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Objective: To evaluate the utility of claudin‐4 as a pan‐carcinoma marker in cell‐blocks of effusion specimens and compare results with Ber‐Ep4 staining. Methods: Effusion cell‐blocks (n = 284) were stained for claudin‐4 and results compared with Ber‐Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas. Results: All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin‐4. Claudin‐4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin‐4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin‐4 outperformed Ber‐Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin‐4 compared with Ber‐Ep4, respectively. Only two cases were claudin‐4−/Ber‐Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin‐4 (131/137; 95.6%) than Ber‐Ep4 (117/137; 86.2%). Claudin‐4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin‐4 and Ber‐Ep4. Conclusions: Claudin‐4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber‐Ep4. The utility of claudin‐4 as a pan‐carcinoma marker in cell blocks of effusion specimens was investigated and compared with Ber‐Ep4 staining results. Claudin‐4 was found to be superior to Ber‐Ep4, staining 95.6% (131/137) metastatic adenocarcinomas, 1.6% (1/63) mesotheliomas and no reactive cases (0/49). [ABSTRACT FROM AUTHOR]

The diagnosis of bone lesions is a fundamental part of the study of skeletal remains, both in the archeological and forensic context. On the one side, the literature proved the relevance of radiography for the detection of bone lesions; on the other side, the careful macroscopic observation of the morphology of bone lesions is often underestimated. For this study, we examined and performed plain radiography on 14 skeletons of the CAL Milano Cemetery Skeletal Collection diagnosed with rheumatoid arthritis, diabetes, multiple myeloma, metastatic cancer, and osteomalacia to compare the macroscopic morphology and radiographic visualization of bone lesions. At least 200 osteolytic lesions and 65 areas of proliferative bone reaction (either spongiosclerotic or periosteal) were studied. We realized "comparative sets" of macroscopic pictures and radiographic imaging of the same skeletal elements to allow comparisons of detection and recognition of bone lesions. As a result, while trabecular lesions may be lost through naked eye observation, many lesions can also be unperceived on radiographs due to contrast, including periosteal reactions, osteolytic lesions, and spongiosclerosis. The aim of this research was to investigate the strengths and pitfalls of digital radiography and macroscopic analysis and to demonstrate the synergy of a complementary approach between the two methods for lesion analysis in dry bone. [ABSTRACT FROM AUTHOR]

The purpose of this article was to report the treatment effect of image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site. The patient was a 75-year-old male. A diagnostic biopsy showed metastatic squamous cell carcinoma and the tumour size was 7.5 × 6.5 × 11.5 cm3 before treatment (N3; AJCC 7th). After external beam radiotherapy with a dose of 60 Gy in 30 fractions, the residual tumour (6.2 × 4.7 × 6.0 cm3) was treated with image-guided high-dose-rate interstitial brachytherapy boost under ultrasound guidance. The brachytherapy dose was 16 Gy in four fractions of 4 Gy each. Removal of the huge metastatic tumour was securely achieved by high dose rate interstitial brachytherapy guided with ultrasound scanning. The refractory tumour in the patients healed uneventfully after image-guided high-dose-rate interstitial brachytherapy without recurrence during the 24 months of follow-up. The image-guided high-dose-rate interstitial brachytherapy boost may be a proposed treatment strategy for metastatic carcinoma of cervical lymph nodes from an unknown primary site with radical radiotherapy, especially for huge residual tumour. [ABSTRACT FROM AUTHOR]

Manual detection and characterization of liver cancer using computed tomography (CT) scan images is a challenging task. In this paper, we have presented an automatic approach that integrates the adaptive thresholding and spatial fuzzy clustering approach for detection of cancer region in CT scan images of liver. The algorithm was tested in a series of 123 real-time images collected from the different subjects at Institute of Medical Science and SUM Hospital, India. Initially the liver was separated from other parts of the body with adaptive thresholding and then the cancer affected lesions from liver was segmented with spatial fuzzy clustering. The informative features were extracted from segmented cancerous region and were classified into two types of liver cancers i.e., hepatocellular carcinoma (HCC) and metastatic carcinoma (MET) using multilayer perceptron (MLP) and C4.5 decision tree classifiers. The performance of the classifiers was evaluated using 10-fold cross validation process in terms of sensitivity, specificity, accuracy and dice similarity coefficient. The method was effectively detected the lesion with accuracy of 89.15% in MLP classifier and of 95.02% in C4.5 classifier. This results proves that the spatial fuzzy c-means (SFCM) based segmentation with C4.5 decision tree classifier is an effective approach for automatic recognition of the liver cancer. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this article is to provide additional documentation of bone metastases to help anthropologists recognize the condition and potentially suggest the diagnosis of bladder carcinoma in differential diagnosis. Materials and methods Thirteen individuals clinically diagnosed with bladder carcinoma from the 20th century Milano Cemetery Skeletal Collection were macroscopically studied to document bone metastases in bladder cancer. Results Bone metastases were found through macroscopic observation in three individuals or 23% of the study sample. Metastases were mostly of a mixed nature (45%), although both osteoblastic (13%) and osteolytic (9%) also occurred. In particular, mixed and osteoblastic metastases exhibited different distribution patterns, even when affecting the same bones. The vertebrae (24.7%), skull (12.9%), ribs (11.7%), proximal humeri (7.8%), pelvis (5.2%), proximal femora (2.6%), sacrum (1.3%) and sternum (1.3%) were the most commonly affected. Osteolytic lesions included coalescing superficial pits or lesions perforating the bone cortex. Proliferative lesions manifested as spongiosclerosis or periosteal new bone. Mixed metastases were osteolytic lesions exposing a thickened trabecular bone or coalescent porosity with reactive new bone. Conclusions Bladder carcinoma metastases were mostly mixed, exhibiting periosteal reactions, perforations of bone cortex, spongiosclerosis and coalescing porosity. Significance Bladder carcinoma is rarely considered in the differential diagnosis of the primary organ. This study reports the macroscopic aspect of bone metastases in bladder carcinoma and may help anthropologists diagnose the condition in skeletons. Limitations Absence of evidence is not evidence of absence; some lesions may have been hidden from macroscopic observation and therefore missed. Further research Radiographic analysis and comparison with other neoplasms should provide additional details for the diagnosis of bladder cancer bone metastases. [ABSTRACT FROM AUTHOR]

Objectives: It is challenging to separate peritumoral fibrosis from fibrosis due to chronic liver disease in mass-directed liver biopsies. We evaluated the distance that peritumoral fibrosis extends from metastatic colorectal adenocarcinoma in liver.Methods: Peritumoral and distant uninvolved liver trichrome stains from 25 cases were analyzed using digital image analysis. Fibrosis was quantitated at concentric intervals from each tumor and in uninvolved liver.Results: There was a 3.9 fold (range 0.9-18.6) median increase in fibrosis in the first 0.5 mm of peritumoral liver compared to distant liver. Fibrosis levels returned to baseline at median 2.5 mm (interquartile range 1.5-5.0 mm) from tumor.Conclusions: Fibrosis is markedly increased in peritumoral liver. Fibrosis levels returned to baseline by 5 mm from tumor in approximately 75% of cases. Pathologists should be cautious of fibrosis in mass-directed liver biopsies without at least 5 mm of liver tissue distal to the mass. [ABSTRACT FROM AUTHOR]

Most uterine cervix adenocarcinomas are primary tumors. Here, we report a case of pancreatic cancer that metastasized to the uterine cervix. The patient was a 77-year-old Jehovah's Witness whose pancreatic cancer had been diagnosed 10 years previously. As she had refused blood transfusion on religious grounds, the tumor only underwent segmental excision, followed by radiofrequency wave therapy and chemotherapy. During a routine health examination 6 years after her pancreatic tumor resection, a tumor in the left lower lobe of her lung was found, and then removed. Three years after the lung surgery, her serum CA19-9 increased. A detailed examination found tumors in the ascending colon and uterine cervix. She underwent chemotherapy and radiotherapy after a right hemicolectomy, endocervical biopsy, and endocervical cytology. At present, about 10 years after her initial diagnosis, she is alive with no recurrence or metastatic findings. Morphologically, well-differentiated pancreatic adenocarcinoma is similar to endocervical type adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Therefore, careful immunohistochemical examination and clear understanding of the patient's clinical information are needed in diagnosing adenocarcinoma in the uterine cervix.

Cutaneous metastasis from breast cancer has varied clinical presentations. Herein, we present the case of a middle-aged female with a large erythematous patch and an itchy bluish-red papular eruption on the left side of the breast. The patient had a history of ductal breast carcinoma at age 40. Histology from one of the red papules revealed an atrophic epidermis and emboli of carcinomatous cells in the dermal and subcutaneous blood vessels. The morphology of the tumor cells was similar to that of the primary ductal carcinoma of the breast. The diagnosis of telangiectatic metastatic breast cancer was reached. [ABSTRACT FROM AUTHOR]

Background: The supraclavicular lymph node (SCN) is a common metastatic site for malignancies of supra and infra-diaphragmatic origin and is easily accessible for small biopsy and fine needle aspiration (FNA). In this study, the utility of SCN biopsies was analyzed for diagnosis and ancillary studies., Methods: The electronic pathology archive was searched for cases of FNA of SCNs accompanied by small core biopsies (1/2016-12/2018). The patients' demographics, diagnosis, and ancillary studies were recorded., Results: Eighty-eight cases were reviewed (49 females and 39 males), with patients' ages ranging from 23 to 84 years (mean = 52.85 years). Fifty-four (61.4%) specimens were from the left SCN and thirty-four (38.6%) from the right. All FNA cases were performed by a radiologist under ultrasound guidance and rapid on-site evaltion (ROSE) was performed by a cytologist. Nineteen cases (21.6%) were benign and sixty-nine cases were malignant (78.4%). Carcinoma was the most common malignant neoplasm (52.3%) including 38.2% (13/34) of the right SCN and 61.1% (33/54) of the left SCN cases. Metastatic lung and breast adenocarcinomas (9.1% each) were the most common carcinomas overall. Lymphoma was the second most common malignancy (17.0%) including 17.6% (6/34) of the right SCN and 16.7% (9/54) of the left SCN cases. The majority of cases were accomponied by ancillary studies for diagnosis and prognostic markers. Ancillary studies included immunostains (63 cases, 71.6%), PD-L1 testing (21 cases, 23.9%), FISH testing (7 cases, 8.0%), flow cytometry (20 cases, 22.7%) and NGS studies (8 cases, 9.1%)., Conclusion: Supraclavicular lymph nodes are easily accessible and diagnostically useful sites for detection of malignancies and molecular alterations responsive to targeted or immune therapy., (© 2023 Wiley Periodicals LLC.)

A cranium of a mature male (45-55 years) from a charnel house in Hallstatt, Upper Austria (set up in the 12th century and in use until modern times) exhibits multiple perforations that were most probably caused by a malignant tumour. The lesions vary between 44 and 4 millimetres in diameter and concern nearly all parts of the cranium (frontal, parietal, and occipital bone, maxilla), hereby pertaining to all cranial layers to a different degree. Osteolytic changes accompanied by some sclerotic bone formations are indicative of an active as well as chronic process at the time of death of the individual. Differential diagnosis was carried out by macroscopic inspection, the use of conventional radiography, computed tomography and scanning electron microscopy in the secondary electron- and backscattered electron-mode. Pathology-mimicking effects, diagenetic, and taphonomic damage as causative processes can be excluded. The same applies for various infectious diseases (mycotic, bacterial, tuberculous conditions) as well as several tumorous forms (Langerhans-cell histiocytosis, bone angioma, medullary plasmocytoma). The palaeopathological and clinical diagnostical criteria used suggest a secondary carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography (CT)-guided biopsy of spine is currently a valuable diagnostic tool and effective technique for diagnosing and planning a proper therapeutic strategy for certain spinal lesions. The reported diagnostic accuracy of core biopsy ranges from 77% to 97%. Materials and Methods: We included all patients with spinal lesions suspicious of metastasis on magnetic resonance imaging, who presented between May 2012 and April 2014 and underwent CT-guided biopsy in our study. A total of thirty patients with spinal lesions were evaluated. Results: Majority presented in the seventh decade of their life (average age = 53.93; age range = 10–72 years). Male:female ratio was 1.5:1. Pain was the most common presenting symptom (100%). Lumbar spine was the most common site of lesion followed by dorsal spine. Biopsy is the gold standard in histopathological evaluation of spinal lesions. Metastatic lesion was diagnosed in 12 (40%) cases, plasmacytoma in 12 (40%) cases, non-Hodgkin's lymphoma in 2 (6.66%) cases, small round cell tumor in 1 (3.33%) case, nonspecific chronic inflammation in two patients, and necrosis with no viable cells in one patient. The most common malignancy to metastasize to spine was adenocarcinoma. The most common primary tumor of spine was plasmacytoma - multiple myeloma. Conclusion: CCT-guided biopsy is a safe procedure, and no procedure-related complication was seen in any patient. [ABSTRACT FROM AUTHOR]

Aims: Hepatic progenitor cells (HPCs) are activated in various liver diseases, but their role in the carcinomatous environment remains unknown. We aimed to identify the possible presence and topography of HPCs in liver metastases. Methods and results: We examined 14 liver resection specimens for colorectal adenocarcinoma (n = 13) and anal squamous cell carcinoma (n = 1) metastases. Immunohistochemical markers of colonic origin (keratin 20 and CDX2) and squamous cell origin (p63), HPC [keratin 19 (K19) and CD56] and stem cell (CD44) markers, and the biliary marker keratin 7 (K7), which may also highlight HPCs, were applied on routinely processed tissue sections. Double immunohistochemistry/immunofluorescence (K7/CDX2) and confocal microscopy were used on selected sections. K7‐positive, Κ19‐positive and CD56‐positive ductular structures were encountered within the metastatic tumour (tumour interior and periphery), and in the immediate peritumoral area. Hybrid structures composed of HPCs and metastatic adenocarcinoma cells were recognised and confirmed by double immunostaining (K7/CDX2). Carcinoma cells were also observed singly or in groups within the epithelium of interlobular bile ducts and/or ductules in portal tracts without evidence of carcinomatous infiltration and at a distance from the metastatic foci. Conclusions: HPCs are observed at the periphery and in the interior of liver metastatic carcinomas. Bile ductules and small interlobular bile ducts may attract carcinoma cells serving as a potential ‘metastatic niche’, in line with their recognised role as HPC niches in non‐neoplastic liver. [ABSTRACT FROM AUTHOR]

Background: While brain metastases (BM) are the most common causes of neurologic disorders in patients with known systemic malignancies, they can often be the initial manifestations of an undetected primary elsewhere. BM are major causes of morbidity and mortality in cancer patients.Aims: We describe a mixed population (data from both retrospective and prospective collection) having a BM from a solid tumor. We report the percentage distribution of the most frequent types of BM, confirming the data published in the literature. This paper may play a role in presenting the Southeast Asian reality compared with the Western countries.Setting: A tertiary-care cancer centre.Materials and Methods: Data for 4 years were retrieved from the records of the Department of Pathology of our institute. Hematolymphoid and meningeal tumors were excluded. Hematoxylin and eosin (H and E) stained slides were reviewed, and in cases with an unknown primary, immunohistochemistry (IHC) was advised. The panel of markers was chosen based on the histomorphology on H and E sections. IHC was done in cases with an unknown primary where paraffin blocks were available.Results: Lung cancer was found to be the most common primary malignancy (n = 30; 48.4%) followed by breast cancer (n = 13; 21%), colorectal cancer (n = 6; 9.6%), and skin cancer (melanoma) [n = 3; 4.8%].Conclusion: The incidence of BM from lung and breast cancer was similar to that seen in the Western studies. However, BM from colorectal cancer and melanoma show a higher and lower incidence, respectively, in comparison with the Western literature. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Etomidate is a very effective drug in severe Cushing's syndrome that is refractory to ketoconazol. Control of the serum cortisol levels in ectopic Cushing's syndrome can be obtained with infusion rates much lower than those used in anesthesia, without respiratory side effects. [ABSTRACT FROM AUTHOR]

Metastatic tumors to the breast are rare but constitute a major diagnostic dilemma. Of these, non-mammary carcinomatous metastases to the breast are particularly challenging and, without a clinical history, may be extremely difficult to distinguish from primary breast carcinoma (PBC). We specifically studied metastatic tumors of pulmonary origin, as the lung is one of the major primary sites for carcinomatous metastasis to breast. Sixteen metastatic lung tumors to the breast were identified in our archives between 1996 and 2017 including 12 non-small cell lung carcinomas (NSCLC), one large-cell neuroendocrine, one atypical carcinoid, and two small-cell carcinomas. Adenocarcinoma was the most frequent amongst the NSCLCs (11/14). We retrieved the clinical information of these cases and reviewed the pathological characteristics to provide practical tools for pathologists to aid in their identification. Even in the absence of a clinical history of lung cancer, metastatic pulmonary adenocarcinoma to the breast should be considered in at least one of the following scenarios: (1) single or multiple well-circumscribed lesions of the breast that lack an in situ component and that are accompanied by distant metastases but negative axillary lymph nodes, (2) breast tumors that are triple negative yet not high-grade, or (3) breast tumors presenting as stage 4 disease and/or having an unusually aggressive clinical course on standard breast therapy. Accurate and timely diagnosis of these tumors is mandatory because of treatment and prognostic implications. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 8 article‐registration‐date‐day 16 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_165.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> Extracellular vesicles (EV) are blebs of cellular membranes, which entrap small portions of subjacent cytosol. They are released from a variety of cells, circulate in the blood for an unknown length of time and come to rest on endothelial surfaces. They contribute to an array of physiologic pathways, the complexity of which is still being investigated. They contribute to metastatic malignant cell implants and tumor‐related angiogenesis, possibly abetted by the tissue factor that they carry. It is thought that the adherence of the EV to endothelium is dependent upon a combination of their P‐selectin glycoprotein ligand‐1 and exposed phosphatidylserine, the latter of which is normally hidden on the inner bilayer of the intact cellular membrane. This manuscript reviews what is known about EV origins, their clearance from the circulation and how they contribute to malignant cell implants upon endothelium surfaces and subsequent tumor growth. [ABSTRACT FROM AUTHOR]