Developmental topographical disorientation: a newly discovered cognitive disorder

A variety of lesions in different cerebral regions may affect the human ability to orient in the environment, resulting in ‘topographical disorientation’. In a recent study, we documented the first case of Developmental Topographical Disorientation (DTD), in a person with a life-long inability to orient despite otherwise well-preserved cognitive functions, and in the absence of a cerebral injury/malformation or other neurological condition. This selective topographical disorientation was due to her inability to form a ‘cognitive map’, a mental representation of the environment, which in turn impaired her ability to orient in both familiar and unfamiliar surroundings. Here, we describe 120 new cases of DTD recruited via the internet and assessed with an online battery testing their cognitive and orientation skills. We found that people with DTD differ from matched (age, gender and education) healthy controls only in those skills confined to the orientation/navigation domain, among which the ability to form a cognitive map was the most significant factor that distinguished a person affected by DTD from control subjects.     

Podoplanin: a novel diagnostic immunohistochemical marker

Podoplanin is a transmembrane mucoprotein recognized by the recently commercially available D2-40 monoclonal antibody. Recent investigations have shown that podoplanin is selectively expressed in lymphatic endothelium as well as lymphangiomas, Kaposi sarcomas, and in a subset of angiosarcomas with probable lymphatic differentiation. Podoplanin has also been shown to be strongly expressed in seminomas, epithelioid mesotheliomas, and hemangioblastomas, and immunostaining for this marker can assist in the diagnosis of these tumors. This article reviews the current information on the applications of podoplanin immunostaining in surgical pathology.     

Sclerosing perineurioma: a clinicopathological study of five cases and diagnostic utility of immunohistochemical staining for GLUT1

We reviewed five cases of sclerosing perineurial tumor of the hand. Four patients were male and one was female with ages ranging from 11 years to 49 years (mean 26 years). The predominant reason for consultation at the outpatient clinic was a slowly growing painless mass. The sites of involvement were the thumb in two cases, and the ring finger, middle finger and palm in one case each. The lesions were hard and firm, well-circumscribed white masses with a fibrous consistency ranging from 1.2 cm to 4.0 cm (mean 2.5 cm) in maximum dimension. Microscopically, all the tumors were composed of thick collagen and variable numbers of small, epithelioid cells exhibiting corded, trabecular and whorled growth patterns. Electron microscopy showed long cytoplasmic processes with a discontinuous basal lamina and occasional pinocytotic vesicles in the tumor cells. Immunohistochemically, most of the tumor cells were positive for epithelial membrane antigen, vimentin, collagen type IV and CD10, but not for S-100 protein, CD34, desmin and cytokeratin. We also observed that the tumor cells were positive for the human erythrocyte glucose transporter (GLUT1) antigen, suggesting that GLUT1 may be a useful marker for the identification of sclerosing perineurioma.     

Discovered on gastrointestinal stromal tumour 1 (DOG1): a useful immunohistochemical marker for diagnosing chondroblastoma

Akpalo H, Lange C & Zustin J
(2012) Histopathology  60, 1099–1106 Discovered on gastrointestinal stromal tumour 1 (DOG1): a useful immunohistochemical marker for diagnosing chondroblastoma Aims: Cellular areas of chondroblastoma are composed of polygonal chondroblasts with indented nuclei and scattered osteoclast‐type multinucleated cells. To learn more about the phenotype of chondroblasts, we investigated the expression of several established immunohistochemical markers in chondroblastomas. Methods and results: Nine chondroblastomas were analysed using immunohistochemical antibodies [CD34, α‐smooth muscle actin (α‐SMA), DOG1, CD117, AE1/AE3 and CD163]. Ten chondromyxoid fibromas, seven giant cell tumours of bone and four foetal proximal femurs were also analysed. The cellular areas of each chondroblastoma contained nests of DOG1⁺αSMA⁺ CD117^? CD34^? chondroblasts, a phenotype that was not detected in chondromyxoid fibroma cases or in giant cell tumours. Although AE1/AE3 was expressed in all chondroblastomas, the staining intensity and proportion of the positive cells varied widely. Intra‐lesional CD163⁺ macrophages were detected in all cases of chondroblastoma, chondromyxoid fibroma and giant cell tumours. Conclusions: Our results demonstrated nests of membranous DOG1⁺ chondroblasts located within cellular portions of chondroblastoma containing diffuse heterogeneous infiltrates of mostly DOG1^? chondroblasts, CD163⁺ macrophages and multinucleated osteoclastic giant cells. Thus, chondroblastoma can be added to the tumours that are usually positive for DOG1, alongside gastrointestinal stromal tumour (GIST), rare solid‐pseudopapillary neoplasms of the pancreas and exceptional mesenchymal tumours including uterine type retroperitoneal leiomyoma, peritoneal leiomyomatosis and synovial sarcoma.     

Synaptophysin: an immunohistochemical marker for animal dysautonomias

Equine and feline dysautonomias are characterized histopathologically by degenerating neurons with chromatolysis, pyknotic and sometimes eccentric nuclei, and loss of Nissl substance in the peripheral autonomic ganglia. Because it may be difficult to distinguish pathological from post-mortem changes in affected ganglia by histopathological examination, synaptophysin was evaluated as an immunohistochemical marker. Degenerating neurons showed strong intracytoplasmic labelling indicating abnormal accumulation of synaptophysin. It was concluded that synaptophysin immunohistochemistry is a helpful tool for detecting degenerating neurons in equine (grass sickness) and feline (Key-Gaskell syndrome) dysautonomias.     

NKX3.1 a useful marker for mesenchymal chondrosarcoma: An immunohistochemical study

IntroductionMesenchymal chondrosarcoma is a rare subtype of chondrosarcoma. The tumor has a characteristic bimorphic pattern with areas of poorly differentiated small round cell component and interspersed islands of well differentiated hyaline cartilage. Histological diagnosis of mesenchymal chondrosarcoma is very challenging especially in small biopsies when tumor presents with little cartilaginous component. In such cases, it is very difficult to distinguish mesenchymal chondrosarcoma from other round blue cell tumors like Ewing's sarcoma, rhabdomyosarcoma, small cell osteosarcoma and desmoplastic round blue cell tumor. Immunohistochemically, mesenchymal chondrosarcoma stains positive for NKX2.2, CD99, S100 and SOX9. This immunoprofile is non-specific and overlaps with other round blue cell tumors. Till recently, there was no reliable immunohistochemical marker to differentiate mesenchymal chondrosarcoma from other round blue cell tumors.NKX3.1, though widely used as a diagnostic biomarker for prostatic adenocarcinoma, has been recently proposed by Yoshida et al. (2020) as a unique marker of mesenchymal chondrosarcoma and EWSR1-NFATC2 sarcoma.ObjectiveThe aim of our study was to further explore utility of NKX3.1 as a diagnostic marker of mesenchymal chondrosarcoma.Material & methodsWe applied NKX3.1 immunohistochemistry to 21 cases of mesenchymal chondrosarcoma and 32 cases of other round blue cell tumors.Results14 out of 21 cases (66.7%) of mesenchymal chondrosarcoma stained positive for NKX3.1 with nuclear expression in small round component. Cartilaginous component was predominantly negative. All other round blue cell tumors showed negative results.ConclusionBased on our study results we suggest that NKX3.1 is a useful immunohistochemical marker in differentiating mesenchymal chondrosarcoma from its histological mimics.     

Morphological evidence for newly discovered double projection spinal neurons

A novel population of spinal neurons is shown to terminate in two nuclei: the lateral cervical nucleus and the dorsal column nuclei. Nuclear yellow and Fast blue injected respectively into these nuclei are retrogradely transported to common neurons in the lumbosacral dorsal horn. The bifurcation of these neurons' axons appears to occur at the cervico-thoracic junction. These results indicate that some dorsal horn neurons transmit sensory information to two distinct nuclei. The two projections and their branching points may play a special role in neuronal communication.     

DLK is a novel immunohistochemical marker for adrenal gland tumors

Delta-like protein (DLK) is expressed in fetal and adult adrenal glands. We have investigated if this expression is maintained in adrenal gland-derived tumors. All the studied 37 cortical tumors, including five carcinomas, stained positively as well as the 13 examined pheochromocytomas. Thus, DLK is a very sensitive marker for adrenal tumors of cortical and medullary origin. Renal cell carcinomas, presenting the major differential diagnostic problem for cortical tumors, were all negative, as well as melanomas, which are similar to high portion of adrenocortical tumors that react with melan-A. However, all paragangliomas, some carcinoids, and thyroid medullary carcinomas were also positive for DLK. Therefore, this novel immunohistochemical marker seems useful for the identification of adrenocortical tumors while it has limited value for the distinction of pheochromocytomas from diagnostically related neuroendocrine tumors.     

WT1 as a complementary marker of malignant melanoma: an immunohistochemical study of whole sections

AIMS: To test the usefulness of WT1 as a diagnostic aid in melanoma diagnosis and prognostication. METHODS AND RESULTS: Benign naevi, Spitz naevi, dysplastic naevi and melanoma in situ, primary epithelioid, spindle cell and desmoplastic melanoma, and metastatic melanoma biopsy specimens were collected. Primary melanoma cases were grouped using the 2003 Tumour Node Metastasis classification. Cases were examined using haematoxylin and eosin and WT1-stained sections. The presence and pattern of WT1 expression were recorded. Benign naevi were uniformly negative with WT1. The majority of Spitz naevi expressed WT1 (83%). The dysplastic naevi/in situ group showed expression of WT1 in 35% of cases. The majority of primary epithelioid melanoma cases showed WT1 expression (88%). The prevalence of expression by each T category was similar, with T1 = 90%, T2 = 75%, T3 = 95% and T4 = 90%. All spindle cell and desmoplastic melanoma cases showed WT1 expression (100%). Ninety per cent of metastatic melanoma cases expressed WT1. CONCLUSIONS: WT1 is a useful ancillary diagnostic tool in routine melanoma diagnosis. WT1 expression in primary melanoma is unrelated to tumour depth. Its usefulness is limited by the fact that most Spitz naevi express WT1, up to one-third of dysplastic naevi can express WT1 and not all melanomas demonstrate its expression.     

Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma

Aims:  The incidence of mesothelioma is increasing in Europe, Japan and other developing countries. There is difficulty in the accurate diagnosis of mesothelioma and its differentiation from lung adenocarcinoma. Mesothelioma shows a complex immunohistochemical profile. Therefore, the use of a immunohistochemical panel that includes both positive and negative mesothelial markers has become a general rule for its accurate diagnosis. However, they are still not sufficient. The aim was to assess the diagnostic utility of caveolin-1 (Cav-1), which is expressed in endothelial cells, alveolar type I pneumocytes and mesothelial cells, as a novel positive marker of mesothelioma.
Methods and results:  An immunohistochemical study of 80 cases of epithelioid mesothelioma and 80 cases of lung adenocarcinoma was performed for the analysis of the expression of Cav-1 and other markers. Cav-1 expression with a membranous and/or cytoplasmic pattern was found in all of the epithelioid mesothelioma. Of these, 42 cases (52.5%) showed Cav-1 expression in >50% of tumour cells, 34 cases (42.5%) in 6–50% of tumour cells, and four cases (5.0%) in <5% of tumour cells. In contrast, only six cases (7.5%) of lung adenocarcinoma showed focal Cav-1 expression in the cytoplasm of the tumour cells. The sensitivity and specificity of Cav-1 expression for the differentiation of epithelioid mesothelioma from lung adenocarcinoma were 100 and 92.5%, respectively. This is comparable or even superior to that of currently available positive markers such as calretinin or D2-40.
Conclusions:  Cav-1 is a novel immunohistochemical marker for the differentiation of epithelioid mesothelioma from lung adenocarcinoma.     

GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

OBJECTIVE:

To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry.

INTRODUCTION:

Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data.

METHODS:

Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types.

RESULTS:

Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Forty-seven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression.

CONCLUSION:

Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined.     

Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues.

Myogenin belongs to a group of myogenic regulatory proteins whose expression determines commitment and differentiation of primitive mesenchymal cells into skeletal muscle. The expression of myogenin has been demonstrated to be extremely specific for rhabdomyoblastic differentiation, which makes it a useful marker in the differential diagnosis of rhabdomyosarcomas (RMS) from other malignant small round cell tumors of childhood. Commercially available antibodies capable of detecting myogenin in routinely processed formalin-fixed paraffin-embedded (FFPE) tissue are now available. In this study, we evaluated myogenin expression using the monoclonal myf-4 antibody (Novocastra Labs) on FFPE in a large number of pediatric tumors in order to define the clinical utility of this marker. A total of 119 tumors were studied. These included 48 alveolar RMS (ARMS), 20 embryonal RMS (ERMS), one spindle cell RMS, 16 Ewing's sarcomas (ES), six nephroblastomas, two ectomesenchymomas, seven precursor hematopoietic neoplasms, five olfactory neuroblastomas, three neuroblastomas, six desmoplastic small round cell tumors, and five rhabdoid tumors. Distinct nuclear staining for myogenin was noted in all 69 RMS. Notably, the number of positive tumor cells differed between the ARMS and ERMS. In ARMS, the majority of tumor cells (75 to 100%) were positive, in contrast to ERMS, in which the positivity ranged from rare + to 25% in all but three tumors. Additionally, myogenin positivity was seen in two of two ectomesenchymomas and in two nephroblastomas with myogenous differentiation. All other tumors were clearly negative. Our results indicate that staining for myogenin is an extremely reliable and specific marker for rhabdomyoblastic differentiation. It gives consistent and easily interpretable results in routinely fixed tissues.     

Saliviruses—the first knowledge about a newly discovered human picornavirus

The salivirus, first discovered in the year 2009, is a member of the large and growing family Picornaviridae. At present, the genus Salivirus contains 1 species Salivirus A and 2 genotypes, Salivirus A1 and Salivirus A2. Salivirus has been identified in humans and chimpanzees and may cause acute gastroenteritis in humans, having been detected in 0% to 8.7% of fecal samples collected from gastroenteritis in different human populations. Salivirus is ubiquitous in wastewater of human origin and river water specimens worldwide and represents a potential indicator human RNA virus for monitoring of environmental samples. This review summarizes the current knowledge on saliviruses including discovery, taxonomy, genome structure, and genetic diversity; covers all aspects of infection including epidemiology, molecular epidemiology, clinical feature, host species, environmental characteristics, and laboratory diagnosis; and gives a summary of possible future perspectives.     

尿路膀胱软组织肿瘤（Ⅰ）：肌纤维母细胞增生、良性肿瘤和具有不确定恶性潜能的肿瘤

大多数膀胱肿瘤起源于泌尿道上皮，为移行细胞（尿路上皮）癌，鳞状细胞癌、原发腺癌或小细胞癌比较少见，其余的膀胱癌更少见。然而，有几个不常见的特征性膀胱病变，可能由泌尿道上皮癌分化而来，包括良性和恶性的梭形细胞病变。此综述的第一部分描述了良性肌纤维母细胞的增生（包括炎症性肌纤维母细胞肿瘤和手术后梭形细胞结节）、良性肿瘤（包括平滑肌瘤、血管瘤、神经纤维瘤和神经鞘瘤）和具有不确定恶性潜能的肿瘤（包括副神经节瘤、颗粒细胞肿瘤和血管周上皮样细胞肿瘤），并描述了其常见的临床表现、形态学特征和免疫组化特点，帮助临床病理医师认识这些肿瘤实体。     

Syndecan-1 (CD138): an immunohistochemical marker of plasma cell tumors

The immunohistochemical detection of syndecan-1 (belonging to the cluster CD138) is a sensitive and reliable method for identifying normal and neoplastic plasma cells. It may be used in paraffin-embedded bone marrow specimens, as well as in extramedullary tumours of unknown origin. The three anaplastic tumours reported by us in the lymph node, the gingiva, and pleura were negative for other markers, but the syndecan-1 positivity elucidated their plasmocytic histogenesis.