Immunohistological Features Research Articles

Chorionic Villus Sampling and Hemangiomas

Chorionic villus sampling (CVS) is a widely used and safe method of prenatal diagnosis. In the 1990s, concerns were raised at several medical centers that there was an increased risk to the exposed fetus for the occurrence of limb deficiencies, hemangiomas, and other vascular disruption defects. The risk was greater when the procedure was performed earlier in pregnancy, such as 8 or 9 weeks of gestation. The postulated mechanisms for the fetal injury included blood loss, hypoperfusion, hypoxia, endothelial cell damage, hemorrhage, and tissue loss. The effect was most common in tissues with end arteries, such as digits, tongue, brain stem, and intestine. The associated hemangiomas were infantile hemangiomas. They were more common on the head, neck, and thorax and more often multiple in infants exposed to CVS. One postulated mechanism for the occurrence of these hemangiomas is embolization of angioblasts or endothelial cells from the placenta to the fetal skin. A question to be answered is whether the infantile hemangiomas in children exposed to CVS differ in immunohistologic characteristics from similar hemangiomas in children not exposed to CVS during pregnancy.

Müllerian Serous Cystadenoma of the Scrotum Following Orchiopexy

A 24-year-old man presented himself with a nodular lesion of about 1 cm diameter at the site of a previous orchiopexy associated with surgery for cryptorchism. Histopathology revealed the lesion to be adenomatous and confined to the scrotum. Histological and immunohistological features were not consistent neither with median raphe cysts or cutaneous adenomas nor with the intrascrotal adenomas of the rete testis, epididymis, nor with (malignant) mesotheliomas. However, the lesion did compare well with serous (papillary) cystadenomas of the testis or paratestis. These adenomas are thought to originate in remnants of the Müllerian system or of peritoneal lining altered by Müllerian metaplasia. This implies that the scrotal adenoma may have developed from an implant of such elements during orchiopexy 14 years ago. Complete excision of the lesion appears to be an adequate therapy.

Two different types of malignant fibrous histiocytomas from pet dogs

We describe 2 cases of malignant fibrous histiocytomas (MFHs) that spontaneously developed in young pet dogs. To classify these tumors, we applied a panel of antibodies (vimentin, desmin, α-SMA, and ED1) and Azan staining for collagen. The MFHs were most consistent with osteoclast-like giant and inflammatory cell types. The first case had positive staining for ED1 and vimentin, and given the osteoclast-like giant cells, calcification sites accompanying peripheral giant cell infiltrates. The latter case, the inflammatory cell type, exhibited a storiform-pleomorphic variant of neoplastic cells, including an ossifying matrix. MFHs are among the most highly aggressive tumors occurring in soft tissue sarcomas in elderly dogs; however, MFHs have been poorly studied from a diagnostic point of view. Herein, we describe the histologic and immunohistologic features of MFHs in detail, thus classifying the subtypes of these tumors.

Immunohistological features of hip synovitis in ankylosing spondylitis with advanced hip involvement

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that affects the spine and sacroiliac joints, as well as the peripheral joints [1]. Hip arthritis occurs in 30% of all AS pat...

Syndrome de Richter de type pseudohodgkinien. À propos de deux cas et revue de la littérature

We report the clinical and immunohistological features of two cases of chronic lymphocytic leukaemia (CLL) with Hodgkin's transformation. These cases occurred in a 70-year-old man with a three-year history of CLL and in a 76-year-old man with a few months history of CLL. Microscopic examination showed the presence of large tumor cells with the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (R-S) cells, in a background of otherwise typical B-CLL. The transformation of CLL into large B cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely does CLL transform into Hodgkin's lymphoma, but this diagnosis is often easy and offers few differential diagnoses. The major points of interest lie in the pathogenetic relationship between CLL and Hodgkin's disease, and in the potential clinical implications of this peculiar condition. Literature on the subject indicates that identical IgH gene rearrangements in micromanipulated R-S and CLL cells have been identified in 7/12 cases. In these patients, the R-S and CLL cells belong to the same clonal population, suggesting a progression from the underlying CLL cells. This group appears to have a poor prognosis, identical to classical Richter's syndrome. In other cases, the R-S cells were often Epstein-Barr virus (EBV) positive and did not share the clonal rearrangements identified in CLL cells, suggesting that Hodgkin's disease in these patients could represent a second malignancy, EBV-related and favored by immunosuppression, associated with a better prognosis.

Extra-gastrointestinal stromal tumor of the greater omentum: report of a case and review of the literature

BackgroundGastrointestinal stromal tumors (GISTs) represent the majority of primary non-epithelial neoplasms of the digestive tract, most frequently expressing the KIT protein detected by the immunohistochemical staining for the CD117 antigen. Extra-gastrointestinal stromal tumors (EGISTs) are neoplasms with overlapping immunohistological features, occurring in the abdomen outside the gastrointestinal tract with no connection to the gastric or intestinal wall.Case presentationWe here report the clinical, macroscopic and immunohistological features of an EGIST arising in the greater omentum of a 74-year-old man, with a discussion on the clinical behavior and the prognostic factors of such lesions and a comparison with the gastrointestinal counterpart.ConclusionThe EGISTs in the greater omentum can grow slowly in the abdomen for a long time without clinical appearance. In most cases a preoperative diagnosis is not possible, and the patient undergoes a surgical operation for the generic diagnosis of "abdominal mass". During the intervention it is important to achieve a complete removal of the mass and to examine every possible adhesion with the gastrointestinal wall. Yamamoto's criteria based on the evaluation of the mitotic rate and the MIB-1 labelling index seems to be useful in predicting the risk for recurrence or metastasis. More studies are necessary to establish the prognostic factors related to localization and size of the EGIST and to evaluate the impact of the molecular characterization as an outcome parameter related to the molecular targeted therapy. In absence of these data, an accurate follow-up is recommended.

In vivo transformation of mouse conventional CD8α+ dendritic cells leads to progressive multisystem histiocytosis

Division and proliferation of dendritic cells (DCs) have been proposed to contribute to homeostasis and to prolonged antigen presentation. Whether abnormal proliferation of dendritic cells causes Langerhans cell histiocytosis (LCH) is a highly debated topic. Transgenic expression of simian virus 40 (SV40) T antigens in mature DCs allowed their transformation in vivo while maintaining their phenotype, function, and maturation capacity. The transformed cells were differentiated splenic CD8 alpha-positive conventional dendritic cells with increased Langerin expression. Their selective transformation was correlated with higher steady-state cycling compared with CD8 alpha-negative DCs in wild-type and transgenic mice. Mice developed a DC disease involving the spleen, liver, bone marrow, thymus, and mesenteric lymph node. Surprisingly, lesions displayed key immunohistologic features of Langerhans cell histiocytosis, including expression of Langerin and absence of the abnormal mitoses observed in Langerhans cell sarcomas. Our results demonstrate that a transgenic mouse model with striking similarities to aggressive forms of multisystem histiocytosis, such as the Letterer-Siwe syndrome, can be obtained by transformation of conventional DCs. These findings suggest that conventional DCs may cause some human multisystem LCH. They can reveal shared molecular pathways for human histiocytosis between humans and mice.

Nodal marginal zone B‐cell lymphoma with prominent follicular colonization – difficulties in diagnosis: a study of 15 cases

While colonization of reactive follicles is well described in mucosa-associated lymphoid tissue lymphoma, this is not fully appreciated in nodal marginal zone B-cell lymphoma (NMZL). The aim was to address how to recognise this feature/entity and to discuss diagnostic difficulties faced by histopathologists in dealing with such lesions and their biological implications. Fifteen NMZLs with prominent follicular colonization are described, 14 of which were referrals from other hospitals. All cases had a follicular pattern and showed prominent 'follicular colonization'. In many follicles the colonization was partial, and follicles also had a reactive germinal centre component. The phenomenon of follicular colonization was highlighted by immunohistochemistry. The benign follicle centre cells expressed CD20, CD10 and Bcl-6 and were negative for Bcl-2 and MUM1. In contrast, the colonizing marginal zone lymphoma cells expressed CD20, Bcl-2 and often MUM1 and were negative for Bcl-6 and CD10. Partially colonized follicles showed a 'moth-eaten' appearance on CD10, Bcl-2, Bcl-6 and MUM1 immunohistochemistry. In none except one was the referring diagnosis NMZL. Recognizing and appreciating follicular colonization in a subset of NMZLs, appropriate use of immunohistochemistry and knowledge of immunohistological features can aid in making the correct diagnosis.

Gastrointestinal stromal tumour of the rectum: Report of a case and review of literature

Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CD117 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and non-metastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.

Clinical and Immunopathologic Alterations in Rhesus Macaques Affected with Globoid Cell Leukodystrophy

Globoid cell leukodystrophy, or Krabbe's disease, is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. Herein, we describe the clinical, neuropathological, histochemical, and immunohistological features observed in rhesus macaques affected with Krabbe's disease. Clinical signs included pronounced muscle tremors of head and limbs, difficulty ambulating, ataxia, hypermetria, proprioceptive deficits, and respiratory abnormalities. Histopathologically, all animals presented with evidence of demyelination in the peripheral and central nervous systems and accumulation of mononuclear and multinuclear globoid cells in the cerebral and cerebellar white matter associated with severe gliosis. Using immunohistochemistry and multi-label confocal microscopy, it was determined that globoid cells were CD68+, HAM56+, LN5+, CD163+, IBA-1+, and Glut-5+, suggesting that both peripheral blood-derived monocytes/macrophages and resident parenchymal microglia gave rise to globoid cells. Interestingly, many of the globoid cells and parenchymal microglia with a more ameboid morphology expressed HLA-DR, indicating immune activation. Increased expression of iNOS, TNF-alpha, and IL-1 beta were observed in the affected white matter, colocalizing with globoid cells, activated microglia, and astrocytes. Cytokine mRNA levels revealed markedly increased gene expression of CCL2 in the brain of affected macaques. CCL2-expressing cells were detected throughout the affected white matter, colocalizing with GFAP+ cells and astrocytes. Collectively, these data suggest that dysregulation of monocyte/macrophage/microglia and up-regulation of certain cytokines may contribute to the pathogenesis of Krabbe's disease.

An uncommon folliculosebaceous cystic hamartoma on the lower extremity

Folliculosebaceous cystic hamartomas (FSCH) are a recently recognized cutaneous hamartoma comprised of follicular, sebaceous and mesenchymal elements. Only nine cases have been previously reported. The authors present a case of FSCH on the lower extremity in addition to a literature review. To further characterize the clinical, histological and immunohistological features of FSCH. The clinical, histological and immunohistological features of FSCH were evaluated and the literature reviewed. This lesion uncommonly presents as exophytic papules or nodules on the leg, and most commonly presents on the central part of the face. Clinical differential diagnoses included nevus, neurofibroma and adnexal tumour. The diagnostic microscopic features of infundibular cystic structures with attached sebaceous glands and characteristic stroma were present in all lesions. Many of the stromal spindle cells were CD34-positive. The FSCH is a recently recognized hamartoma comprised of follicular, sebaceous and mesenchymal elements. Although reported only rarely, its incidence is likely much higher. In the present patient, the FSCH was located in femoral region, which is very rare.

Nasal and Nasopharyngeal Lymphoma in Cats: 50 Cases (1989–2005)

Lymphoma is the most common nasal cavity tumor in cats, yet few reports specifically address the anatomic, immunohistologic, and cytologic features of this neoplasm. Fifty cats were diagnosed with lymphoma at necropsy, via biopsy or by cytology alone. Ten cats displayed multiorgan involvement, and in 2 of these the involvement was limited to the cerebellum and frontal cortex, respectively. Of the tumors, 41 of 50 (82%) were classified as nasal lymphoma, 5 of 50 (10%) were classified as nasopharyngeal lymphoma, and 4 of 50 (8%) involved both nasal and nasopharyngeal tissue. Histologically, all were considered diffuse lymphoid neoplasms and no cats displayed features of follicular lymphoma. Of the 44 cases available for slide review by the pathologist, 40 of 44 (91%) were classified as immunoblastic lymphoma, 2 of 44 (5%) as diffuse large cell, and 1 as diffuse mixed; 1 was unclassified. Of the 45 cats for which immunohistochemical stains were available, 32 were uniformly positive for CD79a, 7 were uniformly CD3 positive, and 6 had a mixed population of CD79a and CD3 cells. Epithelioptropism was exhibited in 4 of 5 (80%) cats in which there was sufficient epithelium present for evaluation. Of those 4, 3 were B-cell and 1 was a granulated T-cell lymphoma. In the 21 cats which nasal cytology was performed, 15 were cytologically diagnosed with lymphoma; the diagnoses in the remaining five cats were inflammatory (n = 4), normal lymphoid tissue (n = 1), or nondiagnostic (n = 1). The most common biochemical abnormalities were panhyperproteinemia in 26/46 (57%) of cats and hypocholesterolemia in 11/46 (24%) of cats.

Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations

Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. Exposure to dieldrin reduced LH-induced testosterone secretion (P < 0.05) and tissue protein concentrations of LH receptor and steroid acute regulatory protein (P < 0.05). Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

Pediatric Jejunal Gastrointestinal Stromal Tumor Diagnosed by Wireless Capsule Endoscopy

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

PAX5 is a B-cell transcription factor whose expression at the protein level is reliably detected by immunohistochemistry in routine biopsies. The purpose of this study was to investigate whether PAX5 immunohistochemistry has diagnostic benefit as a B-cell marker in the work-up of undifferentiated malignant neoplasms. Twenty-five cases previously diagnosed as undifferentiated malignant neoplasms were selected. In addition, 59 hematolymphoid and 884 non-hematolymphoid malignancies were studied such that the specificity of PAX5 immunohistochemistry could be addressed. Two of the 25 (8%) undifferentiated neoplasms showed diffuse staining for PAX5, which indicated a B-cell derivation for these neoplasms that was not appreciated at the time of initial diagnosis. PAX5 staining was detected in the vast majority of hematolymphoid tumors of B-cell derivation but only in 5 of 884 (less than 1%) non-hematolymphoid tumors. Our results further show that PAX5 may be the only detectable marker of B lineage in lymphomas that lack or show equivocal CD45RB and CD20 expression. We conclude that the addition of PAX5 to a panel of immunohistologic markers used in the interrogation of undifferentiated neoplasms is of diagnostic benefit. Its expression can also facilitate the diagnosis of classical and nodular lymphocyte-predominant Hodgkin lymphoma with atypical morphologic and immunohistologic features. Lastly, we have shown that the lack of its expression at the protein level in many epithelial and mesenchymal neoplasms renders PAX5 expression an extremely specific marker of the B lineage.

Differentiation Between Pancreaticobiliary and Upper Gastrointestinal Adenocarcinomas

Metastatic adenocarcinoma of unknown primary site, eg, to lymph nodes, liver, or lung, may originate from many organs. Microscopic differentiation of adenocarcinomas from the pancreaticobiliary and upper gastrointestinal tracts may be difficult because of shared histologic and immunohistologic features. A high prevalence of cytokeratin (CK)17 expression in pancreaticobiliary adenocarcinoma was reported, and preliminary data indicate infrequent or missing expression in gastric adenocarcinoma. The prevalence of CK17 expression in gastric cardiac and esophageal adenocarcinomas has not been studied. We studied CK17 expression in tissue microarrays of 67 distal gastric, 71 gastric cardiac, and 46 esophageal adenocarcinomas and compared it with expression in 55 pancreatic, 23 extrahepatic bile duct, and 49 colorectal adenocarcinomas. CK17 expression was as follows: pancreatic, 88%; bile duct, 59%; esophageal, 30%; distal gastric, 28%; gastric cardiac, 27%; and colorectal adenocarcinoma, 6%. These differences were statistically significant for all tumor types except in comparisons of esophageal, cardiac, and distal gastric adenocarcinoma. The prevalence of CK17 expression in pancreatic and extrahepatic bile duct adenocarcinomas is substantially higher than in upper gastrointestinal tract and colorectal adenocarcinomas. However, in individual cases of adenocarcinoma of unknown primary site, CK17 results alone are insufficient to differentiate the analyzed tumor entities.

Differential development of neuronal physiological responsiveness in two human neural stem cell lines

BackgroundNeural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture.ResultsIn the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation.ConclusionThese data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters of isolation and differentiation of the cell lines, indicating that not all human NSCs are functionally equivalent.

Pulmonary rheumatoid nodules demonstrating features usually associated with rheumatoid synovial membrane

To describe the unusual immunohistological characteristics of two pulmonary rheumatoid nodules showing ectopic lymphoid follicles and the features normally associated with rheumatoid synovial membrane, and to discuss the implications of this novel observation. Two formalin-fixed wax-embedded pulmonary rheumatoid nodules were processed for immunohistology. The central structure of the pulmonary nodules was typical of that uniformly expected in a rheumatoid nodule with central necrosis surrounded by a palisade of macrophages. However, a feature not previously observed in nodules was the presence of lymphoid aggregates containing B lymphocytes and, in some cases, showing characteristic features of lymphoid follicles. The presence of B lymphocytes and the development of ectopic lymphoid follicles in rheumatoid nodules have not been described previously. It is similar to synovial membrane, and contrasts with the expected structure of subcutaneous nodules where B cells and lymphoid follicles are normally absent. These observations establish that the morphology of rheumatoid nodules can vary in different tissues. They further suggest that the inflammatory process in the nodule and synovial membrane are likely to be similar, and that the characteristics of different tissues may be an important determinant of apparent differences between inflammatory lesions in synovial membrane and extra-articular nodules in rheumatoid arthritis.

Solid serous microcystic adenoma of the pancreas

BackgroundCystic neoplasms of the pancreas are less common than solid tumors, and portend a better prognosis. They can be divided into serous and mucinous subtypes, with the former behaving less aggressively and generally considered benign. Of the serous neoplasms, serous microcystic adenoma is the most common. An extremely rare solid variant of serous microcystic adenoma lacking secretory capability has been described. Herein, we present the fourth described case of this solid variant and review the literature.Case presentationWe present a case of a 62 year-old man with a history of abdominal pain, who on CT scan was found to have a solid mass at the junction of the head and body of the pancreas. The patient was offered resection for diagnosis and treatment, and subsequently underwent distal pancreatectomy and splenectomy. Based on gross pathology, histology and immunohistochemistry, the mass was determined to be a solid serous microcystic adenoma.ConclusionSolid serous microcystic adenoma shows similar histologic and immunohistologic features to its classic cystic counterpart, but lacks any secretory functionality. It appears to behave in a benign manner, and as such, surgical resection is curative for patients with this tumor. Furthermore, until more cases of solid SMA are identified to further elucidate its natural history and improve the reliability of preoperative diagnosis, surgical resection of this solid pancreatic tumor should be considered standard therapy in order to exclude malignancy.

Painful digital Pacinian corpuscle hyperplasia following dog bite: A case report

Digital Pacinian corpuscle hyperplasia is an extremely rare, painful condition that generally follows local trauma. We report a case of painful digital Pacinian corpuscle hyperplasia of the right index finger that was preceded by a dog bite at the same site over one and a half years ago. To the best of our knowledge, this is the first instance of a Pacinian corpuscle hyperplasia following dog bite. The literature is reviewed and immunohistological features are outlined.