Immunohistological Features Research Articles

Congenital Juvenile Granulosa Cell Tumor of the Testis in a Fetus Showing Full 69, XXY Triploidy

Testicular juvenile granulosa cell tumor (TJGCT) occurs predominantly in infancy and may be associated with sex chromosomal abnormalities. We report a fetus aborted because of cytogenetically confirmed complete XXY triploidy. External genitalia of the fetus were female, with a short and patent vagina. The tumor presented as an abdominal multicystic mass with typical histologic and immunohistological features of JGCT. It was connected with a tubular uterus-like structure. The other gonad was an inguinally localized testis that showed histologically a Sertoli cell adenoma. Malformations typical for triploidy were also present: agenesis of the corpus callosum, stenosis of the pulmonary ostium, and hypoplasia of the lungs and adrenals. To our knowledge this is the first case of TJGCT in a triploid fetus.

Tuft-shaped astrocytes in Lewy body disease

We investigated the occurrence and distribution of tuft-shaped astrocytes (TuSAs) in 60 brains from patients with Lewy body disease (LBD), which were clinically diagnosed as Parkinson's disease (PD) or dementia with Lewy bodies (DLB), and 85 brains from control subjects. TuSAs have been documented as a neuropathological hallmark of progressive supranuclear palsy (PSP). We found phosphorylated tau (p-tau)-positive and alpha-synuclein-negative TuSAs in 10 of 60 patients with LBD and 3 of 85 control cases. TuSAs were mainly located within the precentral and premotor gyri of the frontal lobe cortex. There were only few TuSAs, but the distribution pattern and morphological and immunohistological features were similar to that in PSP. Furthermore, other p-tau positive structures, including aggregates in neurons, coiled-like glial cells and threads showed a similar distribution to those in PSP; mainly in the hippocampus, striatum, subthalamic nucleus, precentral and premotor gyri, brainstem nucleus, and dentate nucleus. In these cases, however, neuronal loss and gliosis were not seen in the regions involved in PSP, such as the subthalamic nucleus, pallidum, inferior olivary, cerebellar dentate nuclei, and periaqueductal gray matter. Clinical features were indistinguishable between the LBD with and without TuSAs. The appearance of TuSAs was not related to the frequency of Lewy bodies, neurofibrillary tangles, and senile plaques, but was significantly more pronounced with advancing age in both LBD and controls. These findings suggest that in a subgroup of elderly individual cases, especially associated with LB pathology, the glial and neuronal p-tau accumulation is increased and has a distributional pattern similar to PSP.

Interdigitating dendritic reticulum cell sarcoma: Cytologic, histologic and immunocytochemical features

Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.

Psoriatic arthritis synovial histopathology: commentary on the article by Kruithof and colleagues

The clinical features in psoriatic arthritis straddle the divide between rheumatoid arthritis on the one hand and spondyloarthropathy on the other. The paper by Kruithof and colleagues compares synovial immunohistologic features and clearly identifies psoriatic arthritis as being a member of the spondyloarthropathy family.

Immunohistopathologic evaluation of choroidal neovascular membranes following Verteporfin-photodynamic therapy

Purpose To evaluate the vascularization and proliferative activity in choroidal neovascular membranes due to age-related macular degeneration after verteporfin photodynamic therapy and submacular removal. Design Interventional case series. Methods In a retrospective review of seven patients who underwent removal of subfoveal classic choroidal neovascular membranes after treatment with photodynamic therapy 3 to 146 days earlier, membranes were stained for CD 34, CD 105, and Ki-67 and correlated with clinical pictures and fluorescein angiography. Results Fluorescein angiography performed on the day of surgery disclosed nonperfusion of the treated area 3 days after photodynamic therapy, but perfusion and leakage were seen at greater post–photodynamic therapy intervals. Membranes excised 3 days after photodynamic therapy showed CD34 and CD105 positive, mostly occluded vessels. The endothelial cells appeared damaged. Ki-67 activity was low. In membranes excised 34 to 146 days after photodynamic therapy, all vessels appeared patent and were lined by healthy endothelial cells with strong expression of CD34 and CD105. Ki-67 expression was elevated after 34 days but decreased thereafter. Conclusion Photodynamic therapy did not cause a general or complete occlusion of vessels within the choroidal neovascular membranes, as suggested by fluorescein angiography 3 days postintervention, but the endothelial cells appeared to be severely damaged. Proliferative activity within these specimens was reduced. At longer intervals after photodynamic therapy, the fibrovascular tissue seemed to recover; perfusion, hyperfluorescence, and leakage of the choroidal neovascular membranes could be detected by fluorescein angiography. The clinical appearance showed a correlation with the immunohistologic characteristics of an increased proliferative activity and patent vascularization.

Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector.

Neurogenesis has been observed in the dentate gyrus of the adult hippocampus; however, the mechanisms involved in this process are still only partly understood. In this study, we visualized the proliferation, migration, and differentiation of neuronal progenitor cells in the dentate gyrus induced by ischemic stress using improved retroviral vector. Improved retroviral vector expressing enhanced green fluorescent protein (EGFP) as a transgene was injected into the dentate gyrus of adult Mongolian gerbils. After 48 hours, transient global ischemia (TGI) was induced by bilateral common carotid artery occlusion for 5 minutes using aneurysm clips. The morphological and immunohistological features of newly-generated cells in the dentate gyrus were analyzed at various times thereafter. At 48 hours after viral injection, almost all EGFP-positive dividing cells were found in the subgranule layer (SGL). These cells proliferated and migrated to the granule cell layer (GCL), expressing the developing neuronal markers polysialic acid and doublecortin, and differentiated to neuronal nuclei-positive or calbindin-positive mature granule cells at 30 days after TGI or sham-operation. The number of GFP-positive cells in the GCL was significantly higher (P<0.05) in the ischemic animals at 30 days than in sham-operated gerbils. We saw neurogenesis in the adult dentate gyrus. Furthermore, we showed that ischemic stress promoted the proliferation and normal development of neurons at this site.

Management of gastrointestinal stromal tumors: from diagnosis to treatment.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features. They originate from gastrointestinal pacemaker cells and are characterised by over-expression of the tyrosine kinase receptor KIT. Overall 5-year survival after surgical resection of GIST is approximately 60%. However, these tumours span a wide clinical spectrum from benign to highly malignant. Prognostic factors have recently been identified for GIST and include tumour size, mitotic rate and other minor factors. At present, surgery is the standard treatment for primary resectable GIST. Benign GIST have an excellent prognosis after primary surgical treatment, with over 90% 5-year survival. While recurrent or malignant GIST, which are resistant to radiotherapy and chemotherapy, had until recently an extremely poor prognosis even after surgical resection, with median survival of 12 months. The development of a tyrosine kinase inhibitor has changed the management of unresectable malignant cases. This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST. This paper reviews the literature and our experience of GIST, including: diagnosis, pathology, treatment and prognosis.

Management of gastrointestinal stromal tumors: from diagnosis to treatment.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features. They originate from gastrointestinal pacemaker cells and are characterised by over-expression of the tyrosine kinase receptor KIT. Overall 5-year survival after surgical resection of GIST is approximately 60%. However, these tumours span a wide clinical spectrum from benign to highly malignant. Prognostic factors have recently been identified for GIST and include tumour size, mitotic rate and other minor factors. At present, surgery is the standard treatment for primary resectable GIST. Benign GIST have an excellent prognosis after primary surgical treatment, with over 90% 5-year survival. While recurrent or malignant GIST, which are resistant to radiotherapy and chemotherapy, had until recently an extremely poor prognosis even after surgical resection, with median survival of 12 months. The development of a tyrosine kinase inhibitor has changed the management of unresectable malignant cases. This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST. This paper reviews the literature and our experience of GIST, including: diagnosis, pathology, treatment and prognosis.

Bullous pemphigoid: using animal models to study the immunopathology.

Bullous pemphigoid was first described by Lever in 1953 as a subepidermal blistering disease. Its immunohistological features include dermal-epidermal junction separation, an inflammatory cell infiltrate in the upper dermis, and basement membrane zone-bound autoantibodies. These autoantibodies show a linear staining at the dermal-epidermal junction, activate complement, and recognize two major hemidesmosomal antigens, BP230 (BPAG1) and BP180 (BPAG2 or type XVII collagen). An IgG passive transfer mouse model of BP was developed by administering rabbit antimurine BP180 antibodies to neonatal mice. This model recapitulates the key features of human bullous pemphigus. Using this in vivo model system, several key cellular and molecular events leading to the bullous pemphigus disease phenotype were identified, including IgG binding, complement activation, mast cell degranulation, and neutrophil infiltration and activation. Proteinases and reactive oxygen species released by neutrophils work together to damage the basement membrane zone, causing dermal-epidermal junction separation. Recent experimental data from human bullous pemphigus studies suggest that human bullous pemphigus and its mouse IgG passive transfer model counterpart may well share not only common immunohistological features but also pathological mechanisms underlying the development of this antibody-mediated disease.

Tissue maturation during the growth of juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma involves a specific age group and changes from vascular tissue to fibrous tissue. The goal of this study was to investigate the correlation among tumor extension, the histologic characteristics of the tumor, and the patient's age. We performed a prospective study of 43 male patients with untreated juvenile nasopharyngeal angiofibroma (average age, 15.42 years). We correlated the patient's age with the extension of the tumor (analyzing the computed tomographic scan) and the immunohistologic characteristics of the tumor (morphological and morphometric analysis of the central portion of the tumor, the sphenopalatine foramen region). We observed that the larger the tumor, the smaller the number of vessels and cells, but the larger the fibrous component and the higher the grade of maturation of the tissue. The patient's age was not correlated with tumor extension or the histologic characteristics of the tumor. However, the grade of maturation of the tissue in the region of the sphenopalatine foramen was higher in larger tumors.

Dynamics and histological observation of first follicular wave in Japanese black cows.

To determine the turnover of the first follicular wave in Japanese black cows and quantitative immunohistological characteristics of the previously in vivo identified dominant follicle (DF) and largest subordinate follicle (SF) derived from ovariectomy on Day 7 (3 cows) and Day 10 (3 cows) (Day 0=estrus). Six cases of first follicular wave in cows were observed twice daily by ultrasound scanning. The number of follicles, diameter of DF and SF, and prevalence of apoptotic granulosa cells (GC) and theca cells (TC) were studied by TUNEL methods. At follicular wave emergence, 13.5 +/- 9.5 Class I (2-5 mm in diameter follicles) were found 12 hr after ovulation, and increased its number until Day 1 pm. Future DF and SF observed retrospectively were 4.9 +/- 0.8 mm and 4.9 +/- 0.9 mm at wave emergence. Deviation of DF and SF occurred on Day 3 pm with mean diameters of 8.9 +/- 1.3 mm and 6.8 +/- 0.9 mm, respectively. DF developed until Day 8 am with a maximum diameter of 14.4 +/- 1.8 mm (n=3) and then regressed. The follicular wall of the DF had a characteristic image of a healthy follicle on Day 7 and slightly atretic DF on Day 10, whereas SF showed heavy atresia on both Day 7 and Day 10 under HE staining. In the prevalence of apoptotic cells, DF were 4.4 +/- 1.0% and 17.9 +/- 4.9% on Day 7 and on Day 10 in GC, respectively, and 2.4 +/- 0.7% and 8.0 +/- 1.4% on Day 7 and on Day 10 in TC, respectively. These results showed that, 1) the first follicular wave in cows is characterized by 24 hr recruitment of small follicles and a gradual divergence of growth rates in future DF and SF, and 2) early regression of DF on Day 10 was preceded by severe apoptosis.

Urgent inferior vena cava replacement with an autologous pericardium tube graft

Urgent inferior vena cava replacement with an autologous pericardium tube graft

Experimental acute glomerulonephritis induced in the rabbit with a specific streptococcal antigen.

FITC-labelled IgG obtained from patients convalescing from acute poststreptococcal glomerulonephritis (APSGN) stains glomeruli of patients with early APSGN. We previously reported a streptococcal antigen (preabsorbing antigen (PA-Ag)) that preabsorbed the stain out of sera from the convalescent patients and thus prevented glomerular staining. To confirm the nephritogenicity of PA-Ag, we administered up to 40 mg of this antigen to rabbits for 8 days and observed them for up to 9 weeks. Immunohistological analysis showed diffuse and global glomerular staining for C3 without notable staining for gamma-globulin. Light microscopic examinations revealed slight to moderate proliferative glomerulonephritis with exudative change. Control rabbits, which received similar doses of bovine serum albumin, did not show significant staining for C3. A transient and significant decrease in CH50 was observed from weeks 3 to 7 (9.7 +/- 0.3 U/ml at week 3; normal range 12.9 +/- 0.6 U/ml). This experimental model showed a resemblance to immunological and immunohistological features of APSGN in humans. Although the precise mechanisms are yet to be determined, complement activation by PA-Ag seems to hold a key position in this model and in the human disease.

Immunohistological study of the depressed cutaneous DTH response in sheep naturally infected with an ovine lentivirus (Maedi-Visna virus).

The gross and immunohistological characteristics of the purified protein derivative (PPD)-induced cutaneous DTH reaction were studied in a group of sheep naturally infected with Maedi-Visna virus (MVV), and compared with reactions obtained in a matched control group. There was a marked, but variable, depression in the DTH lesion in the MVV group associated with a decreased density of polymorphonuclear neutrophils (PMN) and CD4+ cells in the early reaction. There were no significant differences in the densities of CD8+, gamma/delta T cells, macrophages, B cells and MHC class H-expressing cells. This work indicates that there is a significant alteration in the initial trafficking of PMN and CD4+ cells into a DTH response area in sheep infected with MVV.

Disruption of the suprabasal keratin network by mutation M150T in the helix initiation motif of keratin 10 does not affect cornified cell envelope formation in human epidermis.

Keratin 10 (K10) is known to be tightly bound to the cornified cell envelope (CCE) and this binding is thought to play an important role in enhancing the structural integrity of the cornified cells. Bullous congenital ichthyosiform erythroderma (BCIE) is a genetic disorder of keratinization caused by gene mutations in the conserved sequences of keratin 1 (K1) or K10, which leads to abnormal suprabasal keratin network assembly. In BCIE patients' skin, the keratin network abnormalities make the upper spinous and granular keratinocytes fragile and result in blister formation. However, the exact pathomechanism of the hyperkeratosis seen in BCIE is still unknown. The involvement of the CCE in the pathomechanism of hyperkeratosis in BCIE is controversial. Abnormal CCE assembly may cause hyperkeratosis as reported in cases of lamellar ichthyosis. Binding of K10 to CCE is thought to be a vital connection between the suprabasal keratin filament network and CCE. We hypothesize that abnormal suprabasal keratin assembly caused by either K1 or K10 mutations can disrupt CCE formation, resulting in the hyperkeratosis observed in BCIE. To clarify whether K10 and keratin network defects affect CCE formation in vivo, the ultrastructural and immunohistological features of CCE were studied in the epidermis of two Japanese BCIE patients from two independent families carrying an identical missense mutation M150T in the helix initiation motif of K10. Ultrastructurally, a 15-nm-thick, dense, normal-appearing CCE was formed at the cell periphery of the keratinized epidermal cells. Light and electron microscopic immunolabeling revealed that the major CCE precursor proteins, involucrin and loricrin, were normally distributed and restricted to CCE of the epidermis. Immunofluorescent labeling showed that epidermal TGases, TGase 1, TGase 2 and TGase 3, were expressed normally in the epidermis. These findings suggest that a normal CCE is formed during the process of human epidermal keratinization, even if the suprabasal keratin filament network is disrupted as with this particular K10 mutation, M150T in BCIE.

Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation

Background: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. Objective: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. Methods: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. Results: First, the density of CD8+ cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 ± 8.4 (M ± SEM) per mm2 to 39.9 ± 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-γ, IL-12, and TGF-β in NP was significantly greater than in control NM tissues. The density of IL-4+ and IL-5+ cells in NP tissues significantly decreased after budesonide treatment from 40 ± 12 to 17.8 ± 8 and from 19.3 ± 11 to 10.4 ± 7, respectively. In contrast, the density of IFN-γ+ and IL-12+ cells remained unchanged. In addition, we found that the density of TGF-β+ cells significantly increased after intranasal budesonide from 18 ± 5 to 41 ± 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. Conclusions: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-β. (J Allergy Clin Immunol 2003;112:37-44.)

A case of rectal GIST: findings of MR-spiral CT imaging and transrectal ultrasound guided biopsy

Gastrointestinal stromal tumor (GISTs) are uncommon mesenchimal tumor of the gastrointestinal tract, that are defined with histological and immunohistological features; they develop more often in the stomach and in the small bowel, but are rarely seen in the rectum. We analyze a case of rectal tumor evaluated by magnetic resonance (MR) imaging and spiral computed tomography (CT). Patient underwent transrectal ultrasound guided biopsy that permitted the histological and immunohystochemical diagnosis of GIST. The aim of this study is to describe the MR and CT findings of this case of an uncommon rectal tumor and to review the international literature about GIST.

Benign intramural schwannoma of the oesophagus: a diagnostic pitfall

A 33-year-old man underwent resection of a benign intramural schwannoma of the oesophagus. Similar clinicopathological and immunohistological features prompted a review of an earlier case initially diagnosed as a S-100 negative leiomyosarcoma. This stained positive using a new S-100 immunohistochemical antibody (Dako, Trappes, France). The frequency of these extremely rare tumours may be higher than initially thought. Pitfalls for the surgeon are highlighted and attention is brought to a recent consensus.

Immunohistochemical classification of the localization of laminin in the thickened bronchial epithelial basement membrane of deceased bronchial asthma patients

To ascertain histological changes in the basal lamina of the bronchial epithelial basement membrane in patients with severe bronchial asthma, an immunohistochemical study was conducted in 43 patients who died of bronchial asthma. Antibodies against laminin, a component of the lamina lucida, were utilized. The results revealed various patterns for immunoreactivity to laminin in the thickened basement membrane layer. We were able to classify these reactivities into four patterns. In Pattern A, laminin reactions branched vertically in relation to the thickened basement membrane layer. In Pattern B, laminin reactions formed lines along the lower margin of the thickened basement membrane layer. In Pattern C, laminin reactions formed lines along the upper margin of the thickened basement membrane layer. Finally, in Pattern D, no laminin reactions were observed. In addition, relationships between immunohistological characteristics of laminin and findings such as epithelial cell shedding, basal cell proliferation and basement membrane layer thickening were investigated. In many Pattern A patients, epithelial cell shedding was observed, but goblet cell hyperplasia and basal cell proliferation were barely detectable. Conversely, in numerous Pattern D patients, epithelial cell shedding was barely seen, but goblet cell hyperplasia and basal cell proliferation were marked. Hence, Patterns A and D were on opposite ends of the spectrum of morphological characteristics associated with severe bronchial asthma. In Patterns B and C, laminin reactions formed lines along the lower and upper margin of the thickened basement membrane layer, respectively. However, no marked differences existed in epithelial cell shedding and basement membrane layer thickening. The present study is thus the first to clarify that laminin reactions in the thickened basement membrane layer vary, and this feature is unique to the bronchi of patients with severe bronchial asthma.

Primary pulmonary pleomorphic adenoma. An immunohistochemical study and review of the literature.

Primary pleomorphic adenoma of the lung is an uncommon condition. We present a case of primary pulmonary pleomorphic adenoma and its immunohistologic features. The presence of immunoreactivity to both anticytokeratin and antivimentin antibodies for its epithelial components is suggestive of a primary pulmonary lesion. Its high proliferation index and its immunoreactivity to tumor regulatory gene p16(INK4A) are features that, to our knowledge, have not been reported previously. They may have a role in the frequent recurrence of these tumors many years after their apparently complete excision. Detailed genetic investigation and long-term follow-up of this rare tumor will aid in the characterization of its biologic profile.