BACKGROUND: The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. However, the mechanisms underlying progression and metastasis of hindgut NETs are unclear. A retrospective study was conducted to elucidate these mechanisms. METHODS: Clinicopathological data of cases of hindgut NET between April 1996 and September 2015 were analyzed, retrospectively. Patients with neuroendocrine carcinoma were excluded. Formalin-fixed paraffin-embedded tissues of hindgut NET cases were subjected to detailed morphometric and immunohistochemical analyses. Statistical analyses were performed using the non-parametric Mann-Whitney U test, Spearman's correlation coefficient, and chi-squared test. Multivariate logistic regression analysis was conducted as appropriate for the data set. RESULTS: Fifty-six hindgut NET cases were considered. Microvessel density and lymphatic microvessel density were identified as significant risk factors for venous and lymphatic invasion. There was a positive correlation between microvessel density and the maximum tumor diameter. Multivariate logistic regression analysis revealed that the maximum tumor diameter alone was an independent predictor of lymph node metastasis, whereas lymphovascular invasion and MVD was not the predictor of lymph node metastasis. There were no significant correlations between the Ki-67 labeling index and any of the parameters evaluated including age, sex, the maximum tumor diameter, venous invasion, lymphatic invasion, microvessel density, lymphatic microvessel density, and lymph node metastasis. CONCLUSIONS: Angiogenic mechanisms may play important roles in the progression of hindgut NET. Otherwise, the maximum tumor diameter alone was an independent predictor of lymph node metastasis in hindgut NETs. Moreover, our study raises the question of whether the presence of lymphovascular invasion, in endoscopically obtained hindgut NET tissues, is an absolute indication for additional surgery or not.

[A Case of Bilateral Pneumothorax after Chemotherapy for Uterine Leiomyosarcoma with Multiple Lung Metastases].

We encountered a case of uterine leiomyosarcoma with multiple lung metastases. The patient was a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy with gemcitabine and docetaxel. After 1 cycle of chemotherapy, the lung metastasis was reduced, but at the same time, she developed bilateral pneumothorax. Chemical pleurodesis using talc was performed. The lungs were expanded and stabilized in 7 days. After 5 cycles of chemotherapy were administered, no recurrence of pneumothorax and adverse effects were observed.

Pericardial ectopic thymoma presenting with cardiac tamponade: report of a case.

Ectopic thymoma arising from organs other than the thymus, such as the neck, trachea, thyroid, lung and pericardium, is rare. To date, there have been only seven other cases of pericardial thymoma reported in the English literature. We herein report a case of pericardial ectopic thymoma that presented with cardiac tamponade. A 72-year-old Japanese male noticed body weight gain and leg edema. Chest computed tomography (CT) revealed pericardial effusion and an irregularly shaped mass in the pericardial space compressing the right atrium. He was considered to have cardiac tamponade due to a paracardiac tumor that developed following acute cardiac failure. The intraoperative frozen diagnosis was thymoma. Pericardectomy of the thickened pericardium, tumorectomy and thymectomy via a median sternotomy were performed. The final pathological diagnosis was pericardial ectopic thymoma associated with constrictive pericarditis. The differential diagnosis and complete resection of mediastinal tumors such as this rare case of thymoma are important to obtain a better prognosis, as patients with such tumors often present in a state of shock.

[A Case of Pneumocystis Pneumonia during Chemotherapy for Recurrent Ovarian Cancer].

A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.

A case of an unreported point mutation in promoter 1B of the adenomatous polyposis coli gene, which is responsible for gastric adenocarcinoma and proximal polyposis of the stomach.

A 35-year-old woman of Asian descent with epigastralgia was referred to our hospital. Esophagogastroduodenoscopy revealed gastric cancer in the upper body and carpeting fundic gland polyposis in the fornix and body. Computed tomography revealed no metastases. Total colonoscopy and capsule endoscopy revealed no polyposis, except in the stomach. The patient was diagnosed with advanced gastric cancer and underwent open total gastrectomy. We speculated that her gastric cancer was a hereditary tumor due to its early onset and accompanying fundic gland polyposis. Germline multi-gene panel testing identified a single-nucleotide variant, c.-191 T > G, in exon 1B of the adenomatous polyposis coli gene, which can cause gastric adenocarcinoma and proximal polyposis of the stomach. To our knowledge, this is the first manuscript to report the variant (c.-191 T > G) in promoter 1B of the adenomatous polyposis coli gene, which is related to a predisposition to gastric adenocarcinoma and proximal polyposis of the stomach.

Complete response induced by nivolumab monotherapy in gastric neuroendocrine carcinoma: a case report.

No standard treatment has been established for gastric neuroendocrine carcinoma (G-NEC). We present the case of a patient with recurrent G-NEC who achieved a complete response (CR) with nivolumab. A woman in her 70 s, with no significant medical or family history of illness, underwent an upper gastrointestinal endoscopy, which revealed a Borrmann type 2 tumor in the gastric antrum. Malignant tumor cells were not detected in the endoscopic biopsy samples; however, a malignant gastric tumor was strongly suspected. Therefore, surgical resection was performed, and the tumor was pathologically diagnosed as a G-NEC with liver metastases. Adjuvant etoposide plus carboplatin was administered for four cycles, but recurrence in the liver was observed 5 months after the completion of adjuvant chemotherapy. Ramucirumab plus paclitaxel and irinotecan were introduced as second and third-line treatments. After these treatments, the mesenteric lymph node metastases expanded. Tumor mutation burden (TMB) was low (five mutations/megabase), and microsatellite instability remained stable. However, programmed death-ligand 1 Combined Positive Score (CPS) was ≥ 5 in the resected sample. Therefore, nivolumab monotherapy was introduced as a fourth-line treatment. The mesenteric lymph node metastases exhibited swelling 3 weeks after the initiation of nivolumab; however, they rapidly shrank, and CR was later achieved. Treatment with nivolumab is currently ongoing for 12 months. This is the first report of nivolumab monotherapy in a patient with G-NEC who showed pseudo-progression. Even in TMB-low and microsatellite stable cases, nivolumab may be a viable option for patients with G-NEC.

Primary omental smooth muscle tumor in an adult male: a diagnostic dilemma for leiomyoma: a case report.

BACKGROUND: The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior omental smooth muscle tumor case in an adult male patient. CASE PRESENTATION: A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up. DISCUSSION AND CONCLUSION: We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.

Mutation profile and programmed death ligand 1 status of patients with non-small cell lung cancer diagnosed with "adenocarcinoma" and "non-small cell carcinoma favor adenocarcinoma".

BACKGROUND: The terminology for lung cancer diagnosis in small biopsies was adopted in the 2015 World Health Organization classification. If non-small cell lung cancer (NSCLC) has no clear adenocarcinoma (AD) or squamous cell carcinoma morphology, the tumor is further classified based on mucin or immunohistochemical staining as NSCLC favor AD (NFAD), NSCLC favor squamous cell carcinoma, or NSCLC not otherwise specified. Since this new term was defined, the difference between AD and NFAD has not yet been fully explored. This study aimed to examine the differences in clinical background, gene alteration frequency, and programmed death ligand 1 (PD-L1) expression. METHODS: We included patients diagnosed with AD or NFAD with small samples, and who underwent testing with the Oncomine Dx target test between August 2019 and April 2023 in Kanagawa Cancer Center. RESULTS: This study comprised 268 patients. A total of 96 patients underwent surgery after AD or NFAD diagnosis. The clinical stage was more advanced and pathological N0 was lower in NFAD than in AD. The pathology of the surgical specimens revealed that solid predominant AD was significantly more common in NFAD than in AD (p < 0.001). In both AD and NFAD, EGFR mutation was the most frequent gene alteration, followed by KRAS mutation. The frequency of EGFR mutations was significantly higher in AD than in NFAD. PD-L1 expression was significantly higher in NFAD than in AD (p < 0.001). CONCLUSION: This study shows a clear difference between AD and NFAD in terms of cancer progression, pathological features of the main tumor, genetic characteristics, and PD-L1 expression.