A case of intestinal-type sinonasal adenocarcinoma

Intestinal type sinonasal adenocarcinomas are a rare malignancy of the nasal cavity and paranasal sinuses. Its association with lengthy occupational exposure to dust has been well documented, but sporadic cases have been reported. Diagnostic imaging is essential to exclude metastatic disease from the colon and may be supported by immunohistochemical studies of biopsy specimens. Treatment consists of surgery, radiation, or both, but its effect on prognosis is heavily influenced by the stage at which the disease presents.     

Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.     

Urethral adenocarcinoma associated with intestinal-type metaplasia,case report and literature review

The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in association with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria. Successive biopsies showed glandular epithelium with focal atypia in close association with inflammation, but no overt malignancy. Only on surgical resection was the associated high grade adenocarcinoma revealed. When intestinal-type mucosa is present within a urinary tract biopsy, associated malignancy may be present only focally. Thorough sampling and consideration of the differential diagnosis is imperative.     

Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases.

Nephrogenic metaplasia of the bladder and urethra has been the subject of extensive studies in recent years. However, information about ureteral involvement is still limited because of the rarity of the lesion. We described four cases of nephrogenic metaplasia of the ureter. They occurred in two men and two women whose ages ranged from 46 to 69 years. Three patients had stones, and one had multiple episodes of cystitis and chronic pyelonephritis. The lesions led to ureteral obstruction that in two patients was radiographically suspicious for carcinoma. Microscopically, three lesions were composed of tiny mucin-containing microcysts and medium-sized tubular structures lined by cuboidal cells that showed cytologic atypia characterized by enlarged vesicular nuclei and prominent nucleoli. However, there were no mitotic figures. Two lesions invaded the full thickness of the wall of the ureter and exhibited an infiltrative growth pattern highlighted by cytokeratin stains. The remaining two lesions were confined to the lamina propria. The cells of nephrogenic metaplasia were immunoreactive to cytokeratin 7 and AE1-AE3. They lacked reactivity for monoclonal and polyclonal CEA and p53. The MIB-1-labeling index was <5%. The cytologic atypia and infiltrative growth pattern of ureteral nephrogenic metaplasia should not be misinterpreted as evidence of malignancy. All four patients are alive and symptom free 8 months to 7 years after diagnosis.     

Expression of mismatch repair proteins, beta catenin, and E cadherin in intestinal-type sinonasal adenocarcinoma

BACKGROUND: Despite their histological resemblance to colorectal adenocarcinomas, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). AIMS: To evaluate the possible role of DNA mismatch repair (MMR) gene defects or disruptions of the E cadherin-beta catenin complex in ITAC by investigating the immunohistochemical expression of the MMR gene products, beta catenin, and E cadherin in a group of sporadic ITACs. METHODS: Ten sporadic cases of ITAC were stained with antibodies against MLH1, MSH2, MSH3, MSH6, beta catenin, and E cadherin. RESULTS: Nine cases showed strong nuclear expression of MLH1, whereas one case showed moderate staining. All 10 cases were strongly positive for MSH2 and MSH3. MSH6 was strong in nine cases, and moderate in one. Membranous beta catenin expression was strong in all 10 cases, and no case showed cytoplasmic or nuclear staining. E cadherin was strong in seven cases, and moderate in three cases. CONCLUSIONS: The preserved nuclear expression of MLH1, MSH2, MSH3, and MSH6 suggests that mutations or promoter methylation of MMR genes do not play a role in the pathogenesis of ITAC. The strong membranous staining for E cadherin and beta catenin and lack of abnormal cytoplasmic or nuclear expression is in keeping with the preservation of E cadherin-beta catenin complexes and beta catenin pathways.     

Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal-type adenocarcinoma. A tissue microarray analysis of 62 cases

Franchi A, Palomba A, Fondi C, Miligi L, Paglierani M, Pepi M & Santucci M
(2011) Histopathology 59 , 98–105 Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal‐type adenocarcinoma. A tissue microarray analysis of 62 cases Aims: Sinonasal intestinal‐type adenocarcinoma (ITAC) is an uncommon neoplasm morphologically similar to colorectal adenocarcinoma, with a well‐recognized association with occupational exposure to wood or leather dusts. Here, we analyse several gene products with pivotal roles in tumorigenesis, including p53, p16, deleted in colon cancer (DCC), retinoblastoma, adenomatous polyposis coli, β‐catenin, E‐cadherin and CD10, and discuss their relation to clinical behaviour and to similar pathways in colorectal adenocarcinomas. Methods and results: Immunohistochemical analysis of 62 ITACs was conducted on a tissue microarray. Aberrant expression of p53 and p16 were the most commonly observed alterations (61.3% and 64.5% of cases, respectively). Analysis according to the histological subtype showed that p53 overexpression was less frequent in mucinous ITACs (35.3% versus 71.1%, P = 0.018), while loss of DCC and E‐cadherin were observed more frequently in this subtype (76.5% versus 31.1%, P = 0.002 and 82.4% versus 31.1%, P < 0.001, respectively). No correlation was found between the aberrant expression of these and clinical behaviour while mucinous adenocarcinomas had a significantly worse prognosis, with shorter disease‐free interval and overall survival (P = 0.005 and P < 0.001, respectively). Conclusions: Mucinous ITACs appear to follow a distinct molecular pathway(s) from the non‐mucinous variants, and pursue an aggressive clinical behaviour.     

Expression pattern of CK7, CK20, CDX-2, and villin in intestinal-type sinonasal adenocarcinoma

BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is an uncommon neoplasm, which resembles adenocarcinoma of the gastrointestinal tract. ITAC occurs sporadically or in association with occupational exposure to hardwood dust and other agents. AIMS: To investigate the phenotype and possible pathogenetic mechanisms of primary sinonasal and nasopharyngeal adenocarcinomas by staining for cytokeratin 7 (CK7), CK20, CDX-2, and villin. METHODS: Twelve sporadic sinonasal and nasopharyngeal adenocarcinomas were stained with monoclonal antibodies to CK7, CK20, CDX-2, and villin. The ITACs were classified as papillary, colonic, solid, mixed, or mucinous types. RESULTS: The diagnosis of ITAC was confirmed in 10 cases: five were colonic type and five were papillary. One was a sinonasal papillary low grade adenocarcinoma, and one a papillary nasopharyngeal adenocarcinoma, and these tumours were CK7 positive, but CK20, CDX-2, and villin negative. All ITACs were positive for CK20, CDX-2, and villin, and six were CK7 positive. One ITAC had a focus of intestinal metaplasia away from the invasive carcinoma. CONCLUSIONS: Sinonasal ITACs have a distinctive phenotype, with all cases expressing CK20, CDX-2, and villin. Most ITACs also express CK7, although a proportion of tumours are CK7 negative. ITAC seems to be preceded by intestinal metaplasia of the respiratory mucosa, which is accompanied by a switch to an intestinal phenotype. Although ITACs are morphologically similar, differences in cytokeratin expression patterns suggest two distinct types. The expression pattern of CK7, CK20, CDX-2, and villin positive may be useful in separating these tumours from other non-ITAC adenocarcinomas of the sinonasal tract and nasopharynx.     

Transitional mucosa of colon. A morphological, histochemical, and immunohistochemical study

We studied alterations in the transitional mucosa of the colon in 18 cases of primary colonic adenocarcinoma (4 from the cecum; 4, the ascending colon; 5, the descending colon; 2, the sigmoid colon; and 3, the rectum). One patient had 2 separate primary tumors. Formalin-fixed, paraffin-embedded sections were studied in all cases, and tissues fixed in methacarn fixative were available in 9. Sections of tumor and transitional mucosa were compared with those of normal mucosa distant from the tumor. Sections were stained with hematoxylin-eosin, Masson's trichrome, and alcian blue at a pH of 0.9 (sulfomucin) and at a pH of 2.5 (sialomucin and sulfomucin). Immunoperoxidase stains for collagen type IV (basal lamina) were also performed. Transitional mucosa showed morphological alterations, including increase in mucosal thickness and crypt distortion. An increase in lamina propria fibrosis was noted in transitional mucosa in 3 cases. Abnormal mucin content, consisting of a predominance of sialomucin, was noted in transitional mucosa in 12 cases. In one of these, sialomucin was predominant in both transitional and normal mucosa. No alterations in the thickness of the subepithelial collagen table were noted. Collagen type IV staining was effective in demonstrating an increase in lamina propria vascularity in transitional mucosa in 11 specimens.     

Low grade endometrial endometrioid adenocarcinoma: A review and update with emphasis on morphologic variants,mimics, immunohistochemical and molecular features

Endometrioid adenocarcinoma (ECa) may feature a number of morphologic variations that can pose diagnostic challenge. The purpose of this review and update is to examine the spectrum of morphologic variants and mimics of low-grade (FIGO grades 1 and 2) ECa, with a focus on histologic, immunohistochemical, and molecular features that may inform diagnosis and treatment. In addition to ECa of usual type, variants with unique cytologic and/or architectural features presented include the following: 1) ECa with mucinous differentiation of conventional (Müllerian) type; 2) ECa with squamous differentiation; 3) ECa with morular metaplasia; 4) ECa with patterns resembling cervical transformation zone tissue and/or microglandular hyperplasia; 5) ECa with cytoplasmic clearing; 6) ECa with papillation, including villoglandular variant of ECa, ECa with small nonvillous papillae, and ECa with a “low-grade serous”-like component or surface changes mimicking ovarian serous borderline tumor; 7) corded and hyalinized variant of ECa; 8) ECa with spindled epithelial cells; 9) ECa with sex cord-like pattern; and 10) ECa with other unusual cytologic and associated features. For each variant, relevant differential diagnoses and diagnostic strategies are discussed. The most clinically significant distinctions come into play in the differential diagnosis between low-grade ECa and one of its high-grade mimics. In this setting, the most fundamental tool in the pathologist's diagnostic arsenal is recognition of the low-grade cytologic features typical of low-grade ECa. Circumspect evaluation of cytologic features, complemented by an awareness of the morphologic spectrum, an appropriate battery of immunohistochemical stains when needed, and mindfulness of the clinical scenario, should guide the pathologist to the correct histotype in even challenging cases.     

Squamous metaplasia of the prostate. An immunohistochemical study

Immunoperoxidase strains for prostate-specific antigen (PSA), prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA), and cytokeratins (MAK 6 and CK-KES) were performed on 1 case of squamous cell carcinoma of the prostate and on 13 cases of squamous metaplasia of prostatic epithelium in an effort to demonstrate prostatic origin of the neoplastic and metaplastic cells and to differentiate them from primary or metastatic well-differentiated squamous cell carcinoma. The authors found no specific staining of the metaplastic or neoplastic cells for PSA and only focal single cell PAcP positivity in three cases of squamous metaplasia. All cases showed strong staining of surrounding normal glandular epithelium for both antigens. In all but one case, both the metaplastic and glandular epithelium had positive results for MAK 6 and CK-KES. EMA was expressed strongly in ten cases, was weak or variable in two, and had negative results in two cases of squamous metaplasia. In only four cases did the glandular epithelium have positive results for EMA. The remaining cases showed no staining. PSA and PAcP marking, therefore, may not be useful for separating atypical squamous metaplasia from well-differentiated squamous cell carcinoma or even primary prostatic from metastatic squamous cell carcinoma. These findings suggest that although prostatic glandular epithelial cells retain their ability to express some prostate-associated antigens, this ability is greatly reduced, lost, or not developed in cells that undergo metaplasia into squamous cells or that develop into squamous cell carcinoma.     

Clinical relevance of the histological classification of sinonasal intestinal-type adenocarcinomas.

To verify the prognostic value of the histological typing of intestinal-type adenocarcinoma (ITAC) of the sinonasal tract, 41 such lesions were separately classified by 2 pathologists both according to the World Health Organization (WHO) criteria for the histological typing of large intestine adenocarcinomas (well, moderately, poorly differentiated adenocarcinomas, and mucinous adenocarcinomas) and to the criteria of Kleinsasser and Schroeder (papillary-tubular cylinder cell type, alveolar-goblet cell type, signet-ring cell type, and transitional type). Using the WHO classification, 7 adenocarcinomas (17.1%) were well differentiated, 15 (36.6%) were moderately differentiated, and 6 (14.6%) were poorly differentiated; 13 cases (31.7%) were classified as mucinous adenocarcinoma. Following the Kleinsasser and Schroeder classification, 28 adenocarcinomas were of the papillary-tubular cylinder cell type (PTCC), 6 tumors (14.6%) were of the alveolar-goblet cell type (AGC), 1 (2.4%) was of the signet-ring cell (SRC) type, and 6 (14.6%) were of the transitional (TR) type. The interrater agreement in subtyping for both histological classifications was 92.6% (kappa, 0.89; P < .001). Kaplan-Meier analysis of cases stratified according to WHO classification showed that patients with mucinous and poorly differentiated adenocarcinomas had a significantly shorter disease-free interval and survival rate than patients with well and moderately differentiated adenocarcinomas (P = .02 and P < .001, respectively; log-rank test). Separate evaluation of survival for patients with AGC and TR adenocarcinomas did not show any statistically significant difference (P = .5). Clinical stage was advanced in most cases (92.6% of patients had T3 or T4 carcinomas) and had no prognostic relevance in the current series, as did treatment and occupational exposure. We conclude that the histological typing of ITACs is highly reproducible and appears to be related to the clinical outcome of the tumors. Adenocarcinomas with a prominent (>50%) mucinous component tend to have a similar clinical behavior, irrespective of their cyto-architectural features and the presence of an associated tubulopapillary component. Therefore, the separation into alveolar-goblet, signet-ring, and transitional forms has no prognostic impact.     

Carcinoid tumors arising from Meckel's diverticulum. A clinical, morphologic, and immunohistochemical study

Carcinoid tumors arising from Meckel's diverticulum are rare. They resemble appendiceal carcinoids to the extent that they are usually small, single, and asymptomatic. However, they have generally been likened to jejunoileal carcinoids because of their considerable metastatic potential. Because of the paucity of documented cases, Meckelian carcinoids, unlike their counterparts in other topographic regions of the gastrointestinal tract, have hitherto not been systematically investigated with the use of immunohistochemical techniques. In this study, the immunophenotype of four Meckelian carcinoids was determined and comparatively evaluated against that of the corresponding mucosal epithelial endocrine cells. The results show that the immunohistochemical profile of Meckelian carcinoids is more akin to that of jejunoileal rather than that of appendiceal carcinoids. Despite the lymph node metastasis in one case, there were no complications attributable to any of the carcinoid tumors after a mean follow-up period of 10.2 years; this favorable prognosis is reminiscent of appendiceal carcinoids.     

Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.     

The rarity of rhabdomyosarcomas in the adult. A morphologic and immunohistochemical study

An analysis was made of the rhabdomyosarcomas diagnosed in the Dept. of Pathology of the University of Groningen between 1971 and 1983. Ten cases diagnosed in patients over 30 years of age were studied in detail. After review the diagnosis was discarded on morphologic criteria in all cases. In 9 cases it was changed into malignant fibrous histiocytoma (MFH) and in one case this diagnosis was favoured, but inconclusive. In 5 cases immunohistochemical studies could be performed. In all cases staining for the muscle specific intermediate filaments desmin appeared negative and for the mesenchymal intermediate filaments vimentin positive. These cases were also positive for one or more of the histiocytic markers alpha-1-antichymotrypsin, alpha-1-antitrypsin and lysozyme. It is concluded that rhabdomyosarcoma in older patients is extremely rare and the possible relationship between MFH in the adult and rhabdomyosarcoma in childhood is discussed.