Tertiary Lymphoid Structures, Immune Response, and Prognostic Relevance in Non-Small Cell Lung Cancer.

We assessed the presence of 'tertiary lymphoid structures' (TLS) in a series of surgically treated non-small cell lung carcinomas (NSCLC). The TLS-density in the tumor periphery (pTLS) ranged from 0 to 1.8 (median 0.45), while in inner tumor areas (iTLS) ranged from 0 to 1.0 (median 0); (p < 0.0001). High pTLS-density was linked with early stage of the disease. Glycolysis-related enzyme expression (MCT1, Hexokinase 2) was linked with high pTLS-density (p < 0.05). High pTLS and iTLS densities were linked with better postoperative prognosis (p = 0.02 and p = 0.01, respectively). Assessment of TLS is a useful prognostic marker in NSCLC.

Double appendixes: A rare case report.

Anomalies of the appendix are rare, and one of the rarest is the double appendixes. Most anomalies of the appendix are observed in adults and are discovered incidentally during surgery that does not primarily involve the appendix. It is usually missed, often with life-threatening consequences.

Endometrial Stromal Expression of ER, PR, and B-Catenin Toward Differentiating Hyperplasia Diagnoses.

Background. The interpretation of histopathological changes of endometrial hyperplasia with or without atypia can be challenging. We aim to investigate the role of specific immunohistochemical markers in the endometrial stroma to classify endometrial hyperplasia in difficult cases. Methods and Results. We retrospectively reviewed and reclassified (WHO 2014): 47 specimens with endometrial hyperplasia without atypia, 33 with atypical hyperplasia (AH), and 13 endometrioid adenocarcinomas. We performed IHC for B-catenin, E-cadherin, p16, estrogen receptors and progesterone receptors, and B-cell lymphoma 2 (BCL2). Percentage of positive stromal cells was calculated. B-catenin was equally expressed in the stroma of both hyperplasia and AH (mean 60%, 50%; P = .17) and was absent from adenocarcinoma (0%, hyperplasia vs adenocarcinoma; P < .0001, AH vs adenocarcinoma; P < .0001). E-cadherin was not expressed in the stroma of any lesion, while p16 expression levels were not statistically different (hyperplasia vs AH; P = .46, hyperplasia vs adenocarcinoma; P = .22, AH vs adenocarcinoma; P = .48). Estrogen and progesterone were highly identified in stromal cells of hyperplasia (80%) and diminished in AH (respectively, at 30% and 60%, hyperplasia vs AH; P < .0001), and in adenocarcinoma (0% and 40%, respectively). Finally, BCL2 was not differentially expressed (hyperplasia vs AH; P = .33, hyperplasia vs adenocarcinoma; P = .17, AH vs adenocarcinoma; P = .36). Conclusion. Estrogen and progesterone were strongly expressed in stroma exclusively of hyperplasia, while B-catenin was particularly expressed in hyperplasia and AH. Use of these markers can be useful in the differential diagnosis of hyperplasia from AH, and AH from adenocarcinoma in challenging cases.

Any Etiquette for Sacrococcygeal Chordoma's Diagnosis?

The current paper focuses on a trial to understand the imaging manifestations in combination with the clinical presentation of the sacrococcygeal chordoma in a patient with referred back pain. Also, the steps for the final diagnosis are described and via this procedure, the paper demonstrates the crucial role of magnetic resonance imaging, computed tomography guided biopsy and histopathological examination in order to minimize the differential diagnosis and lead to the correct diagnosis.

Dermatofibrosarcoma protuberans in a child, that's why soft tissue lesions are not always innocent in children.

Pediatric soft tissue tumors should be always operated and sent for a biopsy.

Early histopathologic changes in primary biliary cholangitis: does 'minimal change' primary biliary cholangitis exist? A pathologist's view.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune, slowly progressive, cholestatic liver disease characterized by nonsuppurative destructive cholangitis, and interlobular bile duct destruction. Necroinflammatory activities of the hepatic parenchyma and limiting plates of milder form along with late liver fibrosis may develop. Serum liver tests include elevated serum alkaline phosphatase along with a positive antimitochondrial antibody (AMA) in nearly 95% of patients. Liver biopsies are an important confirmatory and staging tool and are additionally very helpful when AMA is negative. More specifically, the earliest changes in liver biopsy suspicious for PBC can be detected, namely loss of the canals of Hering (CoH), as proposed by various authors recently. CoH loss has been described as an early feature of PBC. We focus on early histologic features of PBC, investigating through the literature the possible role of 'minimal change' supporting the clinical diagnosis of PBC, even in the absence of characteristic granulomatous duct destructive lesions.

Rectal cancer induces a regulatory lymphocytic phenotype in the tumor-draining lymph nodes to promote cancer cell installation.

Tumor-draining lymph nodes (TDLNs) are critical organs, where activation of B cells and T cells is orchestrated. Effector or regulatory anti-tumor immune responses are reflected by the composition of the lymphocytic and monocytic cell population of the node. Aside from the migratory cancer cell abilities, immune cell phenotypic changes in the TDLNs may define nodal invasion by cancer. We assessed the qualitative and quantitative differences between lymphocytic phenotypes in regional TDLNs, in 20 node-negative and 20 node-positive patients (involved and uninvolved nodes) with rectal adenocarcinomas. Benign reactive nodes were also analyzed. CD8+ cells, the main source of cytotoxic T cells, were increased in all TDLNs and, even stronger, in the involved nodes. The percentage of CD4+ cells were significantly increased in negative and uninvolved nodes, while the CD4/CD8 ratio was significantly lower in involved TDLNs. CD25+ and FOXP3+ regulatory lymphocytes, however, prevailed in involved nodes, while uninvolved and negative nodes had a low presence of these regulatory cells. CD20+ B cells were also more abundant in involved nodes. PD-1+ lymphocytes were localized in the germinal centers. A significantly lower percentage of PD-1+ lymphocytes were noted in involved nodes. The development of a regulatory lymphocytic phenotype in the TDLNs appears as an important mechanism that allows cancer cell installation into the nodal environment. As negative/uninvolved TDLNs had a less severe immunosuppression, it is postulated that secreted molecules by cancer cells gradually attenuate the anti-tumor defenses of the TDLNs allowing the subsequent intra-nodal growth of cancer.

Primary ectopic Merkel cell carcinoma without skin involvement-report of a case with prolonged survival.

Merkel cell carcinoma is a rare neuroendocrine malignancy that arises from the dermis, in cases of immunocompromised, middle-aged patients or on skin exposed to sunlight. It only rarely presents in extra-cutaneous locations. We present the case of a 63-year-old female with a mass in the adipose tissue of the upper arm, without skin involvement and concurrent axillary lymph node enlargement. She was treated with wide excision and lymph node dissection; pathology led to the diagnosis of Merkel cell carcinoma, and she was subsequently submitted to adjuvant radiotherapy. No signs of recurrence are present 8 years postoperatively. Primary Merkel cell carcinoma can rarely be located in the adipose tissue without skin involvement. In cases of high suspicion, preoperative MRI scan can show the extent of the lesion, as well as lymph metastases.

P16 detection in benign, precursor epithelial lesions and carcinomas of head and neck.

BACKGROUND: Human papillomavirus (HPV) had recently been implicated in the pathogenesis of Head and Neck SCCs. The biological role of HPV in benign and pre-cancerous lesions is far less studied. p16 is a widely accepted marker to detect immonohistochemically the presence of HPV. METHODS: We evaluated, immunohistochemically, expression of p16 in 212 specimens: glottis, supraglottis, oropharynx, nasal/paranasal, with various diagnoses: hyperplasia, polyp/nodule, keratosis, papilloma, inverted papilloma, dysplasia, cancer (SCC). Analysis was completed according to location and disease. RESULTS: Hyperplasias/polyps were all negative for p16. A small percentage of papillomas was p16+ regardless of their location (12.5 %), the majority of inverted papillomas were p16+ (78.6 %) and statistically significant (p < 0.04). In carcinomas, 18/59 were p16+ (30.5 %): nasal/paranasal SCCs had a significantly higher percentage of p16+ cancer cells compared to glottis (p = 0.009), while tumours of the supraglottis/oropharynx had an intermediate score for p16+ cells (p = 0.07). Dysplasias were p16+ in 9/64 (14 %) regardless of grading (p = 0.03 compared to carcinomas). CONCLUSION: p16 was highly detected in inverted papillomas and in certain anatomic sites; however, it failed to be traced in benign lesions and only rarely encountered in dysplasias.

Endoscopic ultrasound-guided fine needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: a report of 3 cases.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is an exceedingly rare pancreatic tumor. We present the clinical, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytologic features and immunohistochemical findings performed on cell blocks of 3 SPTPs. CASES: Three females (17-32 years old) were admitted to our hospital due to unexplained episodic abdominal pain. EUS confirmed the presence of a mass in the body and tail of the pancreas (2 cases) and in the head (1 case), with distinct borders and occassional dilation of the peripheral part of the pancreatic duct. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform polyhedral cells, forming branching papillary clusters with delicate fibrovascular cores and nuclear overlapping (2 cases) and glandlike structures (1 case). Variable hyaline, myxoid stromal elements and naked capillaries were also seen. The cells had bland nuclear features, small nucleoli, nuclear grooves in some of them and focally cytoplasmic projections. Mitoses and necrosis were not observed. The immunohistochemistry on cell blocks revealed: vimentin+ (3 cases), CA19.9+ (2 cases), cytokeratin 7+ (focal, intensive, 1 case), synaptophysin+ (1 case), MUC1+ (focal, intensive, 1 case), EMA+ (diffuse weak, 1 case), a1-antitrypsin and a1-antichymotrypsin+ (focal intensive, 2 cases), progesterone+ (1 case), chromogranin-A- (3 cases) and NSE- (3 cases). CONCLUSION: Cytologic and immunohistochemical findings were strongly suggestive of SPTP. Surgical resection confirmed the diagnosis in all cases. EUS-FNA cytology features and immunohistochemistry provide the diagnosis of SPTP with accuracy.

Fine needle aspiration cytology diagnosis of primary renal lymphoma involving the pleura: a case report.

BACKGROUND: Primary renal lymphoma is a rare disease (< 1% of kidney lesions). We present a case of renal large B-cell type non-Hodgkin's lymphoma (NHL) with right sided pleural involvement. CASE: A 70-year-old man was admitted with persistent, painless, macroscopic hematuria for 1 month. Ultrasound examination, abdominal computed tomography and magnetic resonance imaging techniques revealed a large tumor in the right kidney extending in the perirenal area. The patient underwent a radical nephrectomy for suggested renal cell carcinoma. He developed thoracic pain and pleural effusion in the 10 days after surgery. The pleural fluid was cytologically processed using conventional and ThinPrep (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) cytopreparatory techniques, slides were Papanicolaou and Giemsa stained, and immunocytochemistry was performed on the ThinPrep slides. The cytologic examination of the fluid specimen revealed a highly cellular smear composed of dispersed neoplastic cells of intermediate and large size. Immunocytochemically, the neoplastic cells were: CD45 (LCA) (+), CD20 (+), CK7 (-), CK20 (-), NSE (-), CD45 RO (UCHL-1) (-) and CD30 (-). On cytomorphologic and immunocytologic examination, the specimen fulfilled the criteria of a large B-cell type NHL. Histologic evaluation of the nephrectomy specimen revealed an infiltrating, diffuse large cell renal NHL, B-cell type, of immunoblastic and centroblastic morphology. This NHL was considered a renal primary because no peripheral lymphadenopathy or hepatosplenomegaly was revealed by the imaging techniques. CONCLUSION: Cytomorphologic and immunocytologic examination revealed the typical features of a renal large B-cell type NHL in a case with pleural involvement.

Expression of c-kit in common benign and malignant breast lesions.

AIMS AND BACKGROUND: c-kit (CD117) is a transmembrane tyrosine kinase that acts as a type III receptor for mast cell growth factor. In recent years, the role of c-kit in the development of preinvasive and invasive breast carcinomas has been investigated. The aim of our study was to detect c-kit expression in the entire spectrum of common benign and malignant breast lesions in correlation with a well-studied myoepithelial or stem-cell like marker (p63). METHODS AND STUDY DESIGN: We evaluated 270 cases of benign and malignant breast lesions including fibrocystic disease, fibroadenoma, sclerosing adenosis, atypical ductal hyperplasia, ductal/lobular carcinoma in situ, and ductal/lobular/mixed type carcinoma. C-kit staining was evaluated in the cytoplasm/cell membrane in epithelial and myoepithelial cells and p63 in the nuclei of myoepithelial cells. RESULTS: c-kit was highly expressed (85.3%) in benign lesions (fibrocystic disease, sclerosing adenosis, fibroadenoma), and p63 expression was 95.5% in the aforementioned lesions. c-kit distribution in preinvasive and invasive lesions was as follows: ductal/lobular carcinoma in-situ, 43%/35%; ductal/lobular carcinoma, 36%/39%; and mixed type carcinoma, 20%. c-kit was highly expressed in myofibroblast/fibroblast cells only in grade III ductal/lobular carcinomas. c-kit was totally absent in stromal cells in benign lesions and in situ carcinomas whereas expression was weak in grade I and II carcinomas. CONCLUSIONS: Combined overexpression of c-kit and p63 is indicative of benign breast lesions. In contrast, there is reduced expression of c-kit in in situ and invasive breast carcinomas, with simultaneous overexpression in the stromal cells. This suggests that c-kit may play a role in breast cancer progression.

CK19 and CD10 expression in pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound-guided fine-needle aspiration cytology.

BACKGROUND: CK19 and CD10 are useful markers in the differential diagnosis of pancreatic tumors. The authors evaluated CK19 and CD10 expression in pancreatic neuroendocrine tumors (NETs) obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Twenty-eight patients diagnosed with pancreatic NETs based on EUS-FNA cytology were studied retrospectively (2004-2007) for immunohistochemical expression of CK19 and CD10. Immunohistochemistry was performed on cell blocks for each case. The pattern of expression for CD10 (cytoplasmic or membranous) and its intensity (0-2) were noted. The staining of the stromal elements for CD10 was recorded as negative. Cytoplasmic staining in tumor cells and percentage distribution (1+ to 4+) for CK19 were regarded as positive. RESULTS: Twenty-three of 28 (82.14%) NETs showed positive cytoplasmic and/or membranous staining for CD10, and 25 of 28 (89.29%) cases were positive for CK19. CONCLUSIONS: The findings demonstrate the high expression of CD10 and CK19 in pancreatic NETs. This indicates that CD10 and CK19 cannot reliably differentiate NETs from other tumors with similar cytomorphologic features (solid pseudopapillary tumors, which frequently stain with CD10, and pancreatic adenocarcinoma, which stains with CK19).

Spiradenocylindrocarcinoma. Report of a case with a low-grade component of spiradenocarcinoma and an immunohistochemical study.

Spiradenocylindrocarcinoma is a very rare malignant cutaneous neoplasm of the folliculosebaceous-apocrine unit. We report a case of this hybrid tumor in a 42-year-old woman. The tumor consisted of 2 circumscribed nodules with areas of cylindrocarcinoma and low-grade spiradenocarcinoma. In the overlapping areas, both spiradenomatous and cylindromatous features were observed. Expansion of the tumor beyond the fibrous pseudocapsule into the adjacent tissue was present. Furthermore, tumor cells were demonstrating mild to moderate pleomorphism and an increased mitotic index. p53 and ki-67 were among the positive immunohistochemical markers. A relatively small number of tumor cells expressed estrogen receptors. The aim of this study was to investigate the nature of this rare tumor of the skin appendages.

The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors: a study by endoscopic ultrasound-guided fine-needle aspiration cytology.

BACKGROUND: The biologic behavior of pancreatic neuroendocrine tumors (NETs) is difficult to predict in the absence of metastases or invasion into adjacent organs. In this study, the authors retrospectively evaluated the cytopathology and proliferative activity in cytology specimens obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Thirty-five patients who were diagnosed with pancreatic NET based on EUS-guided FNA were studied retrospectively (2002-2007). Cytopathology and proliferative activity (Ki-67) in cytology specimens were reviewed. Patients were divided into 2 groups: Group A (all patients with simultaneous, suspicious, metastatic masses [unresectable tumors]) and Group B (patients with final histopathologic diagnosis). Moreover, the patients in Group B were classified into 4 risk subgroups according to the 2004 World Health Organization (WHO) classification (Subgroups 1a, 1b, 2, and 3). RESULTS: Thirteen of 35 patients who were diagnosed with unequivocally malignant tumors were placed in Group A (unresectable tumors), and 22 of 35 patients were placed in Group B. In Group A, >2% Ki-67-positive cells were present in 12 of 13 patients (92.3%). In Group B, >2% Ki-67-positive cells were present in 0 of 6 patients in WHO Subgroup 1a (0%), in 3 of 7 patients in WHO Subgroup 1b (42.86%), in 7 of 7 patients in WHO Subgroup 2 (100%), and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nuclear pleomorphism/multinucleation was observed in 8 or 13 patients (61.53%). In Group B, nuclear pleomorphism/multinucleation was observed in 4 of 7 patients in WHO Subgroup 2 (57.14%) and in 2 of 2 patients in WHO Subgroup 3 (100%). In Group A, nucleoli were present in 7 of 13 patients (53.85%); whereas, in Group B, nucleoli were present in 6 of 7 patients in WHO Subgroup 2 (85.7%) and in 2 of 2 patients in WHO Subgroup 3 (100%). None of the remaining cytologic features that were evaluated (necrosis, mitoses, spindle cells, and molding/crush artifact) were observed consistently in malignant NETs. CONCLUSIONS: The current results indicated that Ki-67 evaluation in routine EUS-FNA cytology specimens can be used as a potential prognostic marker in pancreatic NETs. Nuclear pleomorphism/multinucleation and the presence of nucleoli also are reliable for predicting malignant pancreatic NETs. Cancer (Cancer Cytopathol) 2009. (c) 2009 American Cancer Society.

Cytopathological diagnosis of metastatic pleomorphic liposarcoma in the lung: a report of a case correlated with the histopathology of the primary tumour.

Pleomorphic liposarcoma (PLS) is morphologically defined by the presence of pleomorphic lipoblasts in a background of high-grade sarcoma. Representing the rarest variant of liposarcoma, PLS frequently metastasizes, most commonly to the lungs. We present the case of a 72-year-old male patient with pulmonary metastatic PLS. The primary tumour was located in the back thoracic wall. Cytopathological confirmation of the metastasis to the lung was offered using bronchoscopical sampling methods. Bronchial brushing and washing of the visible metastatic lesion revealed pleomorphic spindle-shaped cells of high-grade sarcoma with occasional lipoblasts.

CD56 as a useful marker in the regenerative process of the histological progression of primary biliary cirrhosis.

OBJECTIVE: Owing to recent contradicting results in the study of the regenerative process after hepatic injury in primary biliary cirrhosis, we investigated the use of CD56 in tissue repair during the histological progression of primary biliary cirrhosis. METHODS: Fifty-three specimens were classified into Ludwig's stages (1-4) as follows: 14 specimens as stage 1, 23 as stage 2, 14 as stage 3, and two as stage 4. Immunohistochemical stain was performed for CD56. The cell types expressing the marker were morphologically analyzed to determine their origin. RESULTS: In normal liver biliary epithelial cells (including the epithelium of terminal bile ducts and bile ductules), hepatocytes, and intermediate cells (features between hepatocytes and biliary cells, distributed in interface between hepatic parenchyma and portal tract) were CD56. In primary biliary cirrhosis specimens, biliary epithelial cells, hepatocytes, and intermediate cells were CD56 distributed as 10 out of 14 cases as stage 1 (71.43%), 18 out of 23 as stage 2 (78.26%), nine out of 14 as stage 3 (64.28%), and two out of two as stage 4 (100%). The total positive cases were 39 of 53 (73.58%). CD56 was expressed equally in all three types of cells. CONCLUSION: These findings indicate that the consistent and uniform expression of CD56 in biliary epithelial cells, hepatocytes, and intermediate cells during hepatic injury in primary biliary cirrhosis is probably related to cellular damage and may be important in tissue regeneration. Furthermore, we cannot distinguish a specific cell type from the three above mentioned ones (biliary epithelial cells, hepatocytes, intermediate cells) as a putative stem cell in primary biliary cirrhosis.

Endoscopic ultrasound-guided fine-needle aspiration cytology of pancreatic neuroendocrine tumors: a study of 48 cases.

BACKGROUND: Neuroendocrine tumors (NETs) of the pancreas are relatively uncommon tumors. The objective of this report was to describe the cytopathologic and immunocytochemical features of NETs obtained by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). METHODS: Forty-eight patients who were diagnosed with pancreatic NETs based on EUS-guided FNA were studied retrospectively (from 2002 to 2007). Clinical data, EUS findings, cytopathologic features, and immunocytochemical stains were reviewed for this study. The final histopathologic diagnosis from each patient also was available for comparison. RESULTS: Forty-eight patients (28 men and 20 women) who ranged in age from 16 years to 86 years were selected and had the following clinical findings: solid or multiple pancreatic masses diagnosed by computed tomography or magnetic resonance imaging studies; simultaneous, suspicious, metastatic masses in the liver, mediastinum, and/or lung; hypoglycemia; multiple endocrine neoplasia type 1 syndrome; von Hippel-Lindau syndrome; and primary NET of the small bowel. EUS findings revealed solid or multiple masses in the pancreatic head/uncinate, or in the pancreatic body/tail, or simultaneously in the pancreatic head/uncinate and body/tail. Cytologically, 40 patients were diagnosed with NETs (histopathogically confirmed), and 8 patients had findings that were suspicious of NETs (2 patients had false-positive results, and 6 patients had histopathologically confirmed NETs). The most helpful cytologic findings for the diagnosis of NET were a richly cellular sample with a monotonous, poorly cohesive population of small or medium-sized cells with granular chromatin (salt and pepper) and plasmacytoid morphology. Immunocytochemistry confirmed the neuroendocrine origin of tumors in 40 patients (material for immunocytochemistry was inadequate in 8 patients). CONCLUSIONS: The current results indicated that EUS-guided FNA is a useful method for the diagnosis of pancreatic NETs. Cytopathologic examination in coordination with immunocytochemistry can provide an accurate diagnosis in most patients.

Endoscopic ultrasound-guided fine needle aspiration biopsy in the diagnosis of gastrointestinal stromal tumors of the stomach. A study of 17 cases.

AIM: The gastrointestinal stromal tumor (GIST) is an uncommon tumor usually diagnosed by endoscopic biopsy or surgical resection. We evaluated the efficacy and accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) biopsy in the diagnosis of GIST. METHOD: Seventeen patients with gastric GIST diagnosed by EUS-guided FNA were included in this study (from 2005 to 2007). A single endosonographer performed all procedures. An attending cytopathologist was present on site to assess specimen adequacy. All tumors were reviewed for EUS, cytomorphologic, histologic and immunohistochemical features. RESULTS: Eleven patients (64.7%) were male and six (35.5%) were female, with a median age of 60.7 years. The clinical indication for EUS-FNA procedure in all patients was the evaluation of submucosal tumor. EUS revealed a solid hypoechoic tumor in all cases with the largest diameter being from 9.5 mm to 70 mm (median diameter 31.9 mm). Cytologic specimen was adequate upon on-site evaluation in all cases, with an average of two passes performed. Spindle cells were present in the cytologic material in all cases and epithelial cells in two cases. Nuclear irregularities and mitoses were not observed. Immunohistochemical (IHC) stain in cell blocks confirmed the c-kit and CD34 positivity in all cases. There were no false negative or false positive findings. CONCLUSIONS: This is the first study of EUS-guided FNA procedure in the diagnosis of gastric GIST in Greece. We demonstrated that EUS-FNA provides accurate diagnosis of GIST in combination with IHC reactivity for c-kit, performed in adequate cytology specimens obtained by FNA.