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Background. Lung carcinoma with p40/TTF1 coexpression (LC-PTC) is a very rare tumor with poor prognosis, and few cases have been reported to date. Objectives. To better understand biological behavior and prognosis of LC-PTC. Methods. We collected 9 examples of LC-PTC and compared them with 36 lung adenosquamous carcinomas during the same period in clinicopathologic characteristics, biologic behaviour, and prognosis. Results. Lung carcinoma with p40/TTF1 coexpression mainly occurred in middle-aged and elderly men; 8 tumors belonged to the peripheral type, and 1 belonged to the central type. The rates of lymph node and distant metastasis were 88% (7/8) and 50% (4/8), respectively; 2 patients died during follow-up. Histologically, the LC-PTC showed nest-like growth pattern without glandular growth pattern; the surface of 2 tumors was covered with ciliated columnar epithelium and tumor cells grew under the columnar epithelium. In all patients, tumor cells diffusely coexpressed p40 and TTF1. Although there was no significant difference in the maximum diameter of tumor with lymph node metastasis or with distant metastasis between LC-PTC and lung adenosquamous carcinoma, LC-PTC had a higher rate of lymph node metastasis and distant metastasis. There was no significant difference in overall survival of patients between LC-PTC and lung adenosquamous carcinoma. Additional histologic evaluation of normal pulmonary structures revealed that p40/TTF1 coexpression cells existed in bronchial mucosa and the number of cells coexpressing p40/TTF1 increased gradually from proximal bronchus to distal bronchus. Conclusions. Lung carcinoma with p40/TTF1 coexpression is a rare tumor with high metastatic potential and may originate from p40/TTF1 coexpression cells in distal bronchial mucosa., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Traumatic pulmonary pseudocyst is a rare "cystlike" lung lesion that typically develops following blunt chest trauma. It differs from lung cancer associated with cystic airspaces in terms of pathogenic mechanisms, clinical manifestations, and radiological features. Furthermore, there are few reports of the diagnostic bias between traumatic pulmonary pseudocyst and lung cancer associated with cystic airspaces. Here, we present a rare case of lung cancer associated with cystic airspaces that mimicks traumatic pulmonary pseudocyst., Case Presentation: A 61-year-old man with no chest medical or surgical history, no chest radiologic examination within the last five years, and no smoking history had an air-filled "cystlike" lesion surrounded by solid components and ground-glass opacities in the middle third of the right upper lobe of the lung during a computed tomography evaluation following blunt chest trauma. He was initially diagnosed with traumatic pulmonary pseudocyst and treated conservatively. On the third post-trauma day, he experienced hemoptysis, which was successfully treated with intravenous hemostatic medication. On the ninth post-trauma day, he exhibited a significant hemoptysis and a moderate dyspnea. A subsequent chest computed tomography scan demonstrated that the solid components had entered the lesion's cavity and significantly expanded, and the surrounding ground-glass opacities had slightly enlarged. A contrast-enhanced chest computed tomography scan and a three-dimensional reconstruction computed tomography image confirmed that the solid components were a hematoma caused by damage to the right upper pulmonary vein. A right upper lobectomy was performed based on the concern about severe intrapulmonary bleeding. An intraoperative frozen section analysis showed significant bleeding in the lung parenchyma. Adenosquamous carcinoma was unexpectedly identified during the postoperative pathological examination of the resected specimen. A diagnosis of primary lung adenosquamous carcinoma was made. He was discharged on the seventh postoperative day and followed up for two years without any recurrence., Conclusions: The potential of lung cancer associated with cystic airspaces should be considered for "cystlike" lung lesions discovered in elderly patients after blunt chest trauma. A comprehensive review of the medical history, meticulous analysis of the radiological findings, and close monitoring can help clinicians reduce the risk of diagnostic bias., (© 2024. The Author(s).)

Context.—: There is limited literature describing gynecologic adenocarcinomas involving the urinary bladder and potential diagnostic pitfalls., Objective.—: To describe key features distinguishing metastatic (or extension of) gynecologic adenocarcinomas from urothelial carcinomas with glandular differentiation., Design.—: Retrospective review of surgical pathology cases of gynecologic adenocarcinomas involving the bladder from 2 different institutions, retrieved from surgical pathology archives, was performed. Morphologic features were recorded, along with immunohistochemistry results when available. Electronic medical records were reviewed for clinical and radiographic information., Results.—: Sixteen cases of gynecologic adenocarcinomas (9 endometrial endometrioid adenocarcinomas, 4 endometrial serous carcinomas, 2 high-grade tubo-ovarian serous carcinomas, and 1 cervical adenosquamous carcinoma) involving the bladder were identified. All included cases had mucosal involvement potentially mimicking primary bladder neoplasms, including 4 cases originally diagnosed as urinary carcinomas. Tumors expressed keratin 7 (12 of 13; 92%), PAX8 (11 of 12; 92%), estrogen receptor (11 of 15; 73%), p16 (8 of 11; 73%), progesterone receptor (8 of 14; 57%), GATA3 (5 of 12; 42%), and p63 (3 of 11; 27%); all tumors were negative for keratin 20 (0 of 12). Features supportive of Müllerian origin included prior history of gynecologic malignancy, lack of morphologic heterogeneity in nonendometrioid tumors, and immunophenotypic coexpression of PAX8 and estrogen receptor with absent GATA3. Potential pitfalls seen in a subset of cases included misleading radiologic and cystoscopic findings, replacement of the overlying urothelial mucosa by tumor mimicking precursor lesions, focal GATA3 and/or p63 positivity, and areas of squamous differentiation in tumors of endometrioid histology., Conclusions.—: A combination of clinical history, certain morphologic features, and proper selection of immunohistochemical stains is key for the correct diagnosis of secondary gynecologic adenocarcinomas involving the urinary bladder., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

BACKGROUND Due to several factors such as its specific cellular and biochemical microenvironment, the spleen is not a predestined organ of frequent metastatic colonization in the case of primary solid carcinoma. Hence, the mode of diagnosis and the preferred treatment of a lesion highly suspicious of splenic metastasis must be decided on a case-by-case basis, considering not only the biological tumor entity but also the stage of the primary disease. CASE REPORT In the present case, we demonstrate the clinical course of a 37-year-old female patient who initially presented to our clinic with irregular vaginal bleeding. A consecutive gynecological examination revealed a 3×3-cm large mass of the cervix uteri, and the subsequent histomorphological workup led to the diagnosis of an adenosquamous carcinoma of the cervix uteri. Therapeutically, the patient received multimodal treatment, namely radical hysterectomy with adjuvant radio-chemotherapy. After 1.5 years, the patient presented to our Emergency Department with intermittent left-sided abdominal pain. Subsequent abdominal imaging (computed tomography scan, magnetic resonance imaging, positron emission tomography) determined a metabolically active splenic lesion with a central necrosis - signs of malignancy in line with a splenic metastasis. Presentation and discussion of the case within our interdisciplinary tumor board led to the decision of splenectomy followed by chemotherapy, a procedure that could be considered as therapeutic treatment in such exceptional cases. CONCLUSIONS The collection and reporting of atypical clinical courses remains a key factor in precision medicine to enable the most evidence-based decision making in such cases.

Gastric-type adenocarcinoma is the commonest human papillomavirus (HPV)-independent adenocarcinoma of the cervix. We report a rare case of a primary cervical gastric-type adenocarcinoma with malignant squamous elements (gastric-type adenosquamous carcinoma) in a 64-yr-old female. This is only the third report of a cervical gastric-type adenosquamous carcinoma. The tumor was p16 negative and molecular studies for HPV were negative. Next-generation sequencing showed pathogenic variants in BRCA1 and KRAS , as well as variants of unknown significance in CDK12 and ATM and homozygous deletion of CDKN2A/CDKN2B . Pathologists should be aware that not all cervical adenosquamous carcinomas are HPV-associated and the term gastric-type adenosquamous carcinoma is recommended when malignant squamous elements are present within a gastric-type adenocarcinoma. In reporting this case, we discuss the differential and the possible therapeutic options raised by the presence of pathogenic variants in BRCA1 ., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Aims: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management., Methods and Results: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months., Conclusions: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Although both the 2014 and 2020 World Health Organization (WHO) criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma (ASC), in practice, ASC diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphologic, and clinical features and outcomes associated with ASCs, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed ASCs (including glassy cell carcinoma and related lesions) to confirm an ASC diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as ASCs, 34 retained their ASC diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or ASCs), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy adenocarcinomas were reclassified as poorly differentiated HPV-associated carcinomas based on morphology and immunophenotype. There were no significant immunophenotypic differences between ASCs and pure invasive stratified mucin-producing carcinomas with regard to HPV and other markers including p16 expression. Although limited by a small sample size, survival outcomes seemed to be similar between all groups. ASCs should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The 2 putative glassy cell carcinomas studied did not meet our criteria for ASC and categorizing them as such should be reconsidered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

The adenosquamous carcinoma of the gallbladder is a rare variant accounting for only 1-4% of all primary gallbladder carcinoma. Regardless of the histological types, all gallbladder carcinomas have silent and rapid progression resulting in delayed diagnosis and poor prognosis. Even with medical and/or surgical interventions, the median survival of patients with adenosquamous carcinoma, one of the histological variants, is less than a year. However, we present a case of adenosquamous carcinoma with an unusually better prognosis. A 70-year-old female patient, after being diagnosed with gallbladder carcinoma was suggested for surgical resection but was lost to follow-up since then. Two years later, the patient presented and was managed with extended cholecystectomy. The slow progression and non-recurrence of the tumour during follow-up for two years after the surgery indicates a better prognosis in this case., Keywords: carcinoma; case reports; cholecystectomy; prognosis.

Introduction: Colorectal adenosquamous carcinoma (ASC) represents <0.1% of colorectal cancers. Due to its rarity, there is paucity of data regarding its prognosis and treatment compared to other colorectal cancers. The aim of the study was to evaluate presentation, treatment and prognosis of colorectal ASC in comparison to adenocarcinoma (AC) and squamous cell carcinoma (SCC)., Methods: Adult patients diagnosed with colorectal AC, SCC, and ASC between 2000 and 2017 were identified using Surveillance, Epidemiology, and End Results database., Results: Among the 446,132 patients diagnosed with colorectal cancer, 0.06% had ASC and were more likely to present with higher T stage and distant metastases compared to AC and SCC (p < 0.001). Major surgery was the primary treatment for colonic ASC, while for rectal ASC, chemotherapy and/or radiation were mainly utilized. Localized and distant colonic ASC had an unadjusted 5-year cause-specific survival that was worse than AC, while rectal ASC had the worst survival across all stages., Conclusion: Colorectal ASC usually present with advanced stage and have overall worse prognosis. Standardization of treatment strategies may improve survival in colorectal ASC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The programme death ligand1 and its receptor (PD-1/PD-L1) interaction is a target for blockage by immunotherapy that uses the body's own immune system. Some studies show that PD-L1 expressing tumours are also more aggressive with poor prognosis. This study evaluated the immunohistochemical expression of PD-L1 in uterine cervical carcinomas. Women with cervical cancer would benefit from its use as a marker in therapy and prognosis., Methods: Hospital-based cross-sectional retrospective study was conducted. The study materials included 183 archived formalin fixed and paraffin embedded (FFPE) tissue blocks with histological diagnosis of cervical carcinoma diagnosed in our facility within a five-year period (January 2012 and December 2016) that met the study criteria. Data were extracted from records in the Department and immunohistochemistry was done using polyclonal antibodies to PD-L1 (GTX104763, Genetex). Obtained data were analysed using SPSS version 23. P < 0.05 was considered significant., Results: A hundred and eighty-three cases of cervical cancer were studied. PD-L1 was positive in 57.4% of all cases. The diffuse pattern of staining was the major pattern accounting for 88.5% of positive cases. Poorly differentiated cervical carcinomas are less likely to express PD-L1. Within the histologic types, the squamous cell carcinomas expressed PD-L1 in 58.7%, and 50% of adenocarcinomas were positive. PD-L1 was not expressed in all cases of adenoid cystic carcinomas and basaloid squamous cell carcinomas., Conclusion: A significant population of cervical carcinoma expresses PD-L1 by immunohistochemistry. PD-L1 prevalence is lower amongst the poorly differentiated cancers compared to other grades., Competing Interests: The authors have declared that no competing interests exist.

Colorectal cancer is the third most frequently diagnosed cancer in both men and women. Adenocarcinoma is the most common pathologic subtype of colon cancer and constitutes 86% of all colon cancers. Nontheless, there are other less frequent sybtyes of colorectal carcinomas, such as adenosquamous carcinoma, an extremely rare form of colon cancer, but with worse prognosis and greater potential of metástasis. We present the case of a 68-year-old female presented with a two-month history of anemia, hematochezia and abdominal pain. The colonoscopic study presented a tumor in the ascending colon, which after surgical resection and pathological studies, turned out to be a primary colonoc adenosquamous carcinoma.

Background: To map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV)., Methods: Cervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTV RTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTV K was contoured as proposed by Keenan et al. CTV M was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12-L1 interspace. CTV new was created by modifying CTV RTOG to obtain better coverage., Results: We identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTV RTOG , CTV K , and CTV M covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTV new to cover 96.7% of all PALNs and all nodes in 91.4% of patients., Conclusion: CTV RTOG and CTV K encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered., (© 2021. The Author(s).)

Uterine cervical adenosquamous carcinoma in situ was originally defined as having either a uniform population of cells with features intermediate in appearance between glandular and squamous cells, or a mixture of distinct glandular and squamous components within a single lesion. The former type would likely be reclassified today as stratified mucin-producing intraepithelial lesion, while the latter type is vanishingly rare. Here, we report a novel case of bona fide adenosquamous carcinoma in situ, which exhibits 2 morphologically and immunophenotypically distinct components: (1) an inner glandular component composed of a single layer of p40-negative, ciliated, mucin-producing dysplastic columnar cells and (2) an outer p40-positive, stratified dysplastic squamous component otherwise identical to cervical intraepithelial neoplasia-3. Both components show block-positive staining for p16 and are positive for high-risk human papillomavirus RNA by in situ hybridization. Our finding expands the histological spectrum of human papillomavirus-associated preinvasive cervical lesions while also providing further evidence that human papillomavirus-driven processes can exhibit ciliated morphology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Primary hepatic adenosquamous carcinoma (ASC) is an extremely rare primary hepatic malignant tumor, which is easily misdiagnosed as hepatocellular carcinoma before surgery. It has both the histologic features-adenocarcinoma and squamous cell carcinoma. Primary hepatic ASC incidence rate in intrahepatic cholangiocarcinoma is 2% to 3%. [1] Patients with hepatic ASC may experience recurrence or metastasis after surgery. The epidemiology, clinical diagnosis, etiology, and treatment of the disease remain challenging. It is important to improve the recognition of hepatic ASC because of its bad prognosis. Here, we report a man who had complained of an upper stomachache for 2 months and was diagnosed with primary hepatic ASC by histology and immunohistochemistry (IHC) after laparoscopic hepatectomy. The patient remained asymptomatic and survived well for 2 years post surgery and long-term follow-up was continued till now. In addition, we offer a brief discussion about the histopathological features, clinical behavior, and treatment of hepatic ASC and review the relevant literature., Competing Interests: None

Purpose: We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer., Methods: Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed., Results: Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175)., Conclusion: Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

Objective: The target of this work was to analyze the clinical characteristics and construct nomograms to predict prognosis in patients with cervical adenosquamous carcinoma (ASC). Methods: A total of 788 ASC patients were tracked in the Surveillance, Epidemiology and End Results database. We compared the clinical characteristics and prognostic factors of ASC. Cox regression models were established, and nomograms were constructed and verified. Results: ASC patients have lower age levels and higher histological grades than patients with squamous cell carcinoma. Nomograms were constructed with good consistency and feasibility in clinical practice. The C-indices for overall survival and cancer-specific survival were 0.783 and 0.787, respectively. Conclusion: ASC patients have unique clinicopathological and prognostic characteristics. Nomograms were successfully constructed and verified.

Introduction: The objective of this study was to conduct a retrospective analysis of results of cytology and Roche cobas (RC) and Hybrid Capture 2 (HC2) human papillomavirus (HPV) screening tests in cases of biopsy-proven invasive cervical carcinoma., Materials and Methods: The clinical data were obtained at a university hospital in New York, NY, between 2004 and 2017. Results of cytology, reported per Bethesda classification system, and HPV screening in 177 identified cases with cytology and biopsy-proven diagnosis of cervical carcinoma were included in the analysis., Results: Two cohorts were analyzed. Of the 177 identified cases, cotesting was performed for 100 patients. Among these 100, cotesting screening results would not trigger immediate colposcopy in 6%; HPV screening results were reported as negative in 16% (16% of all RC, 16% of all HC2, 16% total) and, if HPV was the only screening modality, would not trigger a colposcopy. Of the 177 total cases, 128 patients underwent cytology screening prior to biopsy, with a cytology diagnosis that, alone, would not trigger immediate colposcopy in 14%., Conclusions: The HPV DNA screening and cytology screening alone were negative for 16% and 14%, respectively, of patients with biopsy-proven diagnoses of invasive carcinoma of cervical origin, without a significant difference in failure rates between cytology, HC2, and RC. The cotesting approach had a significantly lower failure rate (6%) compared with the 2 other screening modalities alone., (Copyright © 2020. Published by Elsevier Inc.)

Background: Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature., Methods: With institutional review board approval, we identified 23 patients with pancreatic ASC., Results: ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months., Conclusions: ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We compared the clinicopathologic characteristics and prognosis of adenosquamous carcinoma (ASQ) of the breast with invasive ductal carcinoma (IDC), utilizing the National Cancer Database (NCDB) from 2004 to 2015. 1 932 688 female patients had invasive breast carcinoma; 1 421 250 had IDC (73.5%); and 453 had ASQ (0.0002%). When compared to IDC, ASQ patients were significantly (P < .05) older and had grade 1 tumors; negative lymph nodes; ER/PR/HER2-negative tumors; and worse 5-year overall survival (64.9% vs 74%, respectively). Our study, largest to date on ASQ, revealed an aggressive carcinoma with a significantly worse prognosis than IDC. "Personalized medicine" treatment approach for patients with this uncommon carcinoma is needed., (© 2020 Wiley Periodicals LLC.)

Objectives.: With targeted agents, characterizing carcinomas of the gastrointestinal (GI) tract has become more important. We aim to determine the usefulness of p40 in classifying GI tract carcinomas., Methods.: Seventy-five GI carcinomas including 28 squamous cell carcinomas (SCC), 2 adenosquamous carcinomas (ASCA), 21 poorly differentiated carcinomas (PDCA), and 24 adenocarcinomas (AdCA; control group) were stained for p40, p63, and CK5/6. Tumors were scored from 0 to 5 based on extent of staining and marked as positive (score >2) or negative., Results.: p63 was positive in 100% of SCC/ASCA and 12.5% of AdCA. p40 was positive in 92.5% of SCC/ASCA and 4.1% of AdCA. In the PDCA subset, a panel including p63, p40, and MOC31 was the best way to accurately classify most cases., Conclusions.: p63 and CK5/6 are more sensitive but less specific than p40 for SCC/ASCA in GI carcinomas. In PDCA, a panel approach including p63, CK5/6, and p40 may be best in classifying these cases.

Conjunctival adenosquamous carcinoma, also known as mucoepidermoid carcinoma (MEC), is a rare tumor that preferentially affects the perilimbal area of the conjunctiva with aggressive local invasion. Consisting of infiltrative proliferation of squamous cells and mucous cells, its morphologic features are reminiscent of the salivary gland-type MEC except for the absence of intermediate cells and frequent keratin production. We reported 2 cases of conjunctival adenosquamous carcinoma and, for the first time, studied the MAML2 translocation status of this rare entity. The 2 patients were women, aged 45 and 42 years, presenting with an erythematous lesion in the left lower palpebral conjunctiva and a pigmented nodule over the left nasal conjunctiva, respectively. One tumor recurred 6 months after the initial biopsy. Excision with lid reconstruction and postoperative radiotherapy was performed for margin involvement and perineural invasion. This patient was disease free at 3-year follow-up. The other patient was lost to follow-up after tumor excision. Fluorescence in situ hybridization and reverse transcription polymerase chain reaction failed to demonstrate MAML2 translocation and CRCT1-MAML2 transcripts in both tumors. The absence of this characteristic translocation and reappraisal of the cellular composition, morphologic features, and precursor lesion suggest that conjunctival MEC may represent a variant of conjunctival squamous cell carcinoma but not related to the salivary gland-type MEC.

Endobronchial ultrasound has revolutionized the field of bronchoscopy and has become one of the most important tools for the diagnosis of intrathoracic lymphadenopathy and para-bronchial structures. The reach of this technique has not been limited to these structures and pleural lesions have been at times accessible. To our knowledge, pleural fluid collections have not been accessed with endobronchial ultrasound (EBUS) through oesophageal approach and rationale behind using this approach. We report a case of 70 years old man who has been referred from physician for the EBUS in view of hilar mass with mediastinal lymphadenopathy with pleural effusion. The endobronchial ultrasound through oesophagus (EUS-B) was done for thoracocentesis and lymph node cytology evaluation and ultimately endobronchial biopsy of hilar mass was done as rapid on-site (ROSE) analysis of lymph node was suggestive of necrotic tissue. The cytology report of lymph node and pleural effusion was positive for malignant cells. The final diagnosis was metastatic poorly differentiating adeno-squamous carcinoma.

Lung carcinoma is the most common carcinoma seen in males with the skin being a rare metastatic site. Adenosquamous carcinoma as a rare histologic subtype, showing cutaneous metastasis is an unusual event with no reports in the literature till date. Skin metastasis is an alarming sign, carries poor prognosis, and is associated with shortened survival. Herein, we report a case of 60-year-old male who presented with isolated cutaneous metastasis as a chronic nonhealing ulcer over the sternal region for 3 years (unusual) in the first place, without any other associated symptoms and clinical evidence of the primary. Wide local excision of the lesion was performed after proper workup which revealed metastatic adenosquamous carcinoma. The patient was advised systemic chemotherapy. A high index of suspicion along with clinico-radio-pathological correlation in these cases is of utmost importance and forms the basis of accurate diagnosis., Competing Interests: None

Background: According to the proportion of glandular and squamous pathological components, adenosquamous carcinoma (ASC) could be divided into adenocarcinoma (AC) and squamous cell carcinoma (SCC) predominant subtypes. Due to its rarity, no study investigating the impact of different subtypes on the clinical features, radiologic findings and prognosis characteristics of ASC has been reported., Methods: Sixty eight patients who underwent surgical resection for lung adenosquamous carcinoma in our institute between January 2006 and March 2017 were retrospectively reviewed. Data regarding the clinical features, radiologic findings and prognosis characteristics were collected., Results: Thirty nine patients of the study cohort were with AC-predominant ASC and 29 with SCC-predominant ASC. There was no significant difference between the two subgroups in age, gender, smoking history, serum carcinoembryonic antigen (CEA) level and T,N classification. Air bronchogram was found more frequently in AC-predominant ASC than in SCC-predominant ASC (P = 0.046). Multivariate analysis identified pathological subtype (P = 0.022) and CT findings of peripheral location (P = 0.009) to be independent prognostic factors., Conclusions: AC-predominant ASC were more commonly presented with air bronchogram, and were with a better prognosis than SCC-predominant ASC.

A 60-year-old female was admitted to hospital with a continuous fever, a decreased appetite, and abdominal pain. Laboratory tests showed an elevated peripheral leukocyte count (13,800/μl) and increased C-reactive protein (19.1 mg/dl) and carbohydrate antigen 19-9 (4057 U/ml) levels. Abdominal contrast-enhanced computed tomography showed multiple bulky hypovascular nodules in the liver, swelling of the paraaortic lymph nodes, and a hypovascular mass (diameter 3.0 cm) in the pancreatic body. The serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were 172 pg/μl and 541 pg/µl, respectively. Liver biopsy specimens revealed an adenosquamous carcinoma, which was positively immunostained for G-CSF. We diagnosed the patient with G-CSF-producing pancreatic cancer with multiple metastases. Four courses of gemcitabine with dexamethasone and one course of nab-paclitaxel and gemcitabine were administered. Although the pancreatic tumor and paraaortic lymph node metastases decreased in size, the liver metastases continued to grow. The patient died 4 months after the diagnosis of pancreatic cancer. An autopsy resulted in the tumor being diagnosed as poorly differentiated adenosquamous pancreatic carcinoma, which was histopathologically G-CSF-positive. Although G-CSF-producing pancreatic adenosquamous carcinomas are extremely rare, they have been encountered more frequently in recent years. In such cases, chemotherapy combined with dexamethasone might be effective at temporarily improving the patient's condition.

Lung cancer is the most common cancer worldwide and has the highest mortality rate. Carcinomas comprise 95% of all lung malignancies, the vast majority of which are non-small cell lung carcinomas (NSCLC). Increasingly, the diagnosis of lung cancer is established by examination of small tissue specimens obtained by minimally invasive techniques. It is critical to employ these tissues at maximum efficiency in order to render an accurate pathologic diagnosis and to perform theranostic studies, either genomic or by immunohistochemistry, to demonstrate genetic mutations that make patients eligible for molecularly targeted agents. Currently Thyroid Transcription Factor-1 (TTF-1) and Napsin A are the most commonly used immunohistochemical (IHC) stains to identify primary lung adenocarcinoma, and p40 and cytokeratin 5/6 (CK5/6) are used for squamous cell carcinoma. IHC stains for these markers, are performed either individually (IHC brown staining) or in combination as dual immunostains (i.e. TTF-1 + Napsin A and p40 + CK5/6, utilizing brown and red chromogens). Here we present a novel, truly multiplex immunohistochemical approach that combines staining with the above four antibodies on a single tissue section utilizing four different chromogens to accurately diagnose primary lung adenocarcinomas, squamous cell carcinomas, and combined adenosquamous carcinomas of the lung. Each marker is represented by a distinct color that can be read by a pathologist, using standard, bright field microscopy. We evaluated the ability of pathologists to differentiate NSCLCs using the multiplexed assay as compared to standard, single marker per slide diaminobenzidine (DAB)-based IHC. All cases in a cohort of 264 NSCLCs showed concordance of information (including positivity of stain, intensity of stain and coverage) between single IHC stains and the multiplex assay. This new multiplex IHC offers the capability to accurately diagnose and sub-classify primary lung NSCLCs, while conserving precious tissue for additional testing., Competing Interests: Declaration of competing interest E.A.R., L.E.M., and L.J.B. are employees of Ventana Medical Systems, (Ventana) a member of the Roche Group, in Tucson, AZ, USA. Ventana is the tissue diagnostic division of Roche Diagnostics and is a manufacturer of automated immunohistochemical and in situ hybridization assays. Materials for the study were provided by Roche Tissue Diagnostics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors against programmed cell death protein 1/programmed death-ligand 1 (PD-L1) have proven to be remarkably effective in non-small cell lung cancer. PD-L1 represents a predictive biomarker in lung cancer, although its heterogenous expression represents an emerging challenge for accurate biomarker-based patient selection. Lung adenocarcinomas (ADCs) show a high rate of intratumor morphologic heterogeneity that may reflect a heterogenous molecular and immunophenotypic profile. The aim of our study was to analyze the expression of PD-L1 in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas (mADCs) and adenosquamous lung carcinomas (AdSqLCs). As many as 73 mADCs and 6 AdSqLCs were selected. Comprehensive histologic subtyping was performed, and PD-L1 expression was assessed by immunohistochemistry assay using different primary antibodies and automated immunostainers. Overall, PD-L1 expression was observed in 37 of 79 cases (39.2%) (31 mADCs and all AdSqLCs). PD-L1 expression was heterogenous in 22 of 37 PD-L1-positive cases (23.2% mADC and 83% AdSqLC). PD-L1 expression was observed more frequently in ADC with solid pattern. Heterogeneity of PD-L1 expression was significantly related to the presence of micropapillary (P=0.028) and solid (P=0.017) patterns. All PD-L1-positive cases were epidermal growth factor receptor wild-type, 2 cases harbored concomitantly PD-L1 expression and ALK rearrangement. Our data suggest that PD-L1 expression is quite heterogenous in mADCs and AdSqLCs, partly contributing to explaining the discrepant results between biopsy and surgical resections and discordant clinical effectiveness in regard to PD-L1-positive or negative ADC diagnosed on cytology/small biopsy.

Background: Pancreatic adenosquamous carcinoma has a poor prognosis, with limited prospective trial data to guide optimal treatment. The potential impact of drug metabolism on the treatment response of patients with pancreatic adenosquamous carcinoma is largely unknown., Case Presentation: We describe the case of a 51 year old woman with pancreatic adenosquamous carcinoma who, following surgical resection, experienced early disease relapse during adjuvant gemcitabine therapy. Paradoxically, this was followed by an exceptional response to capecitabine therapy lasting 34.6 months. Strong expression of cytidine deaminase was detected within the tumour., Conclusions: This case study demonstrates that early relapse during adjuvant chemotherapy for pancreatic adenosquamous carcinoma may be compatible with a subsequent exceptional response to second line chemotherapy, an important observation given the poor overall prognosis of patients with adenosquamous carcinoma. Cytidine deaminase is predicted to inactivate gemcitabine and, conversely, catalyze capecitabine activation. We discuss strong intra-tumoural expression of cytidine deaminase as a potential mechanism to explain this patient's disparate responses to gemcitabine and capecitabine therapy, and highlight the benefit that may be gained from considering similar determinants of response to chemotherapy in clinical practice.

Background: The accurate identification of the tissue of origin is critical for optimal management of cancer patients particularly those who develop multiple malignancies; however, conventional diagnostic methods at times may fail to provide conclusive diagnosis of the origin of the malignancy. Herein, we describe the use of targeted sequencing in distinguishing the primary and metastatic tumors in a patient with metachronous malignancies in the lung, colon and kidney., Case Presentation: In December 2016, a 55-year-old Chinese male was diagnosed with stage IB lung adenosquamous carcinoma and treated with left lower lobectomy and 4 cycles of platinum-based chemotherapy. After being disease-free for 3.5 months, three colonic polyps were discovered and were diagnosed as invasive adenocarcinoma after polypectomy. Within 5.4 months from the polypectomy, squamous cell renal carcinoma was identified and was managed by radical nephrectomy. Immunohistochemistry results were inconclusive on the origin of the kidney tumor. Hence, the three archived surgical tissue samples were sequenced using a targeted panel with 520 cancer-related genes. Analysis revealed similar mutational signature between the lung and kidney tumors and a distinct mutational profile for the colon tumor, suggesting that the lung and colon malignancies were primary tumors, while the kidney tumor originated from the lung, revealing a diagnosis of metastatic double primary cancer - lung carcinoma with renal cell metastasis and second primary colon carcinoma., Conclusion: Mutational profiling using targeted sequencing is valuable not only for the detection of actionable mutations, but also in the identification of the origin of tumors. This diagnostic approach should be considered in similar scenarios.

Rationale: Post-hysterectomy collision tumors of the vulva has rarely been reported. Though long-term HPV infection may induce vulva tumor, but the relationship between HPV infection and collision vulva tumor is not clear. And there are no clear rules of the post-hysterectomy cancer surveillance for human papilloma virus (HPV) long-term infections. So here we first report a case of post-hysterectomy rare collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland and hope to bring new direction to our future research., Patient Concerns: A 48-year-old woman with long-term HPV infection, 3 years after hysterectomy, gravida 3, para 2, was admitted to our hospital with complaints of a 4-month history of an itching vulva ulceration. An anabrosis was located on the surface of the solid mass of the bartholin gland at the posterior part of the right labium and the right inguinal lymph nodes were palpable. Result of the incisional biopsy of the ulcer area at local hospital was atypical squamous cells couldn't exclude high-grade squamous intraepithelial lesion (ASC-H). Subsequently more authoritative pathological consultation results suggested squamous cell carcinoma of the vulva., Diagnoses: Post-hysterectomy collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland., Interventions: The extensive excision of the vulva, bilateral inguinal lymph nodes dissection, and local skin flap transposition surgeon was done to this patient. The final certificate diagnosis was: vulvar tumor T1bM0N0 composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland; HPV infection; post hysterectomy, and bilateral salpingectomy., Outcomes: The patient recovered well after surgery, and consequently received 6 courses of TC (paclitaxel + carboplatin) chemotherapy, and 9 months and 13 days followed up. So far patient recorded as complete response (CR)., Lessons: Collision vulva tumor occurred post-hysterectomy is extremely rare. It is most likely related to long-term HPV infection, which suggests us should to modify the manner of the post-hysterectomy cancer surveillance for HPV long-term infections. For patients with high-risk HPV infection, even if the cytology results are negative, we may should perform colposcopy and vulva biopsy more positively to prevent the disease from progressing into cancer. And the pathogenesis of relationship between HPV infection and collision vulva tumor is still need further investigation.

Background: CRTC1-MAML2 fusion is often detected in low- or intermediate-grade salivary mucoepidermoid carcinoma (MEC), and it is associated with a favorable clinical course. Primary MEC of the liver is an extremely rare, aggressive tumor, and no study has investigated CRTC1-MAML2 fusion., Case Presentation: A 79-year-old Japanese female presented with an approx. 5-cm hepatic mass lesion. We surgically resected the lesion under the clinical diagnosis of intrahepatic cholangiocarcinoma. The histological and immunohistochemical findings were consistent with high-grade MEC, consisting of squamoid, mucin-producing, and intermediate tumor cells. Our RT-PCR analysis revealed the presence of CRTC1-MAML2 fusion. This fusion gene was further confirmed by direct sequencing. The patient is still alive almost 10 years after the surgery., Conclusion: This is the first case report of primary MEC of the liver with CRTC1-MAML2 fusion, with long survival. The present case has significant implications for the entity of primary MEC of the liver which should be distinguished from adenosquamous carcinoma.

PURPOSE : Circulating tumour DNA (ctDNA) is a promising biomarker for detection of non-invasive epidermal growth factor receptor ( EGFR ) mutations in patients with non-small-cell lung cancer (NSCLC). However, the existing methods have limitations in sensitivity or in availability. The aim was to evaluate the accuracy of capture target sequencing for detecting EGFR mutations in ctDNA. METHODS : A total of 79 patients with NSCLC and available plasma and matched tissue specimens were enrolled. Through capture target sequencing, mutations were searched in over 20 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. To evaluate the accuracy, detection of EGFR mutations in matched tissue samples was performed by target capture sequencing and the amplification refractory mutation system (ARMS). RESULTS:   : EGFR mutations were discovered in 32.9 % (26/79) of the patients with NSCLC, the overall rate of consistency for the 79 paired plasma and tissue samples was 86.1 % (68/79). The sensitivity and specificity of detecting EGFR mutations in the plasma were 72.7 % and 95.7 %. In terms of the EGFR mutations identified by ARMS, the overall consistency was 78.5 % (62/79) in three groups. Of 21 patients with EGFR sensitive mutation defined by next generation sequencing in ctDNA, 20 (95.2%) showed long-term disease control with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment; the median progression-free survival was 10.8 months (95% CI 9.1 to 16.8). CONCLUSIONS: Target capture sequencing of ctDNA can be used for genotyping of EGFR in patients with NSCLC, which may enable a direct recommendation for EGFR TKI on the basis of positive results with plasma DNA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anaplastic lymphoma kinase-positive lung cancer is a form of lung cancer that accounts for approximately 5% of non-small cell lung cancers. Recently, anaplastic lymphoma kinase inhibitors have been used for treatment of anaplastic lymphoma kinase-positive lung cancer, and their high clinical effect has also been demonstrated in cases of advanced stage lung cancer. Alectinib is an anaplastic lymphoma kinase inhibitor that it is recognized as a standard drug for primary therapy because of its superiority to crizotinib., Case Presentation: A 37-year-old Japanese man was admitted to our hospital due to multiple brain metastases. An autopsy report revealed that the cause of death was anaplastic lymphoma kinase-positive lung cancer, exacerbated in a short period despite treatment with alectinib. Necropsy revealed anaplastic lymphoma kinase-positive adenosquamous carcinoma of the lung, suggesting that it was involved in the prognosis of this patient. Based on the autopsy results, we reviewed the pathological tissue from transbronchial lung biopsy at the time of clinical diagnosis. The tissue specimen for clinical diagnosis in this case was a papillary adenocarcinoma. However, when this tissue was immunostained, thyroid transcription factor 1-negative and cytokeratin 5/6-positive parts were recognized. This result indicates that we could diagnose this patient as having had adenosquamous carcinoma of the lung., Conclusion: In cases of anaplastic lymphoma kinase-positive lung cancer poorly responsive to anaplastic lymphoma kinase inhibitors, re-examination of the tissue should be considered because there is a possibility of anaplastic lymphoma kinase-positive adenosquamous carcinoma.

This report describes a case of primary adenosquamous carcinoma of the liver with hepatolithiasis. A 70's man was followed up at a clinic for hepatolithiasis, gallbladder stone, and dilatation of the intrahepatic duct. He visited our hospital for computed tomography(CT)examination. CT showed a 30mm diameter low-density mass in the S2 liver and dilatation of the intrahe- patic duct filled with hepatolithiasis. Blood examination showed elevated levels of tumor markers(CEA 8.0 ng/mL, CA19-9 19,196 U/mL). We diagnosed the tumor as cholangiocellular carcinoma(cT2N1M0, cStage ⅣA)with hepatolithiasis and performed left hepatectomy and lymphadenectomy. In the specimen, a 39×22mm diameter solid tumor was detected and the intrahepatic duct was filled with haptolithiasis. Pathologically, a mixture of adenocarcinoma and squamous cell carcinoma was observed adjacent to the bile duct. Accordingly, a diagnosis of adenosquamous carcinoma was made(pT3N0M0, pStage Ⅲ). Multiple liver metastases were detected 8 months after the operation, and chemotherapy was started. He remains alive 11 months after the operation. We experienced a rare case of adenosquamous carcinoma in the liver with hepatolithiasis.

Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Adenocarcinoma currently accounts for 10-25% of all uterine cervical carcinomas and has a variety of histopathological subtypes. Among them, mucinous carcinoma gastric type is not associated with high-risk human papillomavirus (HPV) infection and a poor prognosis, while villoglandular carcinoma has an association with high-risk HPV infection and a good prognosis. They show relatively characteristic imaging findings which can be suggested by magnetic resonance imaging (MRI), though the former is sometimes difficult to be distinguished from lobular endocervical glandular hyperplasia. Various kinds of other tumors including squamous cell carcinoma should be also differentiated on MRI, while it is currently difficult to distinguish them on MRI, and HPV screening and pathological confirmation are usually necessary for definite diagnosis and further patient management., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Urine samples provide a potential alternative to physician-taken or self-collected cervical samples for cervical screening. Screening by primary hrHPV testing requires additional risk assessment (so-called triage) of hrHPV-positive women. Molecular markers, such as DNA methylation, have proven most valuable for triage when applied to cervical specimens. This study was set out to compare hrHPV and DNA methylation results in paired urine and cervical scrapes, and to evaluate the feasibility of DNA methylation analysis in urine to detect cervical cancer. Urine samples (n = 41; native and sediment) and paired cervical scrapes (n = 38) from cervical cancer patients, and urine from 44 female controls, were tested for hrHPV and 6 methylation markers. Results on native urine and sediment were highly comparable. A strong agreement was found between hrHPV testing on urine and scrapes (kappa = 0.79). Also, methylation levels in urine were moderately to strongly correlated to those detected in scrapes (r = 0.508-0.717). All markers were significantly increased in urine from cervical cancer patients compared to controls and showed a good discriminatory power for cervical cancer (AUC = 0.744-0.887). Our results show a good agreement of urine-based molecular analysis with reference cervical samples, and suggest that urine-based DNA methylation testing may provide a promising strategy for cervical cancer detection.

Adenosquamous carcinoma (ASC) is a rare malignant tumor of the oral and maxillofacial region that displays histologic features of both adenocarcinoma and squamous cell carcinoma. ASC in the midline dorsum of the tongue is exceedingly rare. We report the case of a 48-year-old man who presented with a painless mass in the midline dorsum of the tongue. Although the case was diagnosed as adenocarcinoma by biopsy, a final diagnosis of ASC was established after surgery. Ten months after the patient's initial visit, no recurrence or metastasis has been noted. ASC in the middle dorsum of the tongue is exceedingly rare, and no examples have been reported hitherto., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)