Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

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.

Cervical Gastric-type Adenosquamous Carcinoma: Case Report of a Rare Neoplasm Associated With a BRCA1 Pathogenic Variant.

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 .

Cervical Adenosquamous Carcinoma: Detailed Analysis of Morphology, Immunohistochemical Profile, and Outcome in 59 Cases.

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.

A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix.

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1-2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), "usual-type" adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient's HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern.

Primary adenosquamous carcinoma of the endometrium with glassy cell features. A diagnostic pitfall as a very rare tumour type in the endometrium.

Primary adenosquamous carcinoma of the endometrium with glassy cell features (ASCGCF) is an extremely rare entity and to date, 16 cases of this entity have been reported in the literature. ASC-GCF is an aggressive histological subtype of cervical carcinoma with rapid growth and early metastases; however, very little is known about those originating from the endometrium as they are limited to only a few case reports. Herein, we report a case of primary adenosquamous carcinoma of the endometrium with extensive glassy cell features which posed a major diagnostic challenge by mimicking many entities with its histological diversity.

Clinical and Histological Basis of Adenosquamous Carcinoma of the Pancreas: A 30-year Experience.

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.

A Novel Ciliated, Mucin-producing Variant of HPV-related Cervical Adenosquamous Carcinoma In Situ: A Case Report.

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.

Analysis of clinical characteristics and prognosis with cervical adenosquamous carcinoma: a large population-based study.

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.

Adenosquamous carcinoma of the breast, an uncommon diagnosis with poor prognosis-Lessons learned from a 12-year analysis of the National Cancer Database.

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.

[Adenosquamous carcinoma of the colon: a case report and review of the literature]. / Carcinoma adenoescamoso de colon: reporte de caso y revisión de la literatura.

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.

Adenocarcinomatous-predominant subtype associated with a better prognosis in adenosquamous lung carcinoma.

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.

Early relapse on adjuvant gemcitabine associated with an exceptional response to 2nd line capecitabine chemotherapy in a patient with pancreatic adenosquamous carcinoma with strong intra-tumoural expression of cytidine deaminase: a case report.

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.

Chromogenic immunohistochemical quadruplex provides accurate diagnostic differentiation of non-small cell lung cancer.

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.

A case report on expanding horizon of endobronchial ultrasound through esophagus.

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.

[A Rare Case of Adenosquamous Carcinoma in the Liver with Hepatolithiasis].

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.

SLN biopsy in cervical cancer patients with tumors larger than 2cm and 4cm.

OBJECTIVES: The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients. METHODS: Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma. RESULTS: The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors<2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510). CONCLUSIONS: If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors<2cm, 2-3.9cm, and ≥4cm.

Spontaneous pulmonary adenosquamous carcinoma in a free-living black capuchin monkey (Sapajus nigritus).

Pulmonary neoplasia is rare among wild New World primates. We report the gross, microscopical, and immunohistochemical features of a primary multicentric pulmonary adenosquamous carcinoma in a free-living black capuchin monkey (Sapajus nigritus). Herein, the spectrum of pulmonary neoplasms in non-human primates is widened and briefly reviewed.

Newly Diagnosed Lung Cancer: Which Molecular Tests Are Needed for Optimal Treatment Decision Making?

The management of advanced non-small-cell lung cancer (NSCLC) has changed dramatically over the past few years due to our expanded knowledge of the molecular basis of lung cancer (driver mutations and immune targets) and drugs that affect these pathways, namely targeted agents and checkpoint inhibitors. Consequently, it is important to test patients with newly diagnosed advanced NSCLC for potentially significant molecular abnormalities prior to the initiation of treatment. This requires close coordination between the surgical pathologist, the molecular pathologist, and the medical oncologist to ensure that the biopsy specimen is used judiciously to get all necessary information. In this article, I suggest an approach to the diagnostic evaluation of patients with newly diagnosed advanced NSCLC, in an attempt to identify the best treatment options for each.

Adenosquamous Carcinoma in the Midline Dorsum of the Tongue: A Rare Case Report.

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.