bromochloroacetic-acid and Neuroendocrine-Tumors

A rare case of pancreatic neuroendocrine neoplasm in a patient with tuberous sclerosis complex is described. The patient was a 31-year-old man who had multiple congenital subependymal nodules, bilateral cortical tubers, and seizures of difficult control. A 2.3 cm × 2 cm well-delimitated solid tumor in the tail of the pancreas was discovered during a monitoring abdominal computed tomography. A distal pancreatectomy was performed. Histologically, the tumor was formed by uniform cells with moderated cytoplasm arranged in a combined trabecular and nested pattern. The nuclear features were bland, and mitosis was infrequent. There was no vascular invasion. Immunoreactivity for cytokeratine AE1/AE3, chromogranin A, and synaptophysin confirmed the neuroendocrine nature of this neoplasia. Pancreatic hormones were negatives. One of the 5 lymph nodes isolated from the peripancreatic adipose tissue was positive for metastases. Small series and case reports have documented that in tuberous sclerosis many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid, and other neuroendocrine tissue, including islet cells of the pancreas. However, the true association of these pathological conditions remains uncertain. As far as we know, there are 10 cases reported of pancreatic neuroendocrine tumors in a setting of tuberous sclerosis complex, in which 2 cases resulted in malignant, nonfunctioning pancreatic neuroendocrine tumors.

Topics: Adult; Biomarkers, Tumor; Chromogranin A; Humans; Keratins; Lymphatic Metastasis; Male; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Neoplasms; Synaptophysin; Tuberous Sclerosis

Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.

Topics: Combined Modality Therapy; Diagnosis, Differential; Humans; Keratins; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroendocrine Tumors; Prognosis; Radiography; Thymus Neoplasms

Endocrine tumors constitute a large group of neoplasms that are widely dispersed throughout the body. They are made up mostly of neuroendocrine tumors (NE), which are characterized by the presence of secretory granules and production of peptide hormones, and non-NE tumors such as those derived from thyroid follicular cells and adrenal cortical cells. Immunohistochemical markers have been used to characterize these lesions and distinguish them from other histologically similar tumors. Chromogranin and synaptophysin are the most widely used broad-spectrum neuroendocrine tumor markers. The use of antibodies to transcription factors, keratins, and specific peptides is quite valuable in the diagnosis of endocrine tumors. This article reviews the common markers used to characterize endocrine tumors and to recognize tumors involved in the differential diagnosis of specific lesions.

Topics: Biomarkers, Tumor; Chromogranins; Diagnosis, Differential; Endocrine Gland Neoplasms; Humans; Immunohistochemistry; Keratins; Neuroendocrine Tumors; Synaptophysin; Transcription Factors

Although there are many broad-spectrum neuroendocrine markers, chromogranin and synaptophysin are the principal ones used in diagnostic pathology. Other broad-spectrum neuroendocrine markers, transcription factors, and specific peptide markers used in the diagnosis of neuroendocrine tumors are reviewed. The use of different keratins in the differential diagnosis of endocrine tumors is also presented. The importance of using low-molecular-weight keratins such as CAM5.2 to avoid false-negative results in the workup of some neuroendocrine tumors is emphasized. Finally, the use of in situ hybridization in diagnostic pathology is briefly summarized.

Topics: Aged; Biomarkers, Tumor; Chromogranins; Diagnosis, Differential; Humans; In Situ Hybridization; Keratins; Male; Neuroendocrine Tumors; Neurosecretory Systems; RNA, Messenger; Synaptophysin; Transcription Factors

Topics: Antigens, Nuclear; Biomarkers, Tumor; Cell Differentiation; Cell Division; DNA Mutational Analysis; DNA, Neoplasm; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nerve Tissue Proteins; Neuroendocrine Tumors; Nuclear Proteins; Protein Isoforms; Receptors, Cell Surface; Terminology as Topic; World Health Organization

The problems with classification and diagnosis of bronchopulmonary carcinoid and other neuroendocrine tumors are described in this paper. Single neuroendocrine cells and so-called neuroepithelial bodies found in normal bronchial epithelium are currently believed to constitute pulmonary components of an extensive neuroendocrine system. In view these opinions, it has appeared a need for a new, standardized nomenclature. Hence presently suggested classification of neuroendocrine carcinomas taking into account their histological structure, immunohistochemical as well as prognostic features starting from carcinoid tumors to small cell anaplastic carcinomas-includes three types of neoplasms.

Topics: Biomarkers, Tumor; Bronchial Neoplasms; Carcinoid Tumor; Carcinoma, Neuroendocrine; CD57 Antigens; Cell Size; Chromogranin A; Chromogranins; Humans; Keratins; Lung Neoplasms; Neoplasm Proteins; Neuroendocrine Tumors; Neuropeptides; Phosphopyruvate Hydratase; Silver Staining; Somatostatin; Synaptophysin; Terminology as Topic

The tumor formerly known as "cauda equina paraganglioma" was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. Nevertheless, it remains insufficiently understood. For this study, we retrieved CENETs (some previously reported), from the pathology files of 3 institutions; we examined their immunohistochemical profile, including common neuroendocrine tumor-associated hormones and transcription factors. We identified 24 CENETs from 7 female and 17 male adult patients, with a median age of 47 years. Six included neurofilament-positive ganglion cells. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2); CK7 and CK20 were negative. Glial fibrillary acidic protein was negative, except for peripheral nontumoral elements. S100 protein was variable but mainly expressed in scattered sustentacular cells. All but 1 tumor tested were positive for HOXB13; several stained for SATB2, and all tumors were consistently negative for GATA3. All tumors tested were negative for transcription factors found in various other epithelial neuroendocrine neoplasms including TTF1, CDX2, PIT1, TPIT, SF1, and PAX8; staining for T-brachyury was negative. Four of 5 CENETs tested had at least focal tyrosine hydroxylase reactivity. Serotonin expression was detected in all 21 tumors tested; it was diffusely positive in 5 and had variable positivity in the remainder. A few tumors had scattered cells expressing gastrin, calcitonin, pancreatic polypeptide, and peptide YY, while glucagon, adrenocorticotropic hormone, and monoclonal carcinoembryonic antigen were negative. PSAP expression was found focally in 4 of 5 tumors examined. SDHB was consistently intact; ATRX was intact in 14 tumors and showed only focal loss in 3. The median Ki-67 labeling index was 4.5% (range: 1% to 15%). We conclude that CENET represents a distinct neuroendocrine neoplasm; the subset with ganglion cells qualifies for designation as composite gangliocytoma/neuroma-neuroendocrine tumor (CoGNET) as defined in the 2022 WHO classification of neuroendocrine neoplasms. In addition to INSM1, chromogranin, synaptophysin, and keratins, the most characteristic finding is nuclear HOXB13 expression; a subset also express SATB2. Serotonin is the most common hormone expressed. The cytogenesis and pathogenesis of these lesions remains unclear.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Cauda Equina; Female; Humans; Keratins; Male; Middle Aged; Neuroendocrine Tumors; Paraganglioma, Extra-Adrenal; Repressor Proteins; Serotonin; Synaptophysin; Transcription Factors

Paragangliomas are rare neuroendocrine tumors originating from neural crest-derived paraganglion cells. Primary cauda equina paraganglioma (CEP) pose both diagnostic and surgical challenges. We report 12 cases of CEP to characterize the diagnostic and operative approach to these rare tumors. 12 cases with primary CEP were studied; 5 patients were male (41.7%) and 7 were female (56.3%). The median age was 44 years (range: 15-64 years). The most common symptom was lower back pain of variable duration. Radiologically, the lesions were intradural and extramedullary with well-defined margins, and ranged from 1 to 4.5 cm. in diameter (mean: 1.65 cm). 9 tumors were composed of sheets and nests of cells with a neuroendocrine pattern and intense vascularity and displayed a characteristic Zellballen pattern. Interestingly, CAM 5.2 was diffusely or focally positive with a dot-like or membrane pattern in 8/11 cases (72.7%). Similarly, CK was diffusely or focally positive with membrane and cytoplasmic staining or with a dot-like pattern in 7/11 (63.6%) and 2/11 cases (18.2%). None of the cases showed deletion of SDHB nor expression of GATA3. CEP can display aberrant keratin positivity, and this should be considered in the differential diagnosis of these lesions. This finding also raises the possibility that CEP may be an entirely different entity than non-spinal paragangliomas.

Topics: Adult; Cauda Equina; Female; Humans; Keratins; Male; Neuroendocrine Tumors; Paraganglioma; Peripheral Nervous System Neoplasms

The extrahepatic biliary apparatus is a rare site for neuroendocrine tumours. A 13-year-old child presented with cholestatic symptoms of jaundice and pruritus with soft hepatomegaly and mild ascites. Magnetic resonance imaging and endoscopic ultrasound revealed a mid-common bile duct mass, and dilated intrahepatic biliary system. An en-bloc resection of the extrahepatic biliary apparatus, showed malignant cells disposed in lobules in a desmoplastic stroma with intramural invasion, staining positive for cytokeratin, chromogranin, synaptophysin and negative for CD56. At 3 months post-resection, whole body positron emission tomography scan was normal with no recurrence at 24 months.

Topics: Adolescent; Child; Chromogranins; Common Bile Duct; Humans; Jaundice, Obstructive; Keratins; Neuroendocrine Tumors; Synaptophysin

The presence and patterns of keratins are critical in the classification of pituitary neuroendocrine tumors. A large body of literature has included information about the staining patterns of pituitary tumors and tissues with the CAM 5.2 antibody. During an antibody validation for clinical use, we carried out staining of a series of 29 surgically resected pituitary cases containing 31 pituitary neuroendocrine tumors that were tested for CAM 5.2 as well as for cytokeratin (CK) 7, 18, 19, and 20 and the pan-keratin cocktail AE1/AE3. The results showed an almost identical staining pattern for CK18 and CAM 5.2; however, CAM 5.2 yielded more intense staining, whereas CK18 provided more delicate results. Staining results using AE1/AE3 were satisfactory but generally less intense; however, this marker was more specific, identifying keratin expression in one tumor that was negative with CAM 5.2. CK19 is expressed in nontumorous adenohypophysis but was less frequently positive in tumors; somatotroph and corticotroph tumors were negative for CK19, but CK19 antibody highlighted follicular cells in some gonadotroph tumors. CK7 and CK20 were negative in all pituitary tissues tested. Our findings underscore the role for CAM 5.2 and CK18 as the most valuable to identify specific alterations in adenohypophysial cells and their tumors; there is also a role for AE1/AE3 to verify the epithelial nature of pituitary neuroendocrine tumors that are negative for CAM 5.2 and CK18.

Topics: Biomarkers, Tumor; Humans; Keratins; Neuroendocrine Tumors; Pituitary Neoplasms

To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis.. We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin.. E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.. E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Topics: Adult; Aged; alpha 1-Antitrypsin; Antigens, CD; beta Catenin; Cadherins; Carcinoma, Papillary; Chromogranin A; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neprilysin; Neuroendocrine Tumors; Pancreatic Neoplasms; Receptors, Progesterone; Synaptophysin; Vimentin; Young Adult

Pancreatic neuroendocrine tumors are a rare subset of pancreatic neoplasms. We report the case of a 33-year-old female patient who was admitted to the Diabetes Clinic of Craiova, Romania, due to a two-year history of episodic neuroglycopenic hyperinsulinemic hypoglycemic symptoms, suggestive for insulinoma associated with facial and upper trunk flushing characteristic to carcinoid syndrome. During these episodes, the laboratory investigations showed hypoglycemia (38 mg/dL), hyperinsulinemia (54.72 μU/mL) and normal values of beta-hydroxybutyrate, chromogranin A, serotonin, anti-insulin antibodies and urinary levels of 5-hydroxyindoleacetic acid. Endoscopic ultrasound with SonoVue and 3T MRI revealed an 18.3/16.3 mm hypervascular tissular mass situated in the uncinate process of the pancreatic head in close contact with the superior mesenteric vein without invasion and no other detectable secondary lesions in the pancreas or any other abdominal viscera. Patient underwent enucleation of pancreatic tumor. The histological and immunohistochemical findings indicated a functional well-differentiated pancreatic neuroendocrine tumor, G1 category according to the World Health Organization (WHO) criteria, with uncertain behavior (Ki67 index was 3%), confined to the pancreas, but with tumoral invasion of the delimiting conjunctive capsule. No evidence of tumoral CK19 staining, mitoses and necrosis, angioinvasion or extra-pancreatic invasion was observed. A post-operative nine-month follow-up showed resolution of hypoglycemic symptoms, normalized blood glucose and insulin levels and no evidence of recurrence. Our case report highlights the pitfalls in diagnosing a functional pancreatic neuroendocrine tumor due to atypical symptoms, the difficulty of identification and precise location of the small-size tumor and uncertain histopathological and immunohistochemical behavior.

Topics: Adult; Antigens, CD34; Endoscopy; Female; Humans; Immunohistochemistry; Intraoperative Care; Keratins; Magnetic Resonance Imaging; Neuroendocrine Tumors; Pancreatic Neoplasms; Ultrasonography, Doppler

Topics: Adenoma; Ear Neoplasms; Ear, Middle; Female; Hearing Loss, Conductive; Humans; Immunohistochemistry; Keratins; Middle Aged; Neuroendocrine Tumors; Otologic Surgical Procedures; Synaptophysin; Tinnitus

Chromogranin A (CgA) is the most important tumour marker for well-differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for poorly differentiated neuroendocrine carcinoma (NEC). This study investigated whether the markers progastrin-releasing peptide (proGRP) and cytokeratin fragments (CKfr) CK8, CK18 and CK19 (MonoTotal) can be of additional value to the histological classification and help predict survival in these patients.. CgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET), 38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell NEC (SCNEC) and in 282 healthy persons. Results were compared with tumour characteristics and survival by means of Receiver Operating Characteristics (ROC) curves and Cox regression analyses.. The largest area under the ROC curve was for CgA (0.86, 0.91 and 0.90, respectively) when comparing patients with G1NET, G2NET and LCNEC with healthy persons. ProGRP showed the highest sensitivity (73%) at 95% specificity in patients with SCNEC. In a multivariate survival analysis, only CKfr was associated with survival (P<0.0001) for patients with well-differentiated NET (G1NET and G2NET). For patients with poorly differentiated NEC, both CKfr and NSE were associated with survival (P<0.0001 and P=0.003, respectively).. Within all histological groups a combination of tumour markers proved to be more informative as diagnostic and prognostic marker than each marker alone. In patients with well-differentiated NET and LCNEC we recommend the use of CgA and CKfr, whilst in patients with SCNEC, proGRP and CKfr are preferred.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Chromogranin A; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Grading; Neuroendocrine Tumors; Peptide Fragments; Phosphopyruvate Hydratase; Recombinant Proteins; ROC Curve; Survival Analysis; Young Adult

(1) To test whether in genomewide expression profiling differentially expressed genes were also distinct on the protein level including KIT and PDGFRA (2) to correlate the expression with clinicopathological parameters (3) to identify activating mutations that might be eligible for tyrosine kinase inhibitor therapy by mutational analysis of tumors with high expression.. Gastroenteropancreatic neuroendocrine tumors (GEP NETs) from 119 patients were analyzed for protein expression of ten biomarkers. Mutational analysis of KIT (exon 9, 13, 11 and 17) and PDGFRA (exons 12 and 18) was performed on those samples that showed high protein expression.. High KIT expression was observed in 13% of all specimens, PDGFRA in 33%, CK19 in 26%, CK7 in 2%, CK20 in 5%, S100 in 6%, CD56 in 25%, Chromogranin in 55%, and Synapthophysin in 80%. High expression of KIT and PDGFRA was significantly correlated with shorter disease-specific survival (P = 0.003, P = 0.018, respectively). In multivariate analysis expression of PDGFRA, radicality of surgical treatment and WHO grading influenced disease-specific 10-year survival independently (P = 0.032, P = 0.001 and P = 0.008, respectively). Mutational analysis of highly expressed specimens (n = 51) reveals a novel mutation of KIT in exon 11 (K558N_V559insP) in a well-differentiated metastatic pancreatic neuroendocrine tumor.. High expression of KIT and PDGFRA was significantly correlated with shorter patients survival and could serve as prognostic marker. Mutations of the KIT gene might open new avenues for tyrosine kinase inhibitor therapy in a subset of patients with advanced pancreatic neuroendocrine tumors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CD56 Antigen; Chromogranin A; Digestive System Neoplasms; DNA Mutational Analysis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intestinal Neoplasms; Kaplan-Meier Estimate; Keratins; Ki-67 Antigen; Male; Middle Aged; Mutation; Neuroendocrine Tumors; Odds Ratio; Pancreatic Neoplasms; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; S100 Proteins; Stomach Neoplasms; Synaptophysin; Up-Regulation

Topics: Adenocarcinoma, Clear Cell; Aged; Antimetabolites, Antineoplastic; Arm; Biomarkers; Biomarkers, Tumor; Deoxycytidine; Diagnostic Errors; Female; Gemcitabine; Humans; Keratins; Neoplasm Proteins; Neprilysin; Neuroendocrine Tumors; Pancreatic Neoplasms; Phosphopyruvate Hydratase; Soft Tissue Neoplasms; Subcutaneous Tissue; Vimentin

Neuroendocrine (NE) cells increase in high grade/stage prostate cancer (PC) and may contribute to androgen-independent cancer. Their immunohistochemical phenotype has not been studied in detail and conflicting results have been reported.. PC tissue was stained immunohistochemically for luminal secretory cell-associated cytokeratin, basal cell markers, ki-67, androgen receptor (AR), PSA, prostate acid phosphatase (PAP), and alpha-methylacyl coenzyme A racemase (AMACR).. The NE cells are positive for AE1/AE3, Cam 5.2, and negative for basal cell markers. They are negative for AR, PSA, and Ki-67 but positive for PAP. The benign NE cells are negative for AMACR while the malignant NE cells are positive for AMACR.. NE cells of PC constitute a unique subset of cancer cells, which have a unique immunohistochemical profile. They do not express AR, consistent with their resistance to hormonal therapy. They are post-mitotic cells but are malignant and part of the tumor.

Topics: Acid Phosphatase; Androgen Antagonists; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Neuroendocrine Tumors; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases; Receptors, Androgen

We selected a 4-stain immunopanel including thyroid transcription factor (7ITF)-], cytokeratin (CK)7, 34betaE12, and CD56/neural cell adhesion molecule(NCAM) to subclassify a series of 45 pulmonary large cell carcinomas (LCCs) on bronchial biopsy. All cases consisted of a large tumor cell proliferation with abundant cytoplasm, vesicular nuclei, and prominent nucleoli. Immunohistochemically, 27 tumors (60%)were subclassified as adenocarcinoma (7TF-1 +/CK7+,24; CK7+ only, 3), 10 (22%) as squamous cell carcinoma (34betaE12+ only), and 4 (9%) as LCC with neuroendocrine differentiation (CD56+, variably stained with TTF-I and CK7, 34betaE12-). In 4 cases, the tumors coexpressed CK7 and 34betaE12 (3 cases) or were completely unstained (I case). Surgically resected tumors matched exactly with the corresponding original biopsy specimens in 21 of 23 cases; consistent CD56 expression was a reliable marker in confirming a diagnosis of large cell neuroendocrine carcinoma even on biopsy. Our results suggest that the proposed 4-stainset of commercially available markers might help subclassify LCC even in small biopsy material, validating expression-profiling studies aimed at lung cancer classification and permitting more consistent patient enrollment for trials with targeted treatments.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Nuclear Proteins; Thyroid Nuclear Factor 1; Transcription Factors

We conducted a retrospective clinicopathologic and immunohistochemical study of the biologic significance of mesoappendix infiltration in 15 appendiceal neuroendocrine tumors selected from a series of 42 primary tumors. In all cases, the tumor was found incidentally and measured less than 2 cm (mean, 0.84 cm). In 13 cases, it was located in the tip of the appendix and in the midportion in 2. Histologically, none showed relationship with overlying mucosa. Necrosis was absent; mitotic figures were rare. The Ki-67 labeling index was low (1%-2%). In all cases, S-100 protein immunostaining disclosed positive elements with cytoplasmic dendritic processes closely intermingled with neuroendocrine neoplastic cells. All patients (8 males; 7 females; mean age, 38.2 years) underwent simple appendectomy. A right-sided hemicolectomy was performed subsequently in 1 case. After a mean follow-up of 52.6 months (range, 8-143 months), none had died of disease or had recurrent or metastatic disease. Our results confirm that appendiceal neuroendocrine tumors seem to have a different phenotype from those occurring in other gastrointestinal sites. Tumors less than 2 cm, even with mesoappendiceal infiltration, have an excellent prognosis, and simple appendectomy seems to be the appropriate therapeutic approach.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Appendiceal Neoplasms; Appendix; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neuroendocrine Tumors; Prognosis; S100 Proteins

Neuroendocrine (NE) carcinomas of the breast share morphologic and immunohistochemical features with NE tumors of other sites, either resembling typical carcinoids or the highly aggressive small cell carcinoma. In addition, some mucinous carcinomas or solid/papillary carcinomas may show a major NE component. This is generally recognized by specific immunodetection of pan-endocrine markers, although this approach may fail to recognize NE tumors lacking immunoreactivity for some NE products, because the antigen is produced but not retained in the cytoplasm. It has recently been reported that high molecular weight (HMW) cytokeratin (CK), recognized by clone 34betaE12, immunostaining selectively labels non-NE carcinomas (squamous-cell and adenocarcinomas) of the aerodigestive tract and lung. The role of such CK immunodetection in the differential diagnosis of NE carcinoma of the breast was evaluated. Twenty-four cases of breast carcinomas having NE differentiation were selected. Twenty-four cases of non-NE invasive breast carcinomas served as controls. HMW CK immunoreactivity was found in all but one case of non-NE carcinomas, but in only two NE tumors (having scattered positive cells only). The authors conclude that in breast carcinomas the presence of HMW CK immunoreactivity favors the diagnosis of non-NE carcinoma, whereas its absence supports that of a NE tumor (either a carcinoid or a small cell carcinoma or a mucinous carcinoma). HMW CK can be added to the list of markers useful in the differential diagnosis of NE from non-NE tumors.

Topics: Biomarkers, Tumor; Breast Neoplasms; Diagnosis, Differential; Humans; Keratins; Molecular Weight; Neuroendocrine Tumors

Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival.. CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Molecular Weight; Neuroendocrine Tumors