Neuroblastoma, ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest cells and can be conceptualized as three different maturational manifestations of a common neoplasm. To assess the validity of immunohistochemistry and DNA Ploidy in the diagnosis of neuroblastic tumor in terms of prognostication, histologic and immunohistochemical evaluation with NB-84, neuron specific enolase(NSE) and S-100 protein and flow Cytometric DNA analysis were done on 21 neuroblastomas and 19 ganglioneuromas. Thirteen of 21 neuroblastomas were undifferentiated and 8 differentiating in type. Eleven of the 19 ganglioneuromas were mature in type and 8 had immature foci. Eighty one percent of neuroblastomas were positive for NB-84, 100% for NSE and 67% for S-100 protein, respectively. All ganglioneuromas were positive for NSE and S-100 protein, in contrast, only immature foci in ganglioneuroma were positive for NB-84. B-84 reacted positively with undifferentiated and differentiating neuroblasts including neuropil but not with mature ganglion cells. In contrast, NSE reacted positively with all components of neuroblastic tumor and S-100 protein mainly with cells of Schwannian differentiation. Three of eight(37.5%) differentiating neuroblastomas were strongly positive for NB-84 in contrast with seven of thirteen(53.8%) undifferentiated tumors, reflecting that undifferentiated cells tended to be positive for NB-84 in neuroblastoma. Twenty two percent of neuroblastoma showed diploidy and 78% aneuploidy including 11% of near-diploidy. Seven of eight(87.5%) differentiating neuroblastomas in contrast with seven of ten(70%) undifferentiated tumors showed aneuploidy. By contrast, 53% of ganglioneuroma showed diploidy and 47% aneuploidy with DNA index ranged from 1.12 to 1.19. Three of nine(33.3%) mature ganglioneuromas in contrast with five of eight(62.5%) ganglioneuromas with immature foci showed aneupolidy. Differentiating neuroblastoma tended to be aneuploid and ganglioneuroma with immature foci tended to be near-diploid. In conclusion, immunohistochemistry for NB-84, NSE and S-100 protein is useful for confirming neuronal, both neuronal and Schwannian, and Schwannian differentiation, respectively. Immunohistochemistry together with flow cytometric DNA analysis would be helpful to confirm the immature foci in ganglioneuroma.
Neuroblastoma

We report three cases of neuroendocrine tumors of the lung characterized by large pleomorphic cell with frequent mitosis, which show neuroendocrine differentiation by both light microscopy or electron microscopy and iminunohistochemistry. These tumors have been categorized as large cell neuroendocrine carcinoma by Travis et al.(1991) in contrast with non-small cell lung cancer with neuroendocrine differentiation. In the latter, neuroendocrine differentiation is not evident by light microscopy and must be demonstrated by imunohistochemstry or by electron microscopy. The prognosis of large cell neuroendocrine carcinoma, together with non-small cell lung cancer with neuroendocrine differentiation, appears to be worse than cancer without neuroendocrine differentiation and intermediate between atypical carcinoid and small cell lung cancer. Larger numbers of patients will be needed to demonstrate significant differences in survival.
Lung Neoplasms

Pigmented(melanotic) schwannoma is a very rare variant of schwannoma that characteristically has massive cytoplasmic melanin. Since it was described in 1946 by Bjorneboe, about 44 cases have been reported in the English literature. It has a relatively benign clinical course, but the cases arising in the cranial nerve and sympathetic chain show aggressive behavior with malignant potential. We herein report a typical case of pigmented schwannoma with light microscopic findings. The results of immunohistochemical and electronmicroscopic study are also presented. The patient was a 30 year-old Korean male who had a mass in his posterior neck for 10 years that recently.began to induce neurologic manifestations. The tumor, which was mainly in the extramedullary intradural space of the cervical canal extending to the extradural space and soft tissues of the neck, was relatively well defined and composed of black solid tissue. Microscopic, densely pigmented spindle cells forming fascicles, nuclear palisading, whorling and polygonal cells with vacuolated or clear cytoplasm were characteristic. Immunohistochemically, the tumor cells were positive for vimentin, S-100 protein, and HMB-45. Electron microscopic study revealed that the tumor cells have interdigitating cytoplasmic processes containing varying stages of melanosomes with a very focal basal lamina and Luse body like collagen bundles.
Male ; Humans

Biliary cystadenoma of the liver is a rare multilocular cystic neoplasm of biliary origin. it occurs most often in middle aged women and rarely in children. Histogenesis of this tumor is uncertain. It may be developmental in origin arising from aberrant hamartomatous bile ducts or ectopic rests of embryonic biliary cystadenoma of the liver discovered at 8 month of intrauterine fetal life. This case supports its congenital theory.
Child ; Male ; Female ; Humans

Fifteen cases of papillary cystic tumor of the pancreas (PCTP) were studied (14 female patients, one male patient; mean age: 23.5 years). Most tumors developed in the head of the pancreas as a well circumscribed large mass. The tumor had a mean diameter of 6.7 cm(range; 2 to 15 cm). Histopathologically abundant delicate papillary fragments, monomorphic tumor cells and degenerative changes of the solid area of the tumor were characteristic. All but two cases had completely circumscribed capsules. Two cases had duodenal invasion; one of all cases had cul de sac metastasis. Compared with 12 non-aggressive tumors, the aggressive cases had larger tumor size (more than 9 cm) with a thicker capsule (more than 2 mm). In studies to investigate the prognostic index using nucleolar organizing region (NOR), proliferating cell nuclear antigen (PCNA) and flow cytometry as well as nuclear grade and mitotic index, we could not find the useful parameter to detect the malignant potential of PCTP. In the flow cytometric analysis of cellular DNA contents, two invasive cases and the only one case of the male patient among the non-aggressive group were aneuploid. In conclusion, although it is hard to predict the prognosis by microscopic findings only, those with a thick capsule and aneuploidy tend to be related to malignant potential.
Adolescent ; Adult ; Cell Division/physiology ; Cystadenoma, Papillary/*chemistry/*pathology ; Female ; Flow Cytometry ; Human ; Immunohistochemistry ; Male ; Nucleolus Organizer Region/chemistry ; Pancreatic Cyst/*chemistry/*pathology ; Pancreatic Neoplasms/*chemistry/*pathology ; Predictive Value of Tests ; Prognosis ; Proliferating Cell Nuclear Antigen/analysis ; Silver Staining ; Support, Non-U.S. Gov't

PURPOSE: This retrospective study has been undertaken to find out the clinical outcome of children with HS nephritis and its relationship with initial clinical presentation and/or renal pathologic finding. PATIENTS AND METHODS: Study population consisted of 59 children with HS nephritis who have been admitted to the Pediatric department of KyungPook University Hospital from 1987 to 1999, and biopsy was done with indications of heavy proteinuria ( > 1 g/m2/day ) lasting over 1 month, nephrotic syndrome, and persistent hematuria and/or proteinuria over 1 year. Patients were divided clinically into 3 groups ; isolated hematuria, hematuria with proteinuria and heavy proteinuria (including nephrotic syndrome). Biopsy findings were graded from I-V according to International Study of Kidney Disease in Children (ISKDC). RESULTS: Mean age of presentation was 8.1+/-3.0 years and slight male proponderance was noted ( 33 boys and 26 girls ). Histopathologic grading showed Grade I ; 2, Grade II ; 44, and Grade III ; 13 cases. Clinical outcome at the follow-up period of 1-2 years (49 cases) and 3-4 years (30 cases) showed normal urinalysis in 15 ( 30.6% ) and 18 cases ( 60.0%), persistent isolated hematuria in 20 ( 40.8% ) and 2 cases ( 6.7 % ), hematuria with proteinuria in 11 ( 22.5% ) and 8 cases ( 26.6% ), and persistent heavy proteinuria in 3 ( 6.1% ) and 2 cases ( 6.7% ) respectively. Clinical outcome according to histopathologic grading showed the frequency of normalization of urinalysis being lower in Grade III compared to grade I or II. Clinical outcome according to initial clinical presentation showed no relationship to the normalization of urinalysis at follow-up periods. However, 15-20% of children with initial heavy proteinuria showed persistent heavy proteinuria ( 3 out of 20 cases at 1-2 years, and 2 out of 10 case at 3-4 years of follow-up periods). CONCLUSION: The majority of children with HS nephritis (histopathologic grade I, II, III) improved within 3-4 years, and persistent heavy proteinuria was seen only in a few of children with initial clinical presentation of heavy proteinuria.
Biopsy ; Child* ; Female ; Follow-Up Studies ; Gyeongsangbuk-do ; Hematuria ; Humans ; Kidney Diseases ; Male ; Nephritis* ; Nephrotic Syndrome ; Proteinuria ; Retrospective Studies ; Urinalysis

OBJECTIVE: To evaluate mouse embryos development in conventional medium IVF-20 versus vero cell coculture. METHODS: Female ICR mice aged 6 to 8 weeks, were stimulated with 5IU PMSG and 48 hours later were injected 5IU of hCG, then female and male mice were mated. At 48 hour post-hCG injection, oviducts were dissected out and 2-cell embryos were flushed. The 2-cell embryos were cultured in IVF-20 media or media containing vero cell (African green monkey kidney epithelial cell lines) for 120 hours. Coculture techniques have been applied in mouse 2-cell embryos culture used vero cell lines. RESULTS: 1. After 48 hours culture, 60.7% and 55.7% of 2 cell embryos developed to 4 cell and morulae stage, respectively, in IVF-20 culture medium, but significantly less embryos developed to 4 cell (47.6%, p<0.05) and momlae (42.9%, p<0.05) in vero cell coculture. 2. After 72 hours culture, 51.6% of 2 cell embryos developed to blastocyst and expanded blastocyst in IVF-20 culture medium, but significantly less embryos developed to blastocyst and expanded blastocyst (25.9%, p<0.01) in vero cell coculture. 3. After 96 hours culture, 37.7% and 32.6% of 2 cell embryos similar developed to expanded blastocyst and hatching in IVF-20 culture medium and vero cell coculture, respectively. 4. After 120 hours culture, 36.9% and 37.4% of 2 cell embryos similar developed to expanded blastocyst and hatching in IVF-20 culture medium and vero cell coculture, respectively. CONCLUSION: There was no difference of embryo development rates between the two culture groups. IVF-20 medium alone gives a benefit to the viability of an embryo compared with a vero cell coculture.
Animals ; Blastocyst ; Cercopithecus aethiops ; Coculture Techniques* ; Embryonic Development ; Embryonic Structures* ; Epithelial Cells ; Female ; Humans ; Kidney ; Male ; Mice* ; Mice, Inbred ICR ; Morula ; Oviducts ; Pregnancy ; Vero Cells*

Background: Patients with stable psoriasis showing clearear-clear response can consider extending the dosing interval of biologics. However, few studies have reported the treatment outcomes following irregular dosing intervals of biologics in patients with psoriasis. Objective: We compared treatment outcomes after regular and irregular dosing intervals of biologics in patients with psoriasis. Methods: This single-center, retrospective observational study included patients who received biologics for treatment of plaque psoriasis between January 1, 2014 and December 31, 2019. We compared patient demographics, clinical characteristics, biologics administered, and treatment outcomes based on the regularity of the dosing interval. Results: Among 95 patients investigated, 63 (66.3%) received biologics at regular dosing intervals. We observed no significant intergroup differences in the final Psoriasis Area Severity Index (PASI) scores (1.2 vs. 1.8, p=0.16) and in the percentage improvement in PASI scores from baseline levels (−89.8% vs. −90.8%, p=0.68). The rate at which biologics were switched was higher in the irregular-dosing group than in the regular-dosing group; however, the difference was statistically nonsignificant (28.1% vs. 12.7%, p=0.06). We observed a significant intergroup difference in patients who were administered guselkumab at baseline (12 [21.8%] vs. 0 [0.0%], p=0.01). Conclusion This study showed that compared with regular dosing intervals, irregular dosing intervals of biologics were associated with high rates of switching of these agents, although we observed no statistically significant differences with regard to PASI scores. Therefore, it is important to adhere to the standard dosing schedule prescribed for biologics, and guselkumab may improve patient compliance.

Pembrolizumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death (PD)-1 receptor. Although it has a dramatic effect on the treatment of advanced malignancies, instability of immune tolerance may cause immune-related adverse events in the skin. A 62-year-old male with a history of metastatic urothelial carcinoma was referred to the dermatology department and presented with a widespread mucocutaneous rash. Itching appeared 7 days after the first administration of pembrolizumab, and on the third day after the second administration, an erythematous maculopapular rash that coalesced into large flaccid bullae on the whole body with a positive Nikolsky’s sign developed. A biopsy revealed a subepidermal bulla with basal keratinocyte necrosis. Pembrolizumab was discontinued due to the diagnosis of toxic epidermal necrolysis (TEN), and intravenous methylprednisolone was started. Herein, we report a case of TEN induced by pembrolizumab to highlight immune-related cutaneous adverse events in patients receiving anti-PD-1 therapy.