Non-intestinal Adenocarcinoma Research Articles

Immunoexpression of CDX2 in metastatic nonintestinal adenocarcinomas: an immunohistochemical pitfall and its pathological implications

BackgroundCDX2, a homeobox gene is the marker of intestinal differentiation. Its expression may lead to misdiagnosis while evaluating metastasis from unknown primary. In the present narrative, we discuss the clinical, morphological, and immunohistochemical (IHC) findings of metastatic adenocarcinoma of the lymph node that displayed nuclear immunoexpression of CDX2. However, the clinical and radiological picture supported the non-intestinal primary; prostate in one and lung in the other.Case presentationA 68-year-old man presented cervical lymph node enlargement. An epithelial tumor with acinar and cribriform pattern was seen that showed expression of CK, CDX2, and PSA in IHC. The patients complained of nonspecific symptoms related to both the gastrointestinal system and the prostate. Serum PSA was diagnostic (> 500 ng/ml). Similarly, core biopsy from mediastinal lymph node from a 51-year-male was received with possible differential of cancer and tuberculosis. Moderately differentiated adenocarcinoma was observed with the expression of EMA, CK 7, CDX2, and TTF1. The expression of both CDX2 and TTF1 was patchy. When the patient was called and all the details were sought the computed tomography (CT) thorax showed a lower chest wall lesion and multiple metastasis. The case was hence signed off as primary from lung on basis of clinical picture.ConclusionSuch deviants must be reported and recorded. The knowledge of these will make a pathologist cautious and thus avoid misdiagnosis.

A Case of Sinonasal Low-Grade Nonintestinal Adenocarcinoma That Was Difficult to Diagnose Preoperatively

AbstractWe report a case of sinonasal low-grade, nonintestinal adenocarcinoma (LG non-ITAC). The patient, a 56-year-old woman, was referred to our university hospital for a left nasal tumor with nasal obstruction, epistaxis, and nasal discharge. Nasal endoscopy revealed a nasal polypoid tumor with a smooth margin occupying the left nasal cavity. The sinonasal tumor was diagnosed as an exophytic papilloma by histopathology. Sinonasal contrast computed tomography (CT) confirmed homogeneous opacification of the left frontal, maxillary, and ethmoidal sinuses. There was no evidence of a potential bone defect. T2-weighted magnetic resonance imaging (MRI) showed a relatively uniform high signal intensity area in the left maxillary and frontal sinuses. An area of high signal intensity was also found in a part of the left ethmoid sinus. Left transnasal endoscopic ethmoidectomy was performed under general anesthesia. The tumor in the nasal cavity was prone to bleeding. We defined the site of tumor attachment as the suprabullar cell. The anterior ethmoidal artery was exposed, and the tumor was carefully dissected and removed. Based on the findings of these radiological and histological examinations, the sinonasal tumor was diagnosed as a LG non-ITAC. Sinonasal non-ITAC is an adenocarcinoma without the histopathological characteristics of salivary or intestinal-type adenocarcinoma. Non-ITAC is additionally classified into the high-grade and LG types. LG non-ITAC is very uncommon. Thus far, there is only one published report in the literature on the clinical and therapeutic characteristics of LG non-ITAC in Japan. Non-ITAC has a good prognosis, with a low risk of metastasis. Therefore, it is imperative to suspect and distinguish non-ITAC from other sinonasal tumors with similar symptoms preoperatively.

Skull base low-grade non-intestinal adenocarcinoma in a paediatric patient

Background: Non-intestinal adenocarcinomas of the sinonasal tract are uncommon neoplasms in adults, and particularly rare in the paediatric population. Case presentation: A 10-year-old male presented to the Paediatric Otolaryngology clinic with symptoms of recurrent epistaxis, persistent clear nasal discharge, and a left-sided polypoidal swelling causing nasal obstruction. An endoscopic biopsy of the polyp under general anaesthesia found a mass arising from the anterior olfactory cleft, and the histology report described the mass as a low-grade non-intestinal adenocarcinoma. CT and MRI of the sinuses post-biopsy demonstrated no bony structure infiltration. The patient underwent a further endoscopic operation for definitive excision of the nasal mass, and the histology findings confirmed a complete resection of the tumour. Conclusion: This case demonstrates the first case of a primary low-grade non-intestinal adenocarcinoma originating from the olfactory cleft.

Occurrence of Sinonasal Intestinal-Type Adenocarcinoma and Non-Intestinal-Type Adenocarcinoma in Two Countries with Different Patterns of Wood Dust Exposure.

Simple SummaryWood dust exposure is a reported pathogenetic factor for sinonasal intestinal-type adenocarcinoma, particularly in occupational exposure in wood-working industries. This study characterized wood dust exposure and compared the occurrence of sinonasal intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma between France with predominantly deciduous hardwood forests and Finland with mostly coniferous softwood forests. The findings indicated that sinonasal intestinal-type adenocarcinomas occur much more frequently in France than in Finland and are distinctly more common than non-intestinal adenocarcinomas, while in Finland the reverse is true. This is the first systematic comparison of the occurrence of the two tumor types in countries with distinctly different wood usage and wood dust exposure. It is also the first systematic study on differences in wood dust exposure between sinonasal intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma. The results provide important epidemiological information on pathogenetic differences between the two tumor types, highlighting the significance of the source of the wood dust.Sinonasal intestinal-type adenocarcinoma is strongly associated with hardwood dust exposure. Non-intestinal-type adenocarcinoma is a rarer and less well-known subtype considered not to be related with wood dust exposure. We determined the relative numbers of these two tumor types in 56 sinonasal adenocarcinoma patients in France and Finland, relating them with carefully assessed wood dust exposure histories. Diagnostic workup including immunohistochemistry for the intestinal markers CDX2 and CK20 indicated that the proportions of the two tumors differed significantly between France and Finland. In Finnish samples non-intestinal adenocarcinomas were more common than intestinal-type adenocarcinomas (12 non-intestinal vs. nine intestinal), while in the French samples the reverse was true (six non-intestinal vs. 29 intestinal). Such remarkably dissimilar occurrence of these tumors in France and Finland presumably reflects different pathogenetic circumstances in the two countries, and perhaps their different patterns of wood dust exposure. In France the main source of wood dust is from hardwoods. In Finland it is derived from softwoods. This is the first systematic comparison of the occurrence of intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma in two countries with different wood usage. It appears to be the first systematic study on differences in wood dust exposure between intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma.

ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma: a clinicopathological analysis

Objective: To investigate the clinicopathologic features, immunophenotype, molecular genetic changes of ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma (ETV6-RLGSNAC). Methods: Primary sinonasal epithelial malignant tumors were collected from January 2015 to January 2020 in the Department of Pathology, Eye, Ear, Nose and Throat Hospital affiliated to Fudan University. Through morphological observation, immunohistochemical detection and fluorescence in situ hybridization (FISH), ETV6-RLGSNAC was screened out for clinicopathological feature analysis, and relevant literatures were reviewed. Results: There were 550 cases of primary sinonasal epithelial malignant tumors, among which 82 cases were adenocarcinoma. There were 29 cases of low-grade non-intestinal adenocarcinoma, only 3 cases of ETV6-RLGSNAC were screened out. Of the 3 patients, 2 cases were male and 1 case was female, with a mean age of 54 years (range 37-64 years). The main clinical manifestations were nasal stenosis, nasal obstruction and epistaxis. A neoplasm with smooth surfaces was observed under nasal endoscopy. Imaging showed an expansive mass in the sinonasal area. Gross examination showed gray-yellow cut surface with firm texture and a maximum diameter of 2-3 cm. Microscopically, tumors were non-encapsulated and well-circumscribed with expansive growth pattern. The tumor cells were small and mild, cylindrical and cuboidal, and arranged in regular glandular and trabecular patterns. The cytoplasm was eosinophilic and the nuclei were basally located with inconspicuous nucleoli. By immunohistochemistry (IHC), CK7, SOX-10, DOG1 and vimentin were positive and S-100 expressed in small clusters of cells in all cases. GCDFP-15, CD56, CK20, mammaglobin, TTF-1, NR4A3 were all negative. The Ki-67 value-added index of all cases was low (<5%). ETV6 gene rearrangement was confirmed in all the cases by FISH, and two cases had NTRK3 gene rearrangement. All three patients underwent radical resection after diagnosis, and one also had adjuvant radiotherapy. All three patients were available with a follow-up time of 12-25 months, and all were recurrence free. Conclusions: ETV6-RLGSNAC is a rare low-grade and newly named non-intestinal adenocarcinoma. The histomorphology is similar to other low-grade nasal sinonasal adenocarcinomas and some salivary gland tumors. IHC and FISH are useful for the diagnosis and differential diagnosis.

High-grade non-salivary non-intestinal adenocarcinoma of the nasal cavity-a less known entity

&lt;p&gt;Sinonasal region, with its anatomical complexity, is commonly associated with a number of tumors. Salivary gland tumors are frequent but adenocarcinomas are uncommon.Here presented an uncommon case of high-grade adenocarcinoma non-salivary non-intestinal type.&lt;/p&gt;

Non-salivary and non-intestinal orbital adenocarcinoma

&lt;p&gt;The non-salivary and non-intestinal adenocarcinomas are glandular tumors that include cases of low grade with low metastatic potential and high-grade ones, with aggressive metastatic potential. We present a clinical case of a 47 years old patient, referred to an ENT specialist because of swelling of the inner corner of right eye. Computed tomography (CT) and magnetic resonance imaging showed a proliferation process. The histopathological examination of the tumor biopsy revealed a high grade, non-salivary and non-intestinal orbital adenocarcinoma. Afterwards we review the literature on the subject. The primary non-salivary and non-intestinal orbital adenocarcinoma is characterized by locoregional aggressiveness, making treatment difficult and often mutilating. The prognosis is generally unfavourable. The clinician must exclude a malignant process of lacrimal sac in any patient presenting with a mass of the inner corner of the eye, with the help of the CT associated with magnetic resonance imaging. At the slightest doubt, the biopsy must be obtained. The treatment is multidisciplinary.&lt;/p&gt;

Low-Grade Epithelial Proliferations of the Sinonasal Tract.

Low-grade epithelial proliferations of the sinonasal tract include Schneiderian papillomas, respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma and low-grade non-intestinal adenocarcinoma. There is considerable overlap in their clinical presentation, endoscopic appearance, and imaging features. Although well-described diagnostic criteria exist, a definitive diagnosis may be difficult to reach on a small biopsy. Schneiderian papillomas are divided into fungiform, inverted, and oncocytic types, each with characteristic clinical and morphological features. The latter two may progress to malignancy. The majority are still considered to be HPV-related. Two lesions are designated as hamartomas, but their pathogenesis remains uncertain, with inflammatory and neoplastic origins proposed. Respiratory epithelial adenomatoid hamartoma is increasingly being recognized for its association with chronic rhinosinusitis and olfactory cleft site of origin. Seromucinous hamartoma has gained attention in recent years and overlaps with both respiratory epithelial adenomatoid hamartoma and low-grade non-intestinal adenocarcinoma. Controversy surrounds their distinction, particularly from low-grade adenocarcinoma. The latter generally is cured by complete excision, with a 26% risk of recurrence but rare metastases and deaths from disease.

CK7, CK20, SOX10 and CDX2: expressions and diagnostic values in primary adenocarcinoma of the sinonasal tract

To explore the expressions of the cytokeratin 7 (CK7), cytokeratin 20 (CK20), SOX10 and cadual type homeobox transcription factor 2 (CDX2) in primary adenocarcinoma of the sinonasal tract, and evaluate their diagnostic values. A total of 41 paraffin-embeded specimens of primary adenocarcinoma of the sinonasal tract treated in Beijing Tongren Hospital of Capital Medical University were selected from May 2002 to January 2015. All cases were confirmed by histology and clinical data, including 12 cases of non-intestinal sinonasal adenocarcinomas (non-ITACs), 10 cases of intestinal sinonasal adenocarcinomas (ITACs) and 19 cases of salivary gland-type adenocarcinomas (including 12 cases of adenoid cystic carcinomas, 3 cases of polymorphous low grade adenocarcinomas, 2 cases of mucinous adenocarcinomas and 2 cases of acinar cell carcinomas). Expressions of CK7, CK20, SOX10 and CDX2 were assessed by immunohistochemistry staining method. Nuclear staining for CDX2 was identified in all the ITACs,including diffuse nuclear staining in 8 cases and partial nuclear staining in 2 cases. Cytoplasmic staining for CK20 was identified in 9 cases of ITACs, and partial cytoplasmic staining was found in 1 case of non-ITACs, while CK20 was negative in all other adenocarcinomas.Seven cases of ITACs were negative for CK7, while CK7 was positive in all other adenocarcinomas. CK7, but not CDX2 and CK20, was expressed in normal sinonasal epithelium. SOX10 was negative in 10 cases of ITACs and 2 cases of non-ITACs, and positive in all other adenocarcinomas. The sensitivity of CK7-, CK20+, SOX10- and CDX2+ in primary ITACs of the sinonasal tract were 70.0%, 90.0%, 100%, 100%, respectively, and the specificity were 100%, 96.8%, 93.5%, 100%, respectively. Expressions of CK7-, CK20+, SOX10- and CDX2+ have high sensitivity and specificity in ITACs and can be used as a reliable diagnostic marker for primary intestinal-type adenocarcinoma of the sinonasal tract. Additionally, diagnostic value of CDX2 in primary intestinal-type adenocarcinoma of the sinonasal tract is superior to CK20, CK7 and SOX10.

SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract.

SMARCB1 (INI-1) is a tumor-suppressor gene located on chromosome 22q11.2. Its gene product is ubiquitously expressed in nuclei of all normal tissues. SMARCB1 gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" cytomorphology. This group of SMARCB1-deficient tumors is now further expanded by a subset of carcinomas arising in the sinonasal tract. SMARCB1 immunostaining was performed on 142 sinonasal carcinomas. Tumors that showed loss of expression were further characterized for SMARCB1 deletions by fluorescence in situ hybridization. Nine of 142 (6%) primary sinonasal carcinomas showed loss of SMARCB1 expression by immunohistochemistry. Five patients were women, and patients ranged in age from 33 to 78 years (mean 59 y). The SMARCB1-deficient tumors were characterized by nests, sheets, and cords of cells without any histologic evidence of specific (eg, squamous or glandular) differentiation. The tumors comprised varying proportions of basaloid and rhabdoid cells. The SMARCB1-deficient carcinomas had been diagnosed as nonkeratinizing squamous cell carcinomas (n=3), sinonasal undifferentiated carcinomas (n=2), myoepithelial carcinoma (n=2), nonintestinal adenocarcinoma (n=1), and carcinoma, not otherwise specified (n=1). Fluorescence in situ hybridization analysis revealed SMARCB1 deletions in 6 of 8 (75%) carcinomas. The SMARCB1-deficient carcinomas did not harbor human papillomavirus or NUT-1 alterations. Six patients presented with T4 disease, 5 patients developed local recurrences and/or distant metastases, and 4 died of their disease. Inactivation of the SMARCB1 tumor-suppressor gene appears to be involved in the pathogenesis of a subset of sinonasal carcinomas, further expanding the family of SMARCB1-deficient neoplasms and further delineating a bewildering group of poorly/undifferentiated, aggressive carcinomas arising at this site. The ability to detect SMARCB1 loss by immunohistochemistry, particularly when dealing with poorly differentiated carcinomas with basaloid or rhabdoid features, should facilitate a more comprehensive understanding of these sinonasal carcinomas including clinical behavior and response to targeted therapies.

Genetic Similarities between Ethmoidal Adenocarcinoma and Colorectal Adenocarcinoma: Towards a New Targeted Therapy?

Background: To compare the genetic profile and phenotype of sinonasal Intestinal Type AdenoCarcinoma (ITAC) and colorectal adenocarcinoma. Methods: Between 1983 and 2001, 41 patients were treated for ethmoidal adenocarcinoma at Rouen University Hospital. All pathologic specimens were reassigned according to the new 2005 World Health Organization classification. Immunohistochemical study was carried out to evaluate EGFR and CDX2 expression. Thirty-eight out of the 41 tumor specimens had sufficient DNA for KRAS and EGFR mutation analysis. SNaPshot® multiplex system was used to determine presence of the most common mutations (located in exons 18, 19, 20 and 21 for EGFR and in exon 2 [codon 12 and 13] for KRAS). Results: Of the 41 patients, there were 37 men and four women. Mean age at presentation was 63.6 years (range: 40.7-86.4 years). Occupational exposure was documented for 32 patients, with 31 cases of wood exposure and one of leather exposure. Of the 38 tumors genotyped, 35 were ITAC (33 men and two women) and wood exposure was found in 29 (85%) of these patients. CDX2 expression was present in 31 out of the 35 ITAC (89%) and absent in the 3 non-intestinal adenocarcinomas. EGFR was expressed in 29 out of the 35 ITAC (83%) with different expression: 19 (56 %) 1+, 7 (21%) 2+ and 3 (6%) 3+ immunopositivity and the 3 non ITAC disclosed 1+ EGFR positivity. No EGFR mutation was found in the series. For KRAS, 5 out of the 35 ITAC (14%) disclosed KRAS exon 2 mutation and the 3 non-intestinal adenocarcinomas were KRAS wild type. Conclusion: CDX2 immunohistochemistry could be a useful tool for discriminating ITAC. Phenotype and genotype similarities between ITAC and colorectal carcinomas could lead to clinical trials using anti-EGFR therapy in patients with locally advanced or metastatic ITAC.

Sinonasal undifferentiated carcinoma and esthesioneuroblastoma recurring as nonintestinal adenocarcinoma

Numerous distinct neoplasms are encountered at the anterior cranial base. Management of these primary tumors and their locoregional recurrences are dictated by the histopathologic diagnosis. We present two unusual cases of extra-axial anterior cranial base malignancies with locoregional recurrence where the recurrent tumor encountered was of a distinct histopathologic type. While rare, this report highlights the possibility of encountering a distinct tumor type in the posttreatment surveillance of patients with anterior cranial base malignancies.

A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas

A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas

A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas

Nonintestinal sinonasal adenocarcinomas (SNACs) are somewhat poorly characterized and high-grade nonintestinal SNACs have been only rarely reported. Here, we review our experience with these tumors. Twenty-seven cases of high-grade nonintestinal SNACs were identified from 22 men and 5 women. Ages ranged from 22 to 83 years (mean±1 standard deviation=54.7±18.6 y; median=60 y). Thirteen cases involved the nasal cavity and sinuses, 10 involved the nasal cavity only, and 4 involved sinuses only. Most cases had marked cytologic and nuclear pleomorphism, abundant mitotic activity, and necrosis; however, these features were not uniform. Although histologically heterogeneous, recurrent growth patterns were seen that resembled other neoplasms of the area. Tumors lacked CDX2 and CK20 immunoreactivity (aside from rare CK20 immunoreactive cells). High-grade nonintestinal SNACs are more common in men and, although they occur over a wide age range, they are much more common in older individuals. Histologically, they show a great deal of heterogeneity.

Adenocarcinoma of the Upper Aerodigestive Tract

Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low-grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed.

Adénocarcinomes des fosses nasales et des sinus : pièges diagnostiques des lésions glandulaires naso-sinusiennes

Among primitive adenocarcinoma of nasal cavity and paranasal sinus, the 2005 WHO classification distinguishes two main categories: intestinal type adenocarcinoma (ITAC) and low-grade non-intestinal adenocarcinoma, entities with different clinical and epidemiological characteristics. Low-grade adenocarcinoma shows a respiratory type phenotype (CK20-/CK7+/CDX2-/villin-) and ITACs, an intestinal type profile (CK20+/CK7-/CDX2+/villin+). Because of histological, ultrastructural and phenotypical similarities between ITAC and colorectal adenocarcinomas, several studies have discussed a possible common pathway in carcinogenesis. But the review of literature shows conflicting results, suggesting different pathways of pathogenesis. Differential diagnoses of sinonasal intestinal-type adenocarcinoma are mainly respiratory epithelial adenomatoid hamartomas, inverted schneiderian papillomas, salivary glands-type carcinoma and more rarely metastasis of adenocarcinoma.

Role of CDX2 immunostaining in diagnosis of gastrointestinal adenocarcinoma

To study the expression of CDX2 in normal and tumor tissues, and to evaluate the value of CDX2 immunostaining in the diagnosis of gastrointestinal adenocarcinoma. Seventy-six samples of normal tissue and 612 samples of tumor tissue were studied by tissue microarray technology and immunohistochemistry for CDX2. CDX2 was strongly expressed in surface epithelium of 13 samples of normal intestine and in ductal epithelium of 8 samples of normal pancreas, as well as in 47 samples (92.2%) of colonic adenocarcinoma and 58 samples (66.9%) of gastric adenocarcinoma. As for other tumor types, there was only weak or patchy CDX2 positivity. The positivity rates were as follows: ovarian mucinous adenocarcinoma 15.6% (10/64), pancreatic cancer 33.3% (3/9), thyroid cancer 27.3% (3/11) and extrahepatic biliary cancer 25% (4/16). On the other hand, primary tumors of breast, prostate, kidney, adrenal and liver were negative for CDX2. CDX2 is expressed mainly in normal epithelium of intestinal tract and small pancreatic ducts, as well as in primary adenocarcinoma of gastrointestinal tract. CDX2 may thus play an important role in distinguishing primary non-intestinal adenocarcinoma from metastatic adenocarcinoma of gastric or colorectal primary.

Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2.

Nonsalivary sinonasal adenocarcinomas can be divided into low-grade and high-grade tumors. The former are often papillary and the latter are usually of intestinal type, morphologically similar to metastatic colonic carcinoma. Antibodies to CDX2, a transcription factor gene highly specific for intestinal adenocarcinomas, MUC2, a mucin gene expressed in adenocarcinomas from various sites, and cytokeratins (CK) 7 and 20 were used to examine the two groups of tumors. Formalin-fixed, paraffin-embedded tissue from 22 sinonasal adenocarcinomas was reclassified into 9 high-grade intestinal-type, 3 high-grade nonintestinal, and 10 low-grade, predominantly papillary adenocarcinomas. Immunohistochemical staining was graded on a 0 to 4+ scale with 5% or greater tumor cell staining considered positive. Of the high-grade intestinal group, 78% demonstrated 4+ CDX2 positivity, with 44% MUC2 positive. Although 89% of this group was CK7 positive, the percent of staining was variable. A majority (67%) of the intestinal cases was 4+ CK20 positive. Almost every nonintestinal adenocarcinoma (90%) (low- and high-grade) was CK7 positive (7 of 9, 4+), without expression of any of the three colonic adenocarcinoma markers. The three high-grade nonintestinal tumors had the expression profile of the low-grade papillary group with the exception of focal MUC2 positivity in 1 case. Intestinal-type adenocarcinomas have an expression profile distinct from nonintestinal sinonasal adenocarcinomas. The former are similar, but not identical, to colonic adenocarcinomas. Immunohistochemical staining for CDX2, MUC2, and differential cytokeratins does not differentiate metastatic colorectal from primary sinonasal intestinal-type adenocarcinoma.