Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study.

BACKGROUND: Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. OBJECTIVE: to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. METHODS: Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). RESULTS: Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. CONCLUSION: This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.

Kaposi Sarcoma of the Nail Unit: A Case Report and Review of the Literature.

Introduction: Kaposi sarcoma is an angioproliferative neoplasm. Its manifestations are well known but nail involvement seems extremely underreported. Case Presentation: A 55-year-old man presented with a 6-month history of a growing subungual tumor affecting the third right toe. After surgical excision, histological examination revealed a Kaposi sarcoma. Discussion: We report a case of Kaposi sarcoma with nail involvement of only one toe as the first and unique manifestation, which is exceptional.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Histologic Patterns and Clues to Autoinflammatory Diseases in Children: What a Cutaneous Biopsy Can Tell Us.

Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of 'complex multigenic diseases' are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the 'neutrophilic' pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet's syndrome; (ii) the 'vasculitic' pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the 'granulomatous' pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation.

Robotic assisted laparoscopic partial nephrectomy using contrast-enhanced ultrasound scan to map renal blood flow.

OBJECTIVE: The paper describes novel real-time 'in situ mapping' and 'sequential occlusion angiography' to facilitate selective ischaemia robotic partial nephrectomy (RPN) using intraoperative contrast enhanced ultrasound scan (CEUS). MATERIALS AND METHODS: Data were collected and assessed for 60 patients (61 tumours) between 2009 and 2013. 31 (50.8%) tumours underwent 'Global Ischaemia', 27 (44.3%) underwent 'Selective Ischaemia' and 3 (4.9%) were removed 'Off Clamp Zero Ischaemia'. Demographics, operative variables, complications, renal pathology and outcomes were assessed. RESULTS: Median PADUA score was 9 (range 7-10). The mean warm ischaemia time in selective ischaemia was less and statistically significant than in global ischaemia (17.1 and 21.4, respectively). Mean operative time was 163 min. Postoperative complications (n = 10) included three (5%) Clavien grade 3 or above. Malignancy was demonstrated in 47 (77%) with negative margin in 43 (91.5%) and positive margin in four (8.5%). Long-term decrease in eGFR post selective ischaemia robotic partial nephrectomy was less compared with global ischaemia (four and eight, respectively) but not statistically significant. CONCLUSIONS: This technique is safe, feasible and cost-effective with comparable perioperative outcomes. The technical aspects elucidate the role of intraoperative CEUS to facilitate and ascertain selective ischaemia. Further work is required to demonstrate long-term oncological outcomes. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd.

Optimizing prostate specimen handling for diagnosis and prognosis.

Optimal processing, handling, and sampling of prostatic biopsies, transurethral resections, and radical prostatectomy specimens ensure accurate diagnosis and staging. Prognostic factors derived from careful examination of tissue samples are critical for patient management, including cancer volume, extraprostatic extension, surgical margins, vascular/lymphatic invasion, and perineural invasion. This chapter addresses these important issues, including recent recommendations of a consensus panel of the International Society of Urologic Pathologists.

Prostatic stromal hyperplasia with atypia: follow-up study of 18 cases.

CONTEXT: Prostatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei. OBJECTIVE: To determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia. DESIGN: Eighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.). RESULTS: Prostatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5-14 years), but none developed evidence of sarcomatous transformation or malignancy. CONCLUSIONS: Prostatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.

Prostatic leiomyoma with atypia: follow-up study of 10 cases.

We studied the clinical and histologic features of 10 cases of prostatic leiomyoma with atypical bizarre nuclei. Immunohistochemical studies were undertaken in 6 cases. Patient follow-up was obtained in all cases. Patients ranged in age from 50 to 82 years (mean, 65 years) and presented with urinary obstructive symptoms in 7 cases, abnormal digital rectal examination in 3 cases. The histologic findings consisted of a solid circumscribed expansile stromal nodule with abundant smooth muscle and variable numbers of atypical bizarre giant cells. The cells of the tumor displayed intense immunoreactivity for desmin, actin, and androgen receptor and weak to moderate reactivity for vimentin. Four local recurrences were seen, with a follow-up for 3 to 16 years (mean, 7.4 years), but no evidence of sarcomatous transformation occurred. Despite worrisome histologic appearance, a benign clinical behavior was seen in all cases.

Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors.

Organic cation transporter 3/4 (OCT3/4) is a transcription factor of embryonic stem cells; c-kit (CD117) is a tyrosine kinase receptor implicated in seminoma carcinogenesis. Their reactivity is well characterized in testicular, but not extragonadal and metastatic, germ cell tumors. A total of 93 germ cell tumors (41 seminoma, 22 embryonal carcinoma, 18 teratoma, and 12 yolk sac tumor) were obtained from the central nervous system (30), mediastinum (23), retroperitoneum/abdomen (31), and other locations (9). Immunohistochemical staining for c-kit, placental-like alkaline phosphatase (PLAP), OCT3/4, and new markers D2-40 and AP-2gamma was performed on seminomas; CD30 and epithelial membrane antigen were added for nonseminomas. In embryonal carcinoma, c-kit reacted in 17 of 22 cases, OCT3/4 in 18 of 22, and PLAP in 13 of 22. OCT3/4 was superior to PLAP in intensity and percent cells staining. In seminoma, OCT3/4 and D2-40 were superior to PLAP in intensity and percent cells; c-kit and AP-2gamma were superior in percent cells. D2-40 stained 23 of 24 seminomas strongly but had only weak focal reactivity in 6 of 17 embryonal carcinomas. Sensitivity and specificity were high for OCT3/4 discriminating seminoma and embryonal carcinoma, and c-kit discriminating seminoma, from other germ cell tumors. For embryonal carcinoma, OCT3/4 had higher specificity (0.94) than CD30 (0.786) owing to CD30 reactivity in 3 of 10 teratomas. Epithelial membrane antigen discriminated teratoma from other nonseminomas with a sensitivity of 1 but reacted occasionally in embryonal carcinoma (3/15) and yolk sac tumor (2/7). In conclusion, for extragonadal seminoma, OCT3/4, AP-2gamma, D2-40, and c-kit were equivalently superior to PLAP. For embryonal carcinoma, OCT3/4 was superior to PLAP and more specific than CD30. D2-40 is recommended to discriminate between seminoma and embryonal carcinoma.

A primer of endometrial cytology with histological correlation.

Cytology is an effective method for assessing benign endometrium and for discovering premalignant and malignant endometrial states. In addition, it is useful for diagnosing non-neoplastic abnormalities of the endometrium. This overview compares endometrial cytology to endometrial histology for a variety of benign, abnormal non-neoplastic, and neoplastic conditions; and, discusses both diagnostic criteria and pitfalls in the assessment of endometrial brushings specimens. It also makes an attempt to estimate levels of confidence in endometrial cytodiagnosis. When endometrial brushing is used in conjunction with other diagnostic techniques such as ultrasonography/sonohysterography or hysteroscopy, cytology becomes a sensitive case finding technique that shows good patient acceptance (because of a significant decrease in procedure-associated pain) and high diagnostic yield.

Improved filter method for urine sediment detection of urothelial carcinoma by fluorescence in situ hybridization.

CONTEXT: Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. The time required for slide preparation using the conventional cytospin method is lengthy. OBJECTIVE: To present an alternative to the conventional cytospin method. DESIGN: We compared the results of an improved filter monolayer method with published results of the conventional cytospin method. A total of 624 patients with cytology and FISH analyses were followed with cystoscopy and/or bladder biopsy. Fluorescence in situ hybridization analysis was performed on 624 cases using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. RESULTS: A total of 217 (34.7%) of 624 patients had follow-up bladder biopsies, and 170 of these (78.3%) had urothelial carcinoma. The sensitivity for cancer detection was higher for FISH than for urine cytology (92.9% [158/ 170] for FISH vs 72.9% [124/170] for urine cytology, P = <5%). The specificity was equivalent for FISH and urine cytology (97.5% [443/454] for FISH vs 92.2% [419/454] for cytology). The sensitivity for FISH was better (92.9% vs 81%), and there was no significant difference in specificity (97.5% vs 96%) between the filter method and the conventional cytospin method. Unlike the conventional cytospin method, the filter method did not require multiple centrifugation and decantation steps or investment in dedicated equipment. CONCLUSIONS: The improved filter method was faster, easier, and less expensive than published results with the conventional cytospin method with better sensitivity and equivalent specificity.

Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis.

CONTEXT: The separation of chromophobe renal cell carcinoma, oncocytoma, and clear cell renal cell carcinoma using light microscopy remains problematic in some cases. OBJECTIVE: To determine a practical immunohistochemical panel for the differential diagnosis of chromophobe carcinoma. DESIGN: Vimentin, glutathione S-transferase alpha (GST-alpha), CD10, CD117, cytokeratin (CK) 7, and epithelial cell adhesion molecule (EpCAM) were investigated in 22 cases of chromophobe carcinoma, 17 cases of oncocytoma, and 45 cases of clear cell carcinoma. RESULTS: Vimentin and GST-alpha expression were exclusively observed in clear cell carcinoma. CD10 staining was more frequently detected in clear cell carcinoma (91%) than in chromophobe carcinoma (45%) and oncocytoma (29%). CD117 was strongly expressed in chromophobe carcinoma (82%) and oncocytoma (100%), whereas none of the cases of clear cell carcinomas were immunoreactive. Cytokeratin 7 was positive in 18 (86%) of 22 cases of chromophobe carcinoma, whereas all oncocytomas were negative for CK7. EpCAM protein was expressed in all 22 cases of chromophobe carcinoma in more than 90% of cells, whereas all EpCAM-positive oncocytomas (5/17; 29%) displayed positivity in single cells or small cell clusters. CONCLUSIONS: Using the combination of 3 markers (vimentin, GST-alpha, and EpCAM), we achieved 100% sensitivity and 100% specificity for the differential diagnosis of chromophobe carcinoma, oncocytoma, and clear cell carcinoma. The pattern of "vimentin(-)/GST-alpha(-)" effectively excluded clear cell carcinoma, and homogeneous EpCAM expression confirmed the diagnosis of chromophobe carcinoma rather than oncocytoma. CD117 and CK7 were also useful markers and could be used as second-line markers for the differential diagnosis, with high specificity (100%) and high sensitivity (90% and 86%, respectively).

Glutathione S-transferase: differential expression of alpha, mu, and pi isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.

Glutathione S-transferases (GST) comprise a family of enzymes which are critical for inactivation of toxins and carcinogens. We examined the cellular expression of multiple subclasses of GST immunohistochemically in 25 radical prostatectomy specimens with clinically localized prostate cancer. Gleason scores ranged from 5 to 9, and pathologic stages varied from pT2a to pT3b (all N0M0). Antibodies were directed against GST Ya, Yc, and Yk (alpha subclass), Yb1 (micro subclass), and YPr (pi subclass). The percentage of positive cells and intensity of staining was assessed for benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. GSTalpha (Ya) was detected in 30% of cells (mean) in benign acini, 4.9% of cells in high-grade PIN, and 4.5% of cells in adenocarcinoma. The corresponding results for alpha (Yk), micro (Yb1), and pi (Yp) were 12.7%, 10.9%, and 3.5%; 8.7%, 5.2%, and 0.6%; and 66.7,% 0%, and 0%, respectively. GST Yc (alpha subclass) displayed the lowest level of expression, with diffuse weak staining in scattered benign secretory cells and only single cells (<1%) in high-grade PIN and carcinoma. These results demonstrate consistent reduction or loss of expression of all subclasses of GST with progression of prostatic neoplasia from benign epithelium to high-grade PIN and carcinoma. We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST and other detoxifying and antimutagenesis agents.

Glutathione S-transferase pi (GSTP1) hypermethylation in prostate cancer: review 2007.

Prostatic carcinoma is characterised by the silencing of the pi-class glutathione S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of GSTP1 results from aberrant methylation at the CpG island in the promoter-5' and occurs in the vast majority of cases of high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancers. We review the potential novel role of GSTP1 and its related expression in prostate cancer. The loss of expression (silencing) of the GSTP1 gene is the most common (>90%) genetic alteration reported to date in prostate cancer. Quantitative methylation-specific PCR assays allow detection of GSTP1 methylation in prostate biopsies and may improve the sensitivity of cancer detection. Advances in the epigenetic characterisation of prostate cancer have enabled the development of DNA methylation assays that may soon be used in diagnostic testing of serum and tissue for prostate cancer. Inhibition of aberrant promoter methylation could theoretically prevent carcinogenesis.

Diagnosis of prostatic carcinoma after therapy.

CONTEXT: Prostate cancer is the most common cancer of men in the United States and is third only to lung and colon cancer as a cause of cancer death. In 2006, 27,350 Americans will die of prostate cancer, and 234,460 new cases will be diagnosed. Treatment changes in the benign and cancerous prostate create diagnostic challenges in pathologic interpretation, particularly in needle biopsy specimens and in evaluation of extraprostatic metastases. OBJECTIVE: To summarize therapy-related pathologic findings in the prostate with emphasis on recognition of treated adenocarcinoma. DATA SOURCES: Extensive review of published literature and the authors' experience. CONCLUSIONS: Following therapy for prostate cancer, it is critical that the clinician provide the pertinent history of androgen deprivation or radiation therapy to assist the pathologist in rendering the correct diagnosis.

Preoperative prediction of multifocal prostate cancer and application of focal therapy: review 2007.

Prostate cancer is a leading malignancy among men. Early prostate cancer is most commonly treated with radical surgery and radiotherapy. In the era of prostate-specific antigen and newly emerging highly specific screening tests, a greater number of men are given a diagnosis earlier in life, and disease is more often confined. Less-invasive treatments, such as focal therapy, are becoming increasingly popular, yielding shorter hospital stays, faster recovery, and fewer complications. Potential drawbacks to focal therapy include the risk of incomplete treatment, which may result from missed cancer foci and inadequate ablation to target tissues. Furthermore, this approach is not universally applicable to all patients--for example, those who have periurethral and extraprostatic extension of the tumor may not benefit from focal treatment. This article reviews the importance of multifocal prostate cancer and the application of focal treatment.

Atypical small acinar proliferation in the prostate: clinical significance in 2006.

About 2% of contemporary prostate needle biopsy specimens contain collections of small acini that are suspicious for cancer but that fall below the diagnostic threshold and are reported as atypical small acinar proliferation suspicious for but not diagnostic of malignancy. Prostate cancer has been identified in specimens from subsequent biopsies in up to 60% of cases of atypical small acinar proliferation, indicating that this finding is a significant predictor of cancer. Identification of atypical small acinar proliferation warrants repeat biopsy for concurrent or subsequent invasive carcinoma.