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Introduction: A recent prospective randomized study demonstrated that minimally invasive surgery (MIS) was inferior to open surgery in disease survival in early-stage cervical cancer. Our aim was to investigate whether there were survival benefits of preoperative conization prior to MIS for early-stage cervical cancer. Methods: We retrospectively analyzed patients who eventually underwent definitive MIS with stage IA2 to IB1 (no >2 cm) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Preoperatively, the patients were separated into 2 groups: one managed with conization and the other undergoing biopsy without conization. Propensity scoring weight and matching were used to reduce the influence of possible allocation biases. The Cox regression model was used for univariate and multivariate analyses of disease recurrence and survival. Results: 227 patients were contained in this study (99 patients in the conization group and 128 patients in the nonconization group). The 5-year DFS of the conization group was statistically better than that of the nonconization group (98.4% vs. 91.8%, p = 0.011). By univariate analysis, conization (HR = 0.11, 95% CI = 0.01–0.87, p = 0.03) and histologic cell type (p = 0.01) were considered as risk factors for recurrence. Multivariate analysis further confirmed conization (HR = 0.04, 95% CI = 0.01–0.51, p = 0.01) and histologic cell type (p < 0.01) correlated with DFS. After propensity score matching (1:1), 84 patients were included in the conization and nonconization groups, respectively, with 5-year DFS still higher in the conization group (98.3% vs. 92.9%, p = 0.037). The results after univariate and multivariate analyses were consistent with those prior to propensity score matching. Conclusion: Preoperative conization in conjunction with MIS seemed to be a safe and feasible approach, with results that may have implications for the reduction of recurrence. Histologic cell type also impacted survival. Therefore, more future prospective studies are warranted.

Lung cancer (LC) is one of the most serious cancers threatening human health. Histopathological examination is the gold standard for qualitative and clinical staging of lung tumors. However, the process for doctors to examine thousands of histopathological images is very cumbersome, especially for doctors with less experience. Therefore, objective pathological diagnosis results can effectively help doctors choose the most appropriate treatment mode, thereby improving the survival rate of patients. For the current problem of incomplete experimental subjects in the computer-aided diagnosis of lung cancer subtypes, this study included relatively rare lung adenosquamous carcinoma (ASC) samples for the first time, and proposed a computer-aided diagnosis method based on histopathological images of ASC, lung squamous cell carcinoma (LUSC) and small cell lung carcinoma (SCLC). Firstly, the multidimensional features of 121 LC histopathological images were extracted, and then the relevant features (Relief) algorithm was used for feature selection. The support vector machines (SVMs) classifier was used to classify LC subtypes, and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to make it more intuitive evaluate the generalization ability of the classifier. Finally, through a horizontal comparison with a variety of mainstream classification models, experiments show that the classification effect achieved by the Relief-SVM model is the best. The LUSC-ASC classification accuracy was 73.91%, the LUSC-SCLC classification accuracy was 83.91% and the ASC-SCLC classification accuracy was 73.67%. Our experimental results verify the potential of the auxiliary diagnosis model constructed by machine learning (ML) in the diagnosis of LC.

A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.

Glassy cell carcinoma of the cervix is a rare subtype of adenosquamous carcinoma associated with aggressive course and poor prognosis. It is considered to originate from the subcylindrical reserve cells of the cervix and has been associated with human papillomavirus. Histologically glassy cell carcinoma is composed of nestes of large cells with ground glass cytoplasm and large vesicular nuclei with prominent nucleoli. Nuclear pleomorphism and tumor giant cells are frequently seen. Mitotic activity is brisk. Infiltration by eosinophils and plasma cells with admixture of lymphocytes is a characteristic feature. Focal squamous and glandular differentiation may be seen. The immunohistochemistry markers are positive for squamous cell carcinoma (p63, CK34) and adenocarcinoma(MUC1, MUC2, CEA).Here we present a case of 49 year old female diagnosed as glassy cell carcinoma histologically and immunohistochemically. Keywords: Cervical cancer, Glassy cell carcinoma.

Adenosquamous proliferation (ASP), characterised by ductal structures with a dual glandular and squamous phenotype within desmoplastic stroma, is essentially a hallmark of various sclerosing lesions of the breast (SL) and breast lesions with sclerosis (BLWS), not including sclerosing adenosis. In radial scar/complex sclerosing lesion (RS/CSL), clonality has been previously demonstrated in microdissected ASP. SL/BLWS encompass a diverse range of pathological entities that historically have an equally diverse list of names, often for histologically alike or identical lesions at different anatomical locations. In common they are comprised of one or more components of fibrocystic or proliferative breast disease and papillomata, which become distorted and even obliterated by a sclerosing process that appears to be associated with and/or secondary to ASP, which in an individual lesion may be inconspicuous at the time of biopsy. The histological overlap of various SL/BLWS with RS/CSL, in which a nidus containing ASP is pathognomonic of early lesions, also supports a common element of ASP across various SL/BLWS. SL/BLWS show an interesting association with low-grade metaplastic carcinoma, particularly low-grade adenosquamous carcinoma (LGASC) with which, they appear to form a histological and possible biological spectrum because ASP and LGASC share similar histological and immunophenotypical characteristics. The presentation of ASP in various SL/BLWS will be discussed.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with non-small cell lung cancer with EGFR mutations. However, acquired resistance to EGFR-TKIs seems inevitable and the mechanism of drug resistance has not been fully defined. There is no effective treatment for patients with advanced lung adenocarcinoma who are resistant to TKIs owing to pathologic type conversion. Case presentation: We report a patient who was initially diagnosed with lung adenocarcinoma. At first, she was sensitive to the first-generation TKI icotinib. After 17 months of treatment, the patient acquired resistance to icotinib. Moreover, after tumor resection, immunohistochemical analysis showed pathologic change from adenocarcinoma to adenosquamous carcinoma, and next-generation sequencing technology discovered EGFR exon19 p.745-750 del, exon20 p.T790M, and KMT2C exon 18 p.R973G mutations. After video-assisted tumor resection, the patient is receiving osimertinib (AZD 9291). Current overall survival is 60 months. Conclusions: Surgical intervention may prolong survival time in patients with acquired TKI resistance, especially when there is no evidence of metastasis.

Adenosquamous carcinoma of the lung (ASC) is a rare subtype of non-small cell lung cancer, consisting of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) components. ASC shows morphological characteristics of classic LUAD and LUSC but behaves more aggressively. Although ASC can serve as a model of lung cancer heterogeneity and transdifferentiation, its genomic background remains poorly understood. In this study, we sought to explore the genomic landscape of macrodissected LUAD and LUSC components of three ASC using whole exome sequencing (WES). Identified truncal mutations included the pan-cancer tumor-suppressor gene TP53 but also EGFR, BRAF, and MET, which are characteristic for LUAD but uncommon in LUSC. No truncal mutation of classical LUSC driver mutations were found. Both components showed unique driver mutations that did not overlap between the three ASC. Mutational signatures of truncal mutations differed from those of the branch mutations in their descendants LUAD and LUSC. Most common signatures were related to aging (1, 5) and smoking (4). Truncal chromosomal copy number aberrations shared by all three ASC included losses of 3p, 15q and 19p, and an amplified region in 5p. Furthermore, we detected loss of STK11 and SOX2 amplification in ASC, which has previously been shown to drive transdifferentiation from LUAD to LUSC in preclinical mouse models. Conclusively, this is the first study using WES to elucidate the clonal evolution of ASC. It provides strong evidence that the LUAD and LUSC components of ASC share a common origin and that the LUAD component appears to transform to LUSC.

Lung adenosquamous carcinomas, cell line H125, with an expression of human epidermal growth factor receptor 1 (HER1), were cultured on two scaffolds of poly(ε-caprolactone) produced through electrospinning, one with a nanometric size and the other with a micrometric size. Cytotoxicity, adhesion and proliferation assays demonstrated the non-cytotoxicity of the scaffolds and the capacity of the cells to grow on them. Tumorlike morphology of cells, HER1 expression and the initial formation of invadopodia were detected through fluorescence microscopy. In the nanometric scaffolds, spheroid formation of cancerous cells was observed. Cells cultured in nanometric scaffolds presented higher resistance to cetuximab than those cultured in micrometric ones and also than cells of two-dimensional cultures. This work demonstrated the potentialities of poly(ε-caprolactone) scaffolds for lung adenosquamous carcinoma cultures and is an initial step for further studies on the growth of cancer cell spheroids on electrospun nanofibers.

Adenocarcinoma and adenosquamous carcinoma (AS) are 2 rare histological types of cervix uteri cancer constituting almost 20% of all cervix cancers, leading to a lack in patient management guidelines. We report the case of a 32-year-old woman with an oligometastatic cervix AS for which a multimodal treatment approach was used. Despite the patient’s bad prognosis, a complete response was achieved, which further resulted in excellent local control and prolonged survival. This case report serves the purpose of encouraging multidisciplinary team work and out-of-the-box thinking that should result in an individualized treatment for rare cancer subtypes.

Metaplastic breast carcinomas constitutes of metaplasia, typically with squamous, spindle, osseous, or chondroid differentiation in the background of adenocarcinoma. We report a case of a 50 year old female who presented with a large, non tender, hard lump since 1 month diagnosed as low grade adenosquamous carcinoma on histopathological examination along with triple negativity on immunohistochemistry. The case is presented to highlight its rarity, histomorphological characteristics, undefined treatment and poor prognosis. Keywords: Metaplastic carcinoma, Breast, Adenosquamous carcinoma.

Objective To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. Methods In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. Results A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40–4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76–5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). Conclusion Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

Pancreatic panniculitis is a rare complication of pancreatic diseases. We aimed to evaluate a case of pancreatic panniculitis. A 58-year-old woman was referred to our hospital with complaints of painful cutaneous nodules on her limbs. Various diagnostic tests confirmed pancreatic panniculitis and pancreatic adenosquamous carcinoma. We diagnosed pancreatic panniculitis by a skin nodule biopsy that revealed fine basophilic material within anucleate cells and neutrophil infiltration. Abdominal imaging detected a tumor with necrosis on the pancreas and endoscopic ultrasound-guided fine-needle aspiration revealed it as an adenocarcinoma. The patient underwent pancreatoduodenectomy after neoadjuvant chemotherapy. The tumor was composed of differentiated adenocarcinoma and squamous cell carcinoma and diagnosed as adenosquamous carcinoma. This is the first report of pancreatic panniculitis in a patient with adenosquamous cell carcinoma of the pancreas.

Context.— While the vast majority of cervical tumors consist of human papillomavirus (HPV)–related squamous cell carcinoma or adenocarcinoma, a subset of rare tumor types, frequently unrelated to HPV, does occur in this location. These tumors vary widely in prognostic and therapeutic implications, and accurate recognition is crucial to providing appropriate treatment. Some are benign or portend a favorable prognosis (adenoid basal carcinoma, ectopic prostate tissue), while others are frankly malignant lesions with a less favorable prognosis (adenoid cystic carcinoma, HPV-negative endocervical adenocarcinoma, mesonephric adenocarcinoma, clear cell carcinoma, small cell carcinoma, and adenosquamous carcinoma). Objective.— To review the morphologic features of uncommon cervical lesions, the utility of immunohistochemistry for distinction between these entities, and the clinical and prognostic implications of accurate diagnosis. Data Sources.— University of Michigan cases and review of the pertinent literature regarding the entities described. Conclusions.— Key morphologic and immunohistochemical features detailed herein will allow for the accurate distinction between these uncommon cervical lesions. Morphology is most useful in discriminating between the entities, as there is frequent immunohistochemical overlap between them; however, in rare instances immunohistochemistry can be useful in resolving the diagnosis.

Aim This study aimed to identify the postoperative histological features affecting the prognosis of patients with early-stage cervical cancer who underwent open radical hysterectomy. Methods This retrospective study enrolled 374 patients with pT1a, 1b1 and 2a1 early-stage cervical cancer who underwent open radical hysterectomy between 2001 and 2018. Survival outcomes were analyzed by Kaplan-Meier method and compared with log-rank test. Using the Cox proportional hazards regression test, we conducted a multivariate analysis for disease-free survival and overall survival. Results Others histology, including other epithelial tumors and neuroendocrine tumors, had a significantly worse prognosis in both disease-free survival and overall survival than those of squamous cell carcinoma and adenocarcinoma (hazard ratio, 4.37 and 11.76; P = 0.006 and P = 0.002, respectively), along with lymph node metastasis (hazard ratio, 2.99 and 7.03; P = 0.009 and P = 0.001, respectively). Conclusion Others histology including adenosquamous carcinoma had a poor prognosis in early-stage cervical cancer as with high-risk factors.

Breast malignancy is the second most common cause of cancer death in women. However, less common breast masses can mimic carcinoma and can pose diagnostic challenges. This case-based review describes a spectrum of rare breast neoplastic and non-neoplastic masses ranging from malignant to benign entities. Malignant masses in this review include adenoid cystic carcinoma, spindle cell lipoma, granular cell tumor, angiosarcoma, glomus tumor, adenosquamous carcinoma, and myofibroblastoma. Benign masses include sarcoidosis, diabetic mastopathy, and cat scratch disease. Demographics and, when relevant, clinical presentation are summarized. Breast imaging appearance on mammography and ultrasound are highlighted along with radiology-pathology correlation with the appearance and characteristics of the histopathological specimen of these rare masses.

A 68-year-old woman with a breast mass was referred to our hospital. Imaging studies showed an oval well-defined mass, 1.3 cm in size, in her left lower outer quadrant of the breast. Core needle biopsy with immunohistochemical staining showed atypical spindle cells forming solid nests with necrosis and papillary lesions, leading to the tentative and pre-operative diagnosis of invasive ductal carcinoma. Due to the absence of daughter nodules, extensive ductal spread, and lymphadenopathy on imaging evaluation, the patient underwent breast-conserving surgery and sentinel node biopsy, resulting in negative surgical margins and no lymph node involvement. Post-operative pathological examination showed triple negative atypical cells with squamous differentiation, squamous cell carcinoma (SCC), with cystic parts and a small amount of low-grade adenosquamous cell carcinoma (LGASC), both encompassing the cystic parts in a contiguous fashion. No cases with synchronous SCC and LGASC in the breast have been reported to date. An etiologic correlation between SCC and LGASC should be further evaluated.

Background Pulmonary segmentectomy is an important surgical option for complete resection in patients with poor lung function. However, correctly recognizing the intersegmental plane for accurate segmentectomy is sometimes difficult. We therefore developed a novel method that allows the detection of intersegmental planes using an indocyanine green (ICG) fluorescence imaging device, photodynamic eye (PDE) camera, PDE-neo. Methods As a prospective study, we performed bronchial ICG-guided segmentectomy using PDE-neo. The patients were placed in a lateral position under general anesthesia, and we performed a combined muscle-sparing minithoracotomy with video assistance. The pulmonary artery, pulmonary vein, and segmental bronchi were separated, and ICG mixed with autologous blood was introduced by spraying through the resected segment bronchi to enable visualization of the intersegmental surface with PDE-neo. This study protocol was approved by the Research Ethics Board of Hamamatsu University School of Medicine, Japan. Written informed consent was obtained from all patients. Results Overall, 10 lung malignancy patients, including 8 males and 2 females, participated in this study from March 2011 to October 2013. The median age was 69 years (range, 29-76 years). Pathologic diagnoses were 7 adenocarcinomas, 1 adenosquamous carcinoma, 1 carcinoid tumor, and 1 lung metastasis from the parotid gland cancer. The intersegmental planes of 8 cases could be identified by this method using a PDE-neo, whereas those of 2 cases did not show clear demarcations. The reason was that because of severe emphysema, air flowed from the resected segment to the surrounding segments, obliterating the demarcation between the two segmental planes. There were no recurrent cases and only two deaths due to other diseases were observed; and the 5-year cause-specific survival rate was 100%. Conclusions Intersegmental planes could be more easily identified using ICG fluorescence imaging during segmentectomy. This method is feasible and effective and has a good long-term prognosis.

Entosis is a type of regulated cell death that promotes cancer cell competition. Though several studies have revealed the molecular mechanisms that govern entosis, the clinical and genetic correlates of entosis in human tumors is less well understood. Here we reviewed entotic cell-in-cell (CIC) patterns in a large single institution sequencing cohort (MSK IMPACT clinical sequencing cohort) of more than 1600 human pancreatic ductal adenocarcinoma (PDAC) samples to identify the genetic and clinical correlates of this cellular feature. After case selection, 516 conventional PDACs and 21 ASCs entered this study and ~45,000 HPFs (median 80 HPFs per sample) were reviewed; 549 entotic-CICs were detected through our cohort. We observed that entotic-CIC occurred more frequently in liver metastasis compared with primary in PDAC. Moreover, poorly differentiated adenocarcinoma or adenosquamous carcinoma had more entotic-CIC than well or moderately differentiated adenocarcinoma. With respect to genetic features TP53 mutations, KRAS amplification, and MYC amplification were significantly associated with entosis in PDAC tissues. From a clinical standpoint entotic CICs were independently associated with a poor prognosis by multivariate Cox regression analysis when considering all cases or primary PDACs specifically. These results provide a contextual basis for understanding entosis in PDAC, a highly aggressive cancer for which molecular insights are needed to improve survival.

Background The Laparoscopic Approach to Cervical Cancer (LACC) trial is the first phase III randomised, multicentred trial to compare oncologic outcomes associated with open radical hysterectomy vs minimally invasive surgery (MIS) for treatment of early cervical cancer. Aim To evaluate our surgical experience in patients with early cervical cancer. Methods and materials The Lifehouse Gynaecologic Oncology database was queried based upon the eligibility criteria of the LACC study and included all FIGO 2009 stage (1A1 with lymph vascular space invasion, 1A2, 1B1) cervical cancer women from 2008-2018. Patients were also included in our study if they had abdominal radical trachelectomy (ART), laparoscopic radical hysterectomy (TLRH) and robotic radical trachelectomy (RRT). Results Forty-six women were identified with four exclusions. Thirty-seven women had stage 1B1 disease, 24 had a squamous cell carcinoma, 15 had an adenocarcinoma and three had an adenosquamous carcinoma of the cervix. Of the 42 eligible patients, 32 underwent an open abdominal approach (26 total abdominal radical hysterectomy (TARH), six ART) and ten a MIS approach (nine TLRH and one RRT) with a mean follow-up of 4.8 years. All 42 women had a pelvic lymph node dissection, eight women had nodal metastases and 16 patients received adjuvant chemoradiation. Two of the nine women in the laparoscopic radical hysterectomy group had a recurrence. Both had adenocarcinoma, stage 1B1 disease. There were no recurrences in the TARH group or radical trachelectomy groups. Conclusion Our data, albeit limited in number, have reflected the results of the LACC trial that MIS was associated with a lower disease-free survival than open radical hysterectomy.