Enteric-type Adenocarcinoma Research Articles

Frequent nuclear β-catenin expression in pulmonary enteric-type adenocarcinoma according to the current World Health Organization criteria.

Based on the current World Health Organization classification criteria, five of 3895 consecutive cases of surgically resected primary lung carcinomas (0.13%) categorized as enteric-type were analyzed. Three cases completely comprised tumor cells that resemble colorectal adenocarcinoma, while the other two cases exhibited features of conventional adenocarcinomas admixed with enteric components. Immunohistochemically, all patients expressed at least three of the five intestinal markers: CDX2, CK20, HNF4α, MUC2, and SATB2. None of the patients expressed TTF-1 and NKX3.1. Three cases showed nuclear accumulation of β-catenin, indicating activation of the Wnt/β-catenin signaling pathway; APC mutations were detected in one of these cases. TP53 mutations were detected in three cases. Mutated EGFR or ALK fusions were not detected. Our study demonstrates that pulmonary enteric-type adenocarcinomas share immunohistochemical features and genetic alterations with colorectal adenocarcinomas, which are characterized by frequent activation of the Wnt/β-catenin signaling pathway and a lack of actionable mutations.

Lung colloidal adenocarcinoma - A case report and review of relevant documentation

According to the histopathological classification of lung tumors of the World Health Organization (WHO) 2015, update 2021, the adenocarcinoma group includes the following subtypes: (1) minimally invasive adenocarcinoma (MIA); (2) Invasive non-mucinous carcinoma (INMA); (3) Invasive mucinous carcinoma (IMA); (4) Colloidal adenocarcinoma (CA); (5) Fetal cancer (FA); (6) Enteric-type adenocarcinoma (EA). In which group colloidal cancer (CA) is said to be very rare, with high malignancy, rapid progression, very difficult to treat. The definitive diagnosis of lung cancer (LC) in general and Adenocarcinoma in particular is still the absolute role of pathology; The problem of subtype LC diagnosis is essential for treatment and prognosis. We present a rare case of CA with a giant mucinous mass in the lower lobe of the right lung, destroying the diaphragm descending to the abdomen, making preoperative diagnosis extremely difficult. The patient underwent surgery to remove the lower lobe of the right lung, and the postoperative specimens were diagnosed with CA; The prognosis after surgery was very conservative. Through the report, we hope that colleagues will have a better diagnostic approach when encountering a similar case.

Primary HPV-Associated Enteric-Type Adenocarcinoma of Vagina: A Case Report.

Primary enteric type adenocarcinomas of the vagina are extremely rare. We present a 63-year-old woman who had a polypoid mass localized to the distal vagina. The lesion was composed of a columnar glandular cell proliferation with focal cribriforming, reminiscent of tubular adenoma. Immunohistochemical stains were notable for expression of enteric markers (CDX2 and KRT20), as well as negativity for Mullerian markers (PAX8, ER, and PR), diffuse expression for p16, and positivity for high-risk HPV mRNA expression. Ultimately, a diagnosis of vaginal primary HPV-associated enteric type adenocarcinoma was rendered for this unusual lesion. To our knowledge, no prior cases of HPV-associated enteric type adenocarcinomas of the vagina have been described before.

Molecular Genetic Features of Primary Nonurachal Enteric-type Adenocarcinoma, Urachal Adenocarcinoma, Mucinous Adenocarcinoma, and Intestinal Metaplasia/Adenoma: Review of the Literature and Next-generation Sequencing Study

The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to be KRAS in 11.3% of cases, followed by TERT promoter mutations in 28.5%. In addition to KRAS and TERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, including TP53, PIK3CA, CTNNB1, APC, FBXW7, IDH2, and RB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows: TP53 (56%); BRCA2, KMT2B (both 33%); NOTCH2, KDR, ARID1B, POLE, PTEN, KRAS (all 28%); in urachal enteric adenocarcinoma they were as follows: TP53 (86%); PTEN, NOTCH (both 43%); in primary mucinous/colloid adenocarcinomas they were as follows: KRAS, GRIN2A, AURKB (all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows: APC, PRKDC (both 60%); ROS1, ATM, KMT2D (all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms include TP53, APC (in the Wnt pathway), and KRAS (in the MAPK pathway) mutations.

Primary enteric-type adenocarcinoma of the prostatic urethra after brachytherapy: A case report and review of the literature

Primary enteric-type adenocarcinoma of the prostatic urethra after brachytherapy: A case report and review of the literature

Abstract 1707: Enteric-type adenocarcinoma in head and neck: Dissecting oncogenic genes alterations through whole transcriptome analysis

Abstract IntroductionAdenocarcinomas of nose/paranasal are uncommon tumors; an important one is that which shows enteric differentiation (ETA). ETA is typically seen in adults, many whom have had occupational exposure (mainly wood and leather). The histogenesis of ETA is uncertain, an origin from transdifferentiation of the respiratory epithelium is a possibility. We previously reported evidence for such transformation in similar tumors at other anatomic locations (Eustachian tube, base of tongue, epiglottis). Due to the rarity of these tumors, their molecular profile is not well known. To investigate the molecular profile and identify potential oncogenic drivers we compared the whole transcriptome of ETA at different anatomic location in head and neck. Materials and Methods10 adenocarcinomas of head and neck formed the material of this study. These samples along with matching normal mucosa were microdisected from FFPE. Pools of RNA were subjected to expression profiling using whole-transcriptome shotgun sequencing. Results 20 tumors were divided as follows: 10 sinonasal and 10 non-sinonasal adenocarcinomas. The sinonasal adenocarcinomas were classified as 8 ETA and 2 seromucinous type (non-ETA, nasal). The 10 non-sinonasal HN adenocarcinomas divided according to histologies and location: 4 ETA (BOT/mobile-2, submandibular-1, ear-1); 3 mucinous adenocarcinoma (buccal-2; 1 ectopic rests neck L2); 1 adenoid cystic carcinoma of BOT; 1 polymorphous adenocarcinoma of buccal; one larynx metastatic colonic adenocarcinoma. Differential gene expression profiles from adenocarcinomas versus normal mucosa were generated and compared to each other. Comparing all tumors versus all normal mucosal tissues, 3029 genes and noncoding transcripts were detected as differentially expressed with fold change >2 and p-values< 0.05 (1625 upregulated and 1404 downregulated genes). These genes and transcripts were annotated and analyzed using IPA program. Further refined analysis of ETA at sinonasal locations showed 622 specific/ non-overlapping genes (325 upregulated and 297 downregulated). The ETA group at other anatomic location segregated with 3344 specific differentially expressed genes, mostly upregulated (1887 versus 1457 downregulated genes). The highest expressed genes and potential drivers were predominantly development- and differentiation-related genes. ConclusionWe assume that ETA are mainly defined by overexpressed developmental homeobox genes, which provide the potential for transformation/ plasticity, along with the differentiation and proliferation behavior of neoplastic cells. The data form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites, and the contribution of different mucosal components to the etiology/ molecular pathology of ETA. Citation Format: Diana Bell, Achim H. Bell, Ehab Y. Hanna. Enteric-type adenocarcinoma in head and neck: Dissecting oncogenic genes alterations through whole transcriptome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1707.

High-grade neuroendocrine carcinoma of the urachus—report of 3 cases

Most urachal malignancies are composed of pure adenocarcinoma with mucin production. Urachal neuroendocrine carcinoma (NEC) is extremely rare, with only a few cases reported in the literature. Here we report 3 cases of urachal NEC, the largest series of this rare disease from a single institution. The patients were young, with a mean age of 27 years (range, 23-34). The urachal tumors showed 2 distinct components: high-grade NEC and enteric-type adenocarcinoma. The urachal NECs were composed of small cell carcinoma (n=2) or large cell NEC (n=1). The subsequent resection specimens showed that all the tumors were at advanced Sheldon stages. All 3 patients developed metastases, which were composed of NEC exclusively. Two patients died from disease in 10 and 31 months, respectively, and the third patient was alive with widespread metastases at 21 months. Our findings suggest that urachal NEC is an aggressive variant with an overwhelming growth advantage over conventional adenocarcinoma. The presence of high-grade NEC in the urachus is associated with poor prognosis.

Histologic characteristics of thymic adenocarcinomas: Clinicopathologic study of a nine-case series and a review of the literature

Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature.Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract.Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features.In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with adenoid cystic carcinoma-like features.

Primary urachal malignancy: case report and literature review

Dear Editor, We present the case of a 38-year-old nulliparous woman who presented with a 3 months history of lower abdominal pain, dysuria and frequency. She denied weight loss, altered bowel habit or PR bleeding. Examination revealed a pelvic mass palpable to the level of the umbilicus. It was firm, non-tender and immobile. Hb was 9.6 g/dl and CA 125 was 18 U/ml. Her liver function tests, urea and electrolytes were within normal limits. Past history included emergency surgery at 3 days of life for Meckels diverticulum, atrial septal defect repair at 7 years of age and an appendectomy at 8 years of age. She had no previous gynae history or family history of breast, ovarian or bowel carcinoma. An abdominal and pelvic CT scan revealed a 9.5 9 7.7 cm midline abdominal mass suspicious for ovarian malignancy (Figs. 1, 2). The mass appeared adherent to the anterior abdominal wall had irregular margins and fat stranding. It indented small bowel loops and possible invasion of the small bowel was suggested. A further multi-cystic lesion was seen in the left adnexa. No pleural effusion or ascites were present. Multiple mesenteric nodes of 1 cm in diameter were present. She was referred to a tertiary gynaecology oncology centre where a laparotomy was performed with a colorectal surgeon present. She was found to have situs inversus of the abdominal organs, an absent right ovary and fallopian tube and normal left ovary and fallopian tube. The tumour was adherent to the anterior abdominal wall and to the bladder posteriorly. A frozen section confirmed metastatic mucinous adenocarcinoma consistent with an ovarian primary. Also present was a healthy appendix although situated in the left iliac fossa. The mass was resected en bloc (Fig. 3) including much of the rectus muscle, the dome of the bladder, two loops of small bowel and a right hemicolectomy was performed. A simple cystic left paraovarian mass was also removed. Histology showed a signet-ring mucinous adenocarcinoma of the urachus (10 cm) extending from the dome of the bladder with full thickness invasion of the small bowel and inflammatory adhesions to large bowel. All bowel, bladder and soft tissue margins were free of tumour. A normal appendix was noted. 31 lymph nodes isolated were free of tumour. The para-ovarian mass showed signet-ring mucinous adenocarcinoma also consistent with metastasis from urachal malignancy. Peritoneal washings were negative. She recovered well postoperatively and was referred to urology for discussion re-adjuvant chemotherapy. The urachus is a midline vestigial remnant located between the dome of the bladder and the umbilicus (Fig. 4). In the foetus the urachus connects the bladder to the allantois. In normal development the allantois is gradually reduced and obliterated with the urachus becoming a fibrous band extending from the anterior bladder dome to the umbilicus. Primary adenocarcinoma of the bladder accounts for less than 1 % of all bladder malignancies, of these 20–39 % are urachal in origin. Urachal adenocarcinoma is more common in men and tends to present in the fifth and sixth decade of life. The common presenting symptoms are haematuria, pain, irritative voiding symptoms and mucosuria. Most urachal malignancies (70 %) are mucin-producing adenocarcinomas, more rarely it is a non-mucin producing adenocarcinoma (15 %). Consistent with other enteric type adenocarcinomas, urachal cancers may express detectable D. Hayes Ryan (&) P. Paramanathan N. Russell J. Coulter South Infirmary Victoria University Hospital, Cork, Ireland e-mail: dee_hayes_ryan@hotmail.com

Primary retroperitoneal mature cystic teratoma with focal enteric type adenocarcinoma in a post-partum woman: report of a case with literature review

Teratomas are characterized by containing tissue from all three germinal cell layers. Occasionally, somatic type malignancies develop within a mature cystic teratoma. We reported here a rare case of enteric type adenocarcinoma, with associated dysplastic epithelial precursor lesion, arising within a mature cystic teratoma in the retroperitoneum of a 30-year-old woman status post vaginal delivery 11 weeks earlier. The mass is 17.5 cm and cystic. A polypoid mass component measuring 4.7×4.2×2.5 cm was located inside the cystic component. Microscopically, the majority of the specimen was a mature cystic teratoma with all three germinal cell layers. The polypoid mass component was an adenocarcinoma with an adjacent dysplastic epithelial precursor lesion. The adenocarcinoma was diffusely positive for CK20 and CDX-2, and focally positive for CD7, indicating enteric differentiation. A brief review of retroperitoneal mature cystic teratomas with associated somatic type malignancy was performed.

Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

Primary enteric-type adenocarcinoma of the urinary bladder is relatively uncommon. We present our experience with 109 pure, non-urachal cases—the largest series to date. This work was undertaken with the aim of describing the immunohistochemical features of adenocarcinoma of the urinary bladder associated with schistosomiasis, illustrating their histologic and immunohistochemical similarities to colorectal carcinomas. Partial or total cystectomy specimens from a cohort of Egyptian and American patients with the diagnosis of primary adenocarcinoma of the urinary bladder (109 cases) were reviewed. Paraffin sections of each tumour were stained using the labelled streptavidin–biotin method using antibodies cytokeratin 20, cytokeratin 7, CDX2, MLH1, and villin. Clinical follow-up was available for at least 36 months. An enteric (colonic) morphology was seen in most tumours; some with signet ring cells or mucinous elements. Five tumours were composed predominantly of signet ring cells and two demonstrated a pure mucinous morphology. In cases where adjacent normal mucosa was present, 23% showed either colonic metaplasia or intestinal-type cystitis glandularis. Furthermore, 24% of enteric-type adenocarcinomas had associated villous or tubulovillous adenomas with or without dysplasia. Cytokeratin 20 was expressed by 90%, cytokeratin 7 by 17%, CDX2 by 100% and villin and MLH1 by 76% and 48% of tumours respectively. The majority of tumours presented with an advanced stage and followed an aggressive clinical course. In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

A Rare Case of Hematuria from Colonic Adenocarcinoma Spreading to the Bladder via the Stented Ureter

Background The direct extension of advanced tumors from adjacent organs to the bladder is not uncommon. Secondary bladder involvement through hematogenous and/or lymphatic metastases and implant of cells by tumors involving higher urinary tract via the ureter are rare. Therefore, the histological resemblance between primary bladder adenocarcinoma and colorectal adenocarcinoma can be a dilemma for pathologists. Methods A 67-year-old female underwent total right hemicolectomy for ascending colon adenocarcinoma. After a 20-month follow-up the lesion was removed (which was histopathologically similar to the previous colon cancer) and the patient underwent ureteral stenting because of a mass in the right internal iliac nodes with homolateral hydronephrosis. Subsequently intermittent gross hematuria urged on performing cystoscopy detecting a non-papillary mass situated above the right ureteral orifice, previously revealed on ultrasonography and CT scan. Results A TURBT was performed. Histopathologically the mass, partially covered by intact urothelium, consisted of tubular and pseudoglandular structures intermixed with solid foci of mucin-producing signet-ring-cells-type adenocarcinoma, very similar to the original colon cancer. The tumor base was healthy. Immunohistochemically stains for cytokeratin 7 (CK7) and cytokeratin 20 (CK20) presented multifocal positivity, suggesting the colorectal origin of the neoplasm. Conclusions In order to optimize the therapeutic options, it is important to distinguish the primary disease of the bladder from other causes of hematuria, and achieve a correct differentiation between primary enteric-type adenocarcinoma of the bladder and secondary colorectal adenocarcinoma involving the bladder, these entities being morphologically indistinguishable. Therefore, in patients with history of colonic adenocarcinoma, the presence of a subsequent bladder tumor should be considered as an eventuality of a secondary disease.

Urachal Carcinoma

Urachal carcinomas occur mostly in the bladder dome, comprising 22% to 35% of vesical adenocarcinomas, and are generally treated by partial cystectomy with en bloc resection of the median umbilical ligament and umbilicus. Detailed pathologic studies with clinical outcome correlation are few. We reviewed histologic material and clinical data from 24 cases selected from a database of 67 dome-based tumors diagnosed and treated at our institution from 1984 to 2005. Follow-up information was available for all 24 patients. The mean age at diagnosis was 52 years (range: 26 to 68 y). Fifteen patients were male and 9 were female. Location was the dome in 23 and dome and anterior wall in 1. Thirteen cases were pure adenocarcinoma, not otherwise specified, 9 were enteric type adenocarcinoma, and 2 were adenocarcinoma with focal components of lymphoepithelioma-like carcinoma and urothelial carcinoma with cytoplasmic clearing. Signet ring cell features were focally seen in 2 cases. Cystitis cystica and cystitis glandularis were seen in 4 and 2 cases, respectively. In all instances but 1, cystitis cystica/glandularis was focal and predominantly in the bladder overlying the urachal neoplasm. Urachal remnants were identified in 15 cases: the urachal epithelium was benign urothelial-type in 6 cases and showed adenomatous changes in 9. The overlying bladder urothelium was colonized by adenocarcinoma in 3 cases. In all 3, urachal remnants were identified and showed transition from benign to adenomatous epithelium. On immunohistochemistry, these tumors were positive for CK20 and variably positive for CK7 and 34BE12. The majority showed a cytoplasmic membranous staining pattern for beta-catenin, although in 1 case, focal nuclear immunoreactivity was identified. The Sheldon pathologic stage was pT1 in 0, pT2 in 2, pT3a in 8, pT3b in 11, pT3c in 1, pT4a in 1, and pT4b in 1 patient. One patient had a positive soft tissue margin. The mean follow-up period was 40 months (range: 0.3 to 157.6 mo). Seven of 24 (29%) cases recurred locally. The incidence of local recurrence was higher in patients who underwent a partial cystectomy alone (37.5%) versus those who had a more radical surgery (27%). Distant metastases occurred in 9 (37.5%) patients, 4 of whom had no prior local recurrence. Seven patients (29%) died of the disease. All cases with locally recurrent and metastatic disease belonged to stage pT3 or higher. Pathologic stage is an important prognostic factor in urachal carcinoma. Surface urothelial involvement by carcinoma and presence of cystitis cystica/glandularis do not necessarily exclude the diagnosis of urachal carcinoma. Immunostains do not unequivocally discriminate a urachal from a colorectal carcinoma, but diffuse positivity for 34BE12 would support, and diffuse nuclear immunoreactivity for beta-catenin would militate against, a diagnosis of urachal carcinoma. Local recurrence may be owing to seeding within the distal urothelial tract, particularly in tumors with a configuration that is polypoid and which open into the bladder cavity. The type of surgery performed may have an effect on local recurrence despite negative margins of resection.

Immunohistochemical Expression of Prostatic Antigens in Adenocarcinoma and Villous Adenoma of the Urinary Bladder

Adenocarcinomas of the bladder are rare, with the diagnosis dependent on exclusion of secondary involvement by direct extension or metastatic spread from other sites. The recent description of an unusual form of urothelial-type mucinous prostatic adenocarcinoma raises a novel differential diagnosis between adenocarcinomas of the prostate and bladder, and investigation into the utility of classic prostatic immunohistochemical antigens in bladder adenocarcinoma is warranted. We identified 37 primary infiltrating adenocarcinomas of the bladder, which included signet ring cell carcinomas (n=11), urachal adenocarcinomas (n=5), and enteric adenocarcinoma (n=21). Also included for comparison were 3 cases, each of bladder villous adenomas and bladder adenocarcinoma in situ. Tissue microarrays were constructed from each case, with each specimen represented by multiple 1.0-mm cores to assess for tumor protein heterogeneity. Immunohistochemistry for prostate-specific antigen (PSA), prostate specific acid phosphatase (PSAP), P501S (prostein), and prostate specific membrane antigen (PSMA) was performed, and moderate to strong immunoreactivity was considered a positive result. Of the 37 adenocarcinomas, all were negative for PSA and PSAP (0/37; 0%). In contrast, a minority of bladder adenocarcinomas was labeled with the prostate antigens P501S and PSMA. P501S showed moderate diffuse cytoplasmic staining in 4/37 cases (11%), including 3 enteric-type adenocarcinomas and 1 mucinous adenocarcinoma. Additionally, 1 case of adenocarcinoma in situ demonstrated diffuse cytoplasmic staining for P501S. The granular perinuclear staining pattern of P501S typically seen in prostatic adenocarcinoma was absent in all cases of bladder adenocarcinoma. PSMA showed diffuse cytoplasmic staining in 4/37 (11%) infiltrating adenocarcinomas (including 1 signet ring carcinoma and 3 enteric-type adenocarcinomas), and in 1 case of adenocarcinoma in situ. Membranous PSMA staining was evident in an additional 3 tumors, 1 urachal mucinous adenocarcinoma, 1 nonurachal mucinous and signet ring cell adenocarcinoma, and 1 nonurachal villous adenoma. In conclusion, although all cases of bladder adenocarcinoma examined were negative for PSA and PSAP, the surprising finding that a subset of invasive and in situ adenocarcinomas of the bladder demonstrated immunoreactivity for P501S and PSMA should warrant caution when using these markers in differentiating prostatic from bladder adenocarcinomas. The lack of granular perinuclear staining for P501S and the absence of membranous PSMA staining both favor a bladder adenocarcinoma, although rare cases of villous adenoma and adenocarcinoma did show PSMA membranous staining indistinguishable from that seen in prostate cancer. Although the novel antigens P501S and PSMA are fairly specific and more sensitive in the differential diagnosis of prostate and urothelial carcinoma, care must be taken when adenocarcinomas of the bladder are considered within this differential diagnosis.

Sporadic Medullary Carcinoma of the Colon: A Clinicopathologic Comparison With Nonhereditary Poorly Differentiated Enteric-Type Adenocarcinoma and Neuroendocrine Colorectal Carcinoma

Sporadic Medullary Carcinoma of the Colon: A Clinicopathologic Comparison With Nonhereditary Poorly Differentiated Enteric-Type Adenocarcinoma and Neuroendocrine Colorectal Carcinoma

The role of immunohistochemistry in the diagnosis of urinary bladder neoplasms

The spectrum of neoplasms involving the urinary bladder is diverse, and, at times, different entities with distinct prognostic and managerial implications may have significant morphologic overlap. The presence of a neoplasm with an unusual morphologic appearance, such as an undifferentiated spindled, or plasmacytoid pattern may necessitate immunohistochemistry to establish the diagnosis. In this review, we discuss a series of distinct diagnostic scenarios, including high-grade undifferentiated carcinoma versus prostatic adenocarcinoma, enteric-type adenocarcinoma versus secondary colorectal adenocarcinoma, spindle cell proliferations, neoplasms with plasmacytoid morphology, endophytic tumors with a nested growth pattern, and flat urothelial lesions with atypia. We also discuss markers supporting urothelial differentiation in the context of a metastatic carcinoma from an unknown primary. The importance of using a morphologically derived differential diagnosis to guide the selection and interpretation of immunohistochemical studies is emphasized, and the varying utility (specificity) of the individual immunohistochemical markers within each setting is addressed.

Sporadic Medullary Carcinoma of the Colon : A Clinicopathologic Comparison With Nonhereditary Poorly Differentiated Enteric-Type Adenocarcinoma and Neuroendocrine Colorectal Carcinoma

We studied 68 sporadic colorectal carcinomas (CRCs) with medullary features (MCRCs) and compared them with 35 poorly differentiated purely “enteric” CRCs (ECRCs) and 15 purely neuroendocrine carcinomas (NECs) of grades II and III, all in patients lacking a family history of CRC. Potential clinicopathologic differences between the study groups were assessed. MCRCs were significantly more common in the ascending colon than were ECRCs, but there was no significant dissimilarity to NECs. ECRCs occurred more often in the rectosigmoid than MCRCs or NECs. MCRCs arose in older patients, and a marked sex difference also was noted. Despite an infiltrative growth pattern, MCRC was less likely than ECRC to manifest with stage III or IV disease, but there was no stage-related difference from NECs. Although the histologic images of MCRCs were evocative of neuroendocrine differentiation, chromogranin positivity and synaptophysin reactivity in that group did not differ meaningfully from that of ECRCs but was dissimilar to the 100% labeling of NECs. p53 immunolabeling was similar in the 3 tumor groups. Follow-up data in the study cases showed that 5-year mortality was 40% (27/68) for MCRC, 59% (19/32) for ECRC, and 93% (14/15) for NEC. Medullary CRC seems to be a distinct clinicopathologic variant of CRC, which does not have a neuroendocrine lineage. The biologic behavior of MCRC was better than that of ECRC or NEC.

Urothelial carcinoma of the urinary bladder with a component of acinar/tubular type differentiation simulating prostatic adenocarcinoma

We report a case of an 83-year-old man with a high-grade carcinoma of the urinary bladder who underwent cystoprostatectomy. The invasive carcinoma showed mixed, morphologically distinct patterns consisting of conventional high-grade urothelial carcinoma, glandular differentiation resembling enteric type adenocarcinoma, and acinar/tubular type differentiation, morphologically similar to Gleason grade 3 prostatic adenocarcinoma. Immunohistochemical studies revealed the acinar/tubular component of the tumor to be negative for prostate-specific antigen and prostatic acid phosphatase, but positive for cytokeratin 7, cytokeratin 20, high molecular weight cytokeratin (34βE12), and thrombomodulin, consistent with origin from the bladder rather than the prostate. Although bladder carcinomas composed of mixed morphologic patterns are not uncommon, to our knowledge, the presence of acinar/tubular type features simulating prostatic adenocarcinoma in such tumors has not been described elsewhere.

Pelvic tumor with differentiation as rectal adenocarcinoma and chorioncarcinoma but with common molecular characteristics

Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature.Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract.Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features.In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with adenoid cystic carcinoma-like features.

Multimodality Management of Urachal Carcinoma: The M. D. Anderson Cancer Center Experience

Enteric type adenocarcinomas arising in the dome of the bladder or along the urachal ligament are uncommon. To improve our understanding of urachal carcinoma and define outcome with current management, we performed a retrospective review of cases seen at the M. D. Anderson Cancer Center. We reviewed the records of 42 patients with urachal carcinoma evaluated at our institution from 1985 to 2001. Specifically, we sought to evaluate the importance of extent of disease, surgical characteristics and systemic therapy on clinical outcome. Of the 42 patients 7 had clinically evident metastases at diagnosis and 35 had resectable disease that was managed initially with surgery. Overall survival from diagnosis for all 42 patients was 46 months with 40% surviving at 5 years. Of the resected cases 16 (46%) remain disease-free (median followup 31 months). Covariates associated with long-term survival were negative surgical margins (p = 0.004) and absence of nodal involvement (p = 0.01). Median survival from recognition of metastatic disease was 24 months in 26 patients in whom metastases ultimately developed. Chemotherapy for metastatic disease produced only 4 significant responses, including 3 of 9 patients treated with 5-fluorouracil and cisplatin containing regimens. Urachal carcinomas are usually locally advanced at presentation with a high risk of distant metastases. However, long-term survival following radical resection occurs in a significant fraction of patients (16 of 35 in our series), supporting an attempt at margin-negative, en bloc resection if at all possible. Chemotherapy appropriate for enteric type adenocarcinoma can induce objective responses but meaningful improvement in survival is not yet demonstrated.