Areas Of Squamous Differentiation Research Articles

Adenocarcinomas of the Gynecologic Tract Involving the Urinary Bladder: A Series of 16 Cases Potentially Mimicking Urothelial Malignancy.

There is limited literature describing gynecologic adenocarcinomas involving the urinary bladder and potential diagnostic pitfalls. To describe key features distinguishing metastatic (or extension of) gynecologic adenocarcinomas from urothelial carcinomas with glandular differentiation. 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. 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. 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.

Sister Mary Joseph Nodule, Umbilical Sentinel for an Endometrioid Endometrial Carcinoma in Postmenopause-Challenges for a Multidisciplinary Approach

A 82 years old, hypertensive, obese, 1 delivery, menopause at 47 yrs, non-smoker, with history of vaginal bleeding in January 2018, is sent by the dermatologist for an irregular umbilical tumor of 2/1 cm, recurrent at 6 weeks post-ablation, microscopically considered as a carcinomatous metastasis. Abdomino-pelvic MRI rises the suspicion of uterine carcinoma, which is confirmed by endometrial biopsy. It is done extrafascial total hysterectomy with bilateral salpingo-oophorectomy, and pelvic lymph dissection and ablation, plus ablation of a skin-adipose-conjunctive peri-and subumbilical area of 5/4 cm. There were no peritoneal metastases, or other viscera abnormalities. The optic microscopy shows moderate differentiated endometrioid endometrial carcinoma, with areas of squamous differentiation, invasion in external myometrial half, without peritoneal invasion, with vessels metastatic embolism, positive pelvic lymph nodes with moderate differentiated endometrioid endometrial carcinoma and desmoplastic reaction; left ovary with mature teratoma. Umbilical specimen has malignant invasion with cribriform and tubular pattern, areas of squamous differentiation, and malignant emboli in vessels. The patient suffered radiotherapy, under oncologic monitoring. The follow up at 6,12,18 and 36 months was with no recurrence in genital, pelvis, peritoneum, abdominal wall. Sister Mary Joseph Nodule (SMJN) has an old history: first observations of assistant catholic nun Mary Joseph Dempsey (Saint Mary’s Hospital, Rochester, Minnesota, USA), William Mayo (1928) description, Hamilton Bailley (1949) characterization. Literature associates SMJN to cancers originating in gastro-intestinal, colonic tract, respiratory, urinary and genital tract: primary ovarian and endometrial cancers; Romanian case is the 36th with endometrial origin. Umbilical invasion may be due to direct vessels’ embolization by malignant endometrial cells, via lymphatics which run along the obliterated umbilical vein, or via the remnant structures of the falciform and umbilical ligaments. Patient is under oncologic monitoring on hormone therapy (Megesin®), with good prognosis up to four years of follow up, different from literature mentioned bad prognosis.

Case report of a pan-cytokeratin negative NUT midline carcinoma of pulmonary origin, a BRD3-NUT variant: Challenges in cytomorphologic presentation.

NUT carcinoma is an aggressive malignancy defined genetically by a balanced translocation of the NUT gene on chromosome 15q14, most commonly associated with the bromodomain-containing protein 4 (BRD4) gene on 19p13.1 but less frequently with variant genes, including BRD3 and NSD-3. We present a case report of a metastatic pulmonary NUT carcinoma found to have a BRD3-NUT fusion and to have only focal pan-cytokeratin staining. Biopsy of the pulmonary mass revealed dyscohesive cells with enlarged nuclei, prominent nucleoli and high nuclear to cytoplasmic ratio without areas of squamous differentiation. Initial immunohistochemical stains were positive for NUT, p63 and retained SMARCA4, while negative for Lu-5 (pan-cytokeratin), TTF-1, p40, S100 protein, OCT-4, HMB-45, SMA, and PAX-8. Tempus ×T assay revealed a BRD3-NUTM1 fusion gene. Post-mortem analysis revealed an ill-defined mass abutting the trachea and superior vena cava, as well as a perirenal mass.

Primary Adenosquamous Carcinoma of Ascending Colon – A Rare Entity

Colorectal cancers (CRC) are on the rise globally with increased incidence rate 5.7/100000 cases in developing countries like India. 1 Majority (90%) of CRC are adenocarcinoma. The primary adenosquamous carcinoma (ASC) of the colon is exceedingly rare variant of adenocarcinoma with incidence of 0.025% and accounts for 0.1% of colonic epithelial malignancies. 2 The squamous differentiation accounts for its aggressiveness and poor prognosis. Here we report a rare case of primary ASC in 80year old male who presented with large bowel obstruction and peritonitis. A 80-year-old male brought to causality with history of fever, vomiting, pain in abdomen, altered sensorium since three days. The clinical examination revealed intestinal obstruction and peritonitis. Patient was immediately subjected for radiological and hematology investigations which showed signs of bowel obstruction and perforation. On emergency exploratory laparotomy, colonic perforation was identified along with an ulcer proliferative mass in ascending colon. Gross examination of right hemicolectomy revealed 9x6x3cm ulcero proliferative mass in ascending colon. The microscopic examination showed an infiltrating tumor composed of adenocarcinoma component and areas of squamous differentiation (60%) noted. Tumor was invading through muscularis propria and serosa. Final diagnosis of primary ASC was made. Colonic ASC is rare and associated with poorer prognosis. The squamous cell differentiation has greater metastatic potential than adenocarcinoma. Compared to adenocarcinoma, ASC is more likely to manifest with advanced disease and complications. Keywords: Adenosquamous, Carcinoma, Colon

Adenosquamous carcinoma in the palate of a dog: case report

Adenosquamous carcinoma is characterized by the simultaneous presence of squamous and glandular components. This article reports a case of adenosquamous carcinoma in the oral mucosa in a dog. Microscopically, the tumour revealed an infiltrative epithelial proliferation with a tubular pattern and areas of squamous differentiation. In the lumina of the tubules, there were eosinophilic material (mucin). The alcian blue staining showed positive intraluminal material and the cytoplasm of neoplastic cells were immunoreactive for cytokeratin, supporting the diagnosis of adenosquamous carcinoma. The cells exhibited reduced or negative immunoreactivity for E-cadherin, which could be associated with more aggressive tumour behaviour and worse prognosis.

Artículo traducido] Perfil de expresión de CD10, BCL-2, p63 y EMA en los carcinomas normales de piel y de células basales: Revaloración inmunohistoquímica

BackgroundBasal cell carcinoma (BCC) is common cutaneous malignancy. AimsTo examine the expression patterns of CD10, p63, BCL-2, and epithelial membrane antigen (EMA) proteins in BCC. Materials and methodsWe used immunohistochemistry to evaluate the expression pattern of these proteins in 45 BCC specimens and their adjacent normal skin. ResultsWe found variations in the expression pattern of these proteins among normal skins and BCC. In normal skins, we found strong EMA cytoplasmic expression (adnexal structures). A strong nuclear p63 protein expression was found in basal and some suprabasal keratinocytes, external root sheath cells of the hair follicles, basal cells of the sebaceous glands, and in sweat glands.CD10 protein expression was seen in peri-adnexal mesenchymal spindle cells and myoepithelial cells of sweat glands.BCL-2 protein expression was confined to the basal cell keratinocytes, epidermal melanocytes, outer root sheath, and infundibulum of the hair follicle. In BCC, we found p63 (diffuse, strong nuclear staining), CD10 (focal, moderate cytoplasmic reactivity), and BCL-2 (focal, moderate cytoplasmic reactivity) protein expression in the neoplastic cells. BCC was consistently negative for EMA (except in areas of squamous differentiation). ConclusionsThere is an altered expression of these proteins in BCC. The underlying molecular mechanisms are open to further investigations.

Expression Profile of CD10, BCL-2, p63, and EMA in the Normal Skin and Basal Cell Carcinomas: An Immunohistochemical Reappraisal

BackgroundBasal cell carcinoma (BCC) is common cutaneous malignancy. AimsTo examine the expression patterns of CD10, p63, BCL-2, and epithelial membrane antigen (EMA) proteins in BCC. Materials and methodsWe used immunohistochemistry to evaluate the expression pattern of these proteins in 45 BCC specimens and their adjacent normal skin. ResultsWe found variations in the expression pattern of these proteins among normal skins and BCC. In normal skins, we found strong EMA cytoplasmic expression (adnexal structures). A strong nuclear p63 protein expression was found in basal and some suprabasal keratinocytes, external root sheath cells of the hair follicles, basal cells of the sebaceous glands, and in sweat glands.CD10 protein expression was seen in peri-adnexal mesenchymal spindle cells and myoepithelial cells of sweat glands.BCL-2 protein expression was confined to the basal cell keratinocytes, epidermal melanocytes, outer root sheath, and infundibulum of the hair follicle. In BCC, we found p63 (diffuse, strong nuclear staining), CD10 (focal, moderate cytoplasmic reactivity), and BCL-2 (focal, moderate cytoplasmic reactivity) protein expression in the neoplastic cells. BCC was consistently negative for EMA (except in areas of squamous differentiation). ConclusionsThere is an altered expression of these proteins in BCC. The underlying molecular mechanisms are open to further investigations.

Utility of p63 and PTEN staining in distinguishing cervical microglandular hyperplasia from endometrial endometrioid carcinoma with microglandular/mucinous features.

AimsDistinction between well‐differentiated endometrial carcinoma (EMCA) with microglandular/mucinous features and benign endocervical microglandular hyperplasia (MGH) can be a diagnostic challenge, especially when tissue is limited. The immunostains used to distinguish endocervical and endometrial carcinoma are less useful when the differential diagnosis is MGH. Here, we investigate the utility of p63 and phosphatase and tensin homologue (PTEN) to aid accurate classification.Methods and resultsCases obtained from our pathology archives included 25 EMCA with mucinous/microglandular features, 26 MGH and nine atypical microglandular proliferations. Cases were assessed for glandular architecture, presence of mucinous and/or eosinophilic luminal secretions, subnuclear vacuoles, foamy histiocytes, inflammation, squamous metaplasia, cytological atypia and mitotic activity. The presence and pattern of immunohistochemical staining for p63 and PTEN was recorded. Microglandular proliferations with cytological atypia, mitotic activity, foamy histiocytes and complex glandular architecture were more commonly seen in EMCA, while small glands, bland nuclei and subnuclear vacuoles were enriched in MGH. All MGH cases displayed p63‐positive subcolumnar reserve cells and retained PTEN expression. Four EMCA cases showed non‐specific focal p63 staining either at the surface of the tumour or in areas of squamous differentiation. p63 and PTEN immunostains accurately predicted the final diagnosis for 3 atypical microglandular proliferation cases with follow‐up.ConclusionsWhile there are morphological characteristics that differentiate EMCA and MGH, there is frequent overlap between these entities. Nonetheless, the pattern and extent of p63 and PTEN can aid accurate classification. Consistent p63‐positive subcolumnar reserve cells were seen only in MGH.

Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma.

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.

INTRA-ORAL SEBACEOUS ADENOMA: A REPORT OF A CASE

Intra-oral sebaceous adenoma (SA) is a rare benign tumor accounting for 0.1% of all salivary gland neoplasms consisting of sebaceous epithelium in a fibrous stroma. A 50-year-old female was referred by her dentist for treatment of an oral lesion in the right buccal mucosa and retromolar trigone. Clinically, a nodule asymptomatic was observed, 1.5 cm, sessile base, rose-colored with the central region yellowish and areas of telangiectasia, with 6 months’ of evolution. The patient also presented Fordyce granules on buccal mucosa, bilaterally. Clinical diagnosis of lipoma was made. After excisional biopsy, the histologic sections revealed a tumor composed of sebaceous cell nests and dilated salivary ducts with areas of squamous differentiation and minimal atypia, enclosed in a fibrous stroma. Minor salivary glands with usual aspects were observed deeply. Final diagnosis was SA, and the patient follow-up is being conducted.

Abstract C41: Establishment of a novel mouse model of pancreatic squamous carcinoma

Abstract Pancreatic cancer is a lethal malignancy with the highest mortality rate among all cancers and a 5-year survival rate of 9% in the US. Among all subtypes of pancreatic cancers, the molecular mechanisms underlying the development of squamous carcinomas are not well understood. While pure squamous carcinoma makes up only 0.05-5% of all pancreatic cancers, it is very aggressive and leads to the worst prognosis among all pancreatic cancers. However, animal models to study the initiation and progression of pancreatic squamous carcinoma are lacking. Genetic studies have recently revealed the molecular signature of pancreatic cancers and identified the transcription factor p63 as a candidate that contributes to the development of pancreatic carcinomas. In one study (Bailey et al., Nature 2016;47-52), upregulation of the p63-mediated transcriptional network was reported. Another genome-wide analysis has identified a SNP in the p63 gene as a risk factor for the development of pancreatic cancers (Childs et al., Nat Genet 2015;911-6). Furthermore, it has been shown that expression of TAp63, an isoform of p63 with a tumor suppressor function, is frequently suppressed in pancreatic cancers (Bailey et al., Nature 2016;47-52). While p63 is rarely mutated in human cancers, ΔNp63α, the predominant isoform of p63 in epithelia, is overexpressed in a variety of human cancers of squamous cell origin. Notably, although p63 proteins are not expressed in normal pancreatic cells, they are expressed at high levels in areas of squamous differentiation of pancreatic cancers (Basturk et al., Modern Pathol 2005;1193-8). We hypothesize that aberrant expression of ΔNp63α in the pancreatic epithelia drives the tumorigenesis of pancreatic squamous carcinomas. To test this hypothesis, we have created transgenic (Tg) mice conditionally expressing ectopic ΔNp63α upon crossing with tissue/cell type-specific Cre-Tg mice in the presence of the K-rasG12D mutation (Hingorani et al., Cancer Cell 2003;437-50), a pancreatic cancer-promoting factor. Our data show that Pdx1Cre:KrasG12D:ΔNp63α-Tg mice develop pancreatic squamous carcinoma as determined by the cellular morphology and the shift of the expression of cytokeratin 8 (K8), a pan-pancreatic epithelial cell marker, into K5, a squamous epithelial cell marker. Interestingly, the absence of the K-ras mutation did not lead to the development of pancreatic tumors, indicating that de novo expression of ΔNp63α alone is not sufficient for the generation of pancreatic squamous carcinomas. None of the mice in our control cohort of the Pdx1Cre:KrasG12D:p53+/- genotype (Bardeesy et al., PNAS 2006;5947-52) developed pancreatic squamous carcinomas or showed p63 expression, emphasizing the functional differences between the two p53 family members. We aim to further characterize our novel animal model and determine the molecular mechanisms by which p63 contributes to the squamous pathogenesis of pancreatic cancer. Citation Format: Filipa Pinto, Tachira Pichardo, Adrien Leu, Makoto Senoo. Establishment of a novel mouse model of pancreatic squamous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C41.

2559 Adenosquamous Carcinoma of the Ileum: A Rare Entity Found Incidentally

INTRODUCTION: Primary small bowel malignancy accounts for 0.6% of all new cancer cases in the U.S. and 1-3% of gastrointestinal tract neoplasms. The common subtypes of malignant small bowel tumors include carcinoid (44%), adenocarcinoma (33%), lymphoma, (15%) and sarcoma (8%). Adenosquamous carcinoma (ASC) is even more rare with only a few cases reported in the literature. The infrequency with which this malignancy is diagnosed and it's late and nonspecific clinical presentation contribute to delayed diagnosis and consequently worse prognosis. CASE DESCRIPTION/METHODS: A 58-year-old African American male presented for a surveillance colonoscopy. His initial screening colonoscopy at 53 years of age showed six polyps, of which, one was a 1 cm sized tubular adenoma. He had no history of gastrointestinal symptoms. During the colonoscopy and routine terminal ileum (TI) intubation, a 4 cm sized mass with central ulceration was visualized. The rest of the colonoscopy was significant only for two small hyperplastic polyps in the rectum. Endoscopic biopsies of the mass showed atypical epithelium. Further, abdominal computed tomography (CT) scan showed no lymphadenopathy or evidence of metastatic disease. He underwent exploratory laparotomy with ileocecectomy and pathology of the mass revealed poorly differentiated, high grade adenocarcinoma with areas of squamous differentiation, arising from a villous adenoma and extending into the muscularis propria (pT2). DISCUSSION: ASC can involve any organ including lungs, pancreas, liver, gallbladder and the gastrointestinal (GI) tract. ASC of ileum is an extremely rare diagnosis. Published case reports show that metastases of small intestinal ASC is common at the time of diagnosis. Our patient was fortuitous enough to have been diagnosed with ileal ASC in an early stage without evidence of metastasis, due to TI intubation during a routine colonoscopy. Surgical resection was likely curative for this patient. To our knowledge, no study has been published to evaluate the prevalence of TI malignant tumors during routine colonoscopy. In addition, intubation of the TI is currently not required during routine colonoscopy. This raises the question if there is utility in measuring TI intubation rates as a potential quality indicator for colonoscopists in the future.

Cytologic Features of Lymphoepithelioma-Like Carcinoma Involving the Parotid: A Case Report

Abstract Fine-needle aspiration biopsies (FNABs) are a common modality used in the evaluation of salivary gland neoplasms. We present the cytologic and histologic features of a rare case of lymphoepithelioma-like carcinoma (LELC) in a 40-year-old Hispanic male with a 1.0-cm painless well-circumscribed parotid mass that had been present for 8 years. FNAB smears showed cohesive groups of intermediate-sized basaloid cells with vesicular nuclei, occasional pleomorphic nuclei and prominent nucleoli, and spindled morphology. Mature lymphocytes were seen in the background, either adjacent to the atypical epithelial cells or dispersed in the background. This lymphoid background raises considerations of salivary gland neoplasms that can have prominent lymphocytic backgrounds, such as acinic cell carcinoma and, more commonly, Warthin’s tumor or metastasis involving intraparotid lymph node. Surgical resection of the parotid showed syncytial sheets of predominantly undifferentiated cells with spindled to epithelioid morphology and occasional prominent nucleoli and focal areas of squamous differentiation. The background showed dense areas of lymphocytes with germinal center formation. Immunohistochemical (IHC) stains showed positive reactivity for p63, p40, and EBV in situ hybridization (EBV ISH) in the tumor cells and negative reactivity for p16. The findings were supportive of LELC if a metastasis from the nasopharynx was excluded. A subsequent nasopharyngeal biopsy was benign. Although histologic features of LELC are well established, we identified rare case reports describing the cytomorphology in the literature. Cytopathologists should be aware of this lesion as another salivary gland neoplasm that can show lymphocytes admixed with the tumor cells and a distinct lymphoid background. The basaloid appearance and cytologic atypia should distinguish it from acinic cell carcinoma and Warthin’s tumor. However, metastatic lesions should also be considered with a distinct lymphoid background and need to be clinically excluded before establishing the diagnosis of LELC.

Low Expression of Toll-like Receptor 4 Is Associated With Poor Prognosis in Bladder Cancer.

The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression. The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis. Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation. Low TLR4 expression was correlated with tumor progression.

Defining the frequency of human papillomavirus and polyomavirus infection in urothelial bladder tumours

Given the contradictory nature of the literature regarding the role of human papillomaviruses and polyomaviruses in the pathogenesis of urothelial bladder cancer (UBC), we sought to investigate the frequency of their involvement in a large cohort of primary UBCs. DNA was extracted from 689 fresh-frozen UBC tissues and screened for the presence of high-risk human papillomavirus (HPV) types 16 and 18 and BKV/JCV genomic DNA by qPCR. In positive cases, viral identity was confirmed by Sanger sequencing and viral gene expression was analysed by RT-PCR or immunohistochemistry. All 689 UBCs were negative for HPV18. One UBC from a female patient with areas of squamous differentiation was positive for HPV16. The qPCR data indicated variable levels of polyomavirus in 49 UBCs. In the UBCs with low Cts we were able to confirm that 23 were BKV and 6 were JCV by Sanger sequencing. Polyomavirus large T antigen expression was low but detectable in 70% of the sequencing-confirmed polyomavirus positive samples. Thus, in United Kingdom patients, the presence of HPV DNA sequences is extremely rare in UBC (<1% of cases). Polyomavirus DNA (predominantly BKV) is more common in UBC, but still only detectable in 7% of cases and in many of these cases at low copy number. We have performed the largest virus screening to date in UBC, finding that HPV16, HPV18 and HPyV are unlikely to be common causative agents in UBC.

Basosquamous Cell Carcinoma of the Lower Lip Arising from Actinic Cheilitis: Case Report and up Date

Background: Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer, considered to be a subtype of basal cell carcinoma (BCC). BSC often produces distant metastases with a higher risk of recurrence than that of BCC which is not commonly found in the lip. Case Report: A 57-year-old white female patient presented an ulcer on her lower lip that had an ongoing development for over six months. Physical examination, photo documentation, videoroscopy, scraped cytology, toluidine blue test, and biopsy of the ulcer were carried out. Results: Upon physical examination we observed an actinic cheilitis associated with the ulcer. Videoroscopy revealed the presence of fissures and erosion that had not been seen by oroscopy. Toluidine blue test was only positive for the region of the ulcer. Cytological analysis revealed rare nests compatible with carcinoma. Histopathology of the biopsy revealed a carcinoma with nests lined by basal cells associated with areas of squamous differentiation. The patient was then referred to surgery for the removal of the BCC. Analysis of the specimen showed free surgical margins and the immunohistochemical panel did not confirm the initial diagnosis of BCC, indicating a subtype of BSC. After surgery, the patient has been followed by periodic consultations. She is well and without further complications. Coments: BSC is considered to be an aggressive and rare tumor affecting mainly upper face and primarily affects men over 60 years of age. Since our patient is a woman presenting the lesion in the lower lip, this highlights the unusual and interesting presentation of this case report.

Syringocystadenocarcinoma Papilliferum With Transition to Areas of Squamous Differentiation

Syringocystadenocarcinoma papilliferum (SCACP) is an exceedingly rare cutaneous adnexal neoplasm, which is typically located in the head and neck, and perianal area. Very few cases have been reported in the literature. Here, we report a case of SCACP with evident transition to squamous differentiation. A 75-year-old white woman presented with 1-year history of a solitary tender nodule in the left upper arm. Physical examination revealed a single, 1.5 × 1.1-cm, erythematous ulcerated nodule within a background of red patch. Biopsy showed an adnexal carcinoma connected to the epidermis and composed of cystic papillary projections admixed with solid basaloid areas with marked cytologic atypia. The basaloid tumor cells appeared to blend with the squamous component that demonstrated ductal formation, which was highlighted by carcinoembryonic antigen. Tumor cells were reactive for both cytokeratins 5/6 and 7. This case represents SCACP arising from syringocystadenoma papilliferum in the upper arm, with distinct transition to areas of squamous differentiation.

Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma

Urothelial carcinoma (UC) with squamous differentiation tends to present at higher stages than pure UC. To distinguish UC with squamous differentiation from pure UC, a sensitive and specific marker is needed. Desmocollin 2 (DSC2) is a protein localized in desmosomal junctions of stratified epithelium, but little is known about its biological significance in bladder cancer. We examined the utility of DSC2 as a diagnostic marker. We analysed the immunohistochemical characteristics of DSC2, and studied the relationship of DSC2 expression with the expression of the known markers uroplakin III (UPIII), cytokeratin (CK)7, CK20, epidermal growth factor receptor (EGFR), and p53. DSC2 staining was detected in 24 of 25 (96%) cases of UC with squamous differentiation, but in none of 85 (0%) cases of pure UC. DSC2 staining was detected only in areas of squamous differentiation. DSC2 expression was mutually exclusive of UPIII expression, and was correlated with EGFR expression. Furthermore, DSC2 expression was correlated with higher stage (P = 0.0314) and poor prognosis (P = 0.0477). DSC2 staining offers high sensitivity (96%) and high specificity (100%) for the detection of squamous differentiation in UC. DSC2 is a useful immunohistochemical marker for separation of UC with squamous differentiation from pure UC.

Bladder Tissue Regeneration with a Collagen-Based Biomatrix in a Model for Bladder Exstrophy Compared to Regeneration in Normal Bladder

Purpose Patients with bladder exstrophy may need a bladder augmentation to improve function. Tissue engineering aims to develop alternatives for the current technique in which intestinal tissue is used. In this study we compared the regeneration of bladder tissue with a collagen-based biomatrix in a sheep model for bladder exstrophy with bladder tissue regeneration in normal bladder. Material and Methods Biomatrices of bovine collagen type I were prepared by subsequent freezing, lyophilisation and crosslinking. In 12 fetal sheep a bladder exstrophy was surgically created at 79 days’ gestation. Lambs were born at full term (140 days' gestation) by normal delivery. After one week the bladder lesion was reconstructed with a collagen biomatrix (group 1). In 10 normal newborn lambs the bladder was opened one week after birth, and closed with a collagen biomatrix (group 2). Functional (cystogram and urodynamic) and histological studies were performed to evaluate the bladders at 1 or 6 months after surgery. Results Survival rate was 58% in group 1 and 90% in group 2. In all animals the cystograms were normal, except for low grade reflux in some lambs of group 1. Urodynamic studies at 6 months showed lower compliance in group 1 (2.0 ± 1.4 versus 4.0 ± 2.7 ml/cmH2O). Histological evaluation at 1 month revealed small areas of squamous differentiation of regenerated urothelium in group 1. At 6 months in both groups normal urothelial lining was present, extracellular matrix was comparable, and slight smooth muscle cell ingrowth was seen. Conclusions This study indicates that bladder regeneration with a collagen-based biomatrix in diseased bladders results in functional bladder tissue with comparable characteristics as normal regenerated bladder tissue. This collagen-based biomatrix might be useful in reconstruction of bladder defects.

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

Changes in reproductive tract histomorphology, and estrogen (ERalpha) and progesterone receptor (PR) expression throughout the breeding cycle were evaluated in free-ranging stranded female California sea lions (Zalophus californianus). Hormone receptor expression in the ovaries, uterus, cervix, and vagina was evaluated using an immunohistochemical technique with monoclonal antibodies. During a large portion of the cycle, ovaries contained both a corpora lutea (CL) and follicles in varying stages of development. In the periods of pupping and estrus during June and July, and in the spring morphologic features of the endometrium suggested estrogen influence. There were areas of squamous differentiation in the pseudostratified columnar epithelium of the cervix and vagina in some animals during estrus and in the spring. Estrogen receptor immunohistochemical scores were highest during pupping and estrus and in the spring and lowest during embryonic diapause. Cyclic changes in uterine PR expression throughout the cycle were minimal. Both ERalpha and PR were expressed in epithelial and stromal cells throughout the cervix and vagina, however, receptor expression was typically higher in the stroma. Stromal cell hormone receptors may play an important role in epithelial responses to circulating sex hormones. The results of this investigation add to the general knowledge of California sea lion reproduction and establish baseline information on reproductive tract hormone receptors that will aid in determining the factors involved in urogenital cancer development in sea lions.