Increased WT1 mRNA levels are pervasive in acute myeloid leukemia (AML), and this marker has been used to assess the leukemic compartment size after chemotherapy or hematopoietic cell transplants. Little is known about the effects of WT1 on the leukemic cells and their targets. This work used data obtained from gene expression arrays performed on AML samples with high and low WT1 mRNA levels to pinpoint genes that WT1 can regulate. We singled out SGK1, which showed an inverse correlation between its mRNA levels and WT1 in leukemic cell lines and AML samples. In cellular models, forced expression of WT1 reduced mRNA and protein levels of SGK1. Furthermore, WT1 repressed the SGK1 promoter activity, and accordingly, WT1 knockdown showed an increased expression of SGK1. We also detected an inverse correlation between WT1 and SGK1 during leukemic cell-line differentiation. WT1 genetic knockdown displayed decreased cell viability under nutrient deprivation. By contrast, SGK1 knockdown or pharmacologic inhibition increased resistance to apoptosis in response to serum starvation, acting on cell cycle progression. The effects of SGK1 targeting in hematologic conditions merit further investigation.

A woman in her 60s with previous breast carcinoma, currently in remission, presented with pruritic lesions on her chest, arms, and back. What is your diagnosis?

(A) Correlation matrix of unsupervised co-regulated genes, based on the 208 genes included in the NanoString platform. Some of the clusters of co-regulated genes corresponded to the following: Inflammatory cells; Epstein-Barr virus; B-cells; Cytotoxic T-cells; T-cells; and Proliferation. (B) Analysis of genomic alterations by targeted sequencing. Distribution of mutations in the 62 analyzed genes. Rows correspond to sequenced genes, columns represent individual patients. Color coding: green, missense; blue, synonymous; pink, frameshift; violet, Indel; red, stop gained; yellow, UTR.

Proliferative nodules (PNs) are benign nodular proliferation of melanocytes occurring within congenital melanocytic naevi (CMN). Differential diagnosis between PN and melanoma is challenging for clinicians and pathologists. We describe the case of a 9-month-old boy who developed multiple nodules arising in a medium-sized CMN. Clinically, pink papules were observed, with dotted vessels on dermoscopy, suggesting spitzoid PN. On histopathological examination, the dermoscopic findings correlated with the vertical vessels of a spitzoid PN. Dermoscopy could be a useful tool to differentiate PN from melanoma. However, further studies describing the dermoscopic features of the different PN subtypes are needed. Histopathology remains the gold standard for definitive diagnosis aided by ancillary molecular tests such as fluorescence in situ hybridization or comparative genomic hybridization.

Generalized pustular psoriasis (GPP) represents the rarest form of psoriasis, which may be potentially fatal. In the last decade, (likely) pathogenic variants in the IL36RN, CARD14 and AP1S3 genes have been associated with monogenic GPP forms. Despite these advances, the genetic basis of most patients with GPP remains unidentified. Treatment of GPP patients is often difficult, with no consensus about the best available options to date. We report herein an infant with severe GPP in whom the disease started at the age of 2 months. Genetic investigations identified a heterozygous pathogenic variant in the IL36RN gene associated with a heterozygous variant of uncertain significance in the CARD14 gene. After previous treatment failures with acitretin, cyclosporin and anakinra, treatment with the interleukin‐17 antagonist secukinumab resulted in a dramatic and prompt positive response that persisted at 12‐month follow up. According to our experience, we believe secukinumab can be an effective and safe treatment for pediatric patients with GPP even before 1 year of age.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity associated with habitual chewing of quid, with a high incidence among populations of the Indian subcontinent and Southeast Asia. Clinically, its initial manifestation may mimic oral lichen planus or lichen sclerosus. If the habit is not halted, the mucosa gets leathery and thickened, and fibrous bands form causing significant morbidity. Microscopically, it is characterized by atrophic epithelium, loss of rete ridges, and hyalinization of lamina propria. Of note, these hallmark histopathological features may be overlooked in the unusual presence of lichenoid interface changes, which may lead to the wrong diagnosis. We present herein five cases in which the rare joint appearance of OSF and lichenoid reaction features posed a diagnostic challenge. Due to its progressive nature and malignant potential, the presence of oral lichenoid changes overlying submucous hyalinization, in the right clinical and demographic setting, should raise suspicion of OSF and prompt actions directed at quid-chewing discontinuation.

International Journal of DermatologyVolume 59, Issue 4 p. e96-e98 Clinicopathologic challenge Purple ulcerated nodules in a middle-aged man Cristina López-Sánchez MD, Corresponding Author Cristina López-Sánchez MD clopezsan@santpau.cat Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain Correspondence Cristina López-Sánchez, MD Dermatology Department Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Sant Antoni Maria Claret 167 08025, Barcelona Spain E-mail: clopezsan@santpau.catSearch for more papers by this authorHelena Iznardo MD, Helena Iznardo MD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorAna Mozos MD, Ana Mozos MD Department of Pathology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorVíctor Flores-Climente MD, Víctor Flores-Climente MD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorLluís Puig MD, PhD, Lluís Puig MD, PhD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this author Cristina López-Sánchez MD, Corresponding Author Cristina López-Sánchez MD clopezsan@santpau.cat Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain Correspondence Cristina López-Sánchez, MD Dermatology Department Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Sant Antoni Maria Claret 167 08025, Barcelona Spain E-mail: clopezsan@santpau.catSearch for more papers by this authorHelena Iznardo MD, Helena Iznardo MD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorAna Mozos MD, Ana Mozos MD Department of Pathology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorVíctor Flores-Climente MD, Víctor Flores-Climente MD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorLluís Puig MD, PhD, Lluís Puig MD, PhD Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this author First published: 13 January 2020 https://doi.org/10.1111/ijd.14771 Conflict of interest: None. Funding source: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume59, Issue4April 2020Pages e96-e98 RelatedInformation

bucil and rituximab was referred to the dermatology department for asymptomatic swelling and red discoloration of nipples and ears that had developed over a few months. No fever, malaise, or other systemic symptoms were reported, and there was no known history of a tick or insect bite. His medical history was significant for lung cancer treated with surgery and chemotherapy 5 years before. Physical examination disclosed polypoid “raspberrylike” erythematous tumors on both nipples: 2 erythematoviolaceous nodules on the chest and soft and nontender erythematous nodules on both helix and earlobes. The rest of the physical examination was unremarkable. Laboratory investigations were significant for leukocytosis and anemia, with a white blood cell count of 498.3 cells/mL (85% lymphocytes) and a hemoglobin of 12.1 g/dL (normal value 13–17 gr/dL). Serology for Borrelia burgdorferi was positive for immunoglobulin G (indirect immunofluorescence assay) but negative for IgM antibodies (Fig. 1). FIGURE 1. Clinical image: erythematous nodules on both ears, “raspberry-like” tumors on nipples and erythematoviolaceous nodules on the chest.

López-Sánchez, Cristina MD*; Fumagalli, Caterina MD†; Mozos, Ana MD†; Flores-Climente, Víctor MD*; Rozas-Muñoz, Eduardo MD* Author Information

Rozas Muñoz, Eduardo MD*; Mir-Bonafé, Juan Francisco MD*; Mozos, Ana MD, PhD†; Szafranska, Justyna MD†; Puig, Luis MD, PhD*Author Information

The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies. Here, we describe that CXCR7 receptor is an independent prognostic factor that associates with good clinical outcome. Moreover, the expression of CXCR7 associates with increased survival in CXCR4+ but not in CXCR4- DLBCL patients. Thus, the combined immunohistochemical evaluation of both CXCR7 and CXCR4 expression in DLBCL biopsies may improve their prognostic value as single markers. Finally, we show that CXCR7 overexpression in vitro is able to diminish DLBCL cell survival and increase their sensitivity to antitumor drugs. Hence, further studies on the CXCR7 receptor may establish its role in DLBCL and the molecular mechanisms that modulate CXCR4 activity.

Mucocutaneous candidiasis is a common infection affecting both immunocompetent and immunosuppressed individuals. Diversity in the clinical and histopathological presentation of mucocutaneous candidiasis is well known. However, the occurrence of cutaneous verrucous lesions and giant yeast-like structures has been rarely reported. In this article, we describe a case of disseminated mucocutaneous candidiasis in an immunosuppressed patient who presented as a verrucous plaque on the scrotum with giant Candida blastoconidia. This peculiar presentation expands the clinicopathological spectrum of mucocutaneous candidiasis and highlights the wide range of clinical manifestations and great morphologic variability of this common fungal infection.

Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14; 18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14: 18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14; 18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <.001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =.075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14; 18)(-) FL displayed a mutational profile similar to t(14; 18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14; 18)(-) FL in adults indicate that these are two different disorders.

Breast carcinomas rarely metastasize to the ovary and are even more rarely present clinically as primary ovarian tumors. However, patients with breast cancer not infrequently develop independent primary ovarian carcinomas. In these cases, distinction between independent primaries and metastatic tumors is crucial. Several comparative immunohistochemical studies have been reported, but few included significant clinicopathologic data and none investigated cases of ovarian and breast carcinomas from the same patients. In this study, we compared 18 cases of patients with bona fide independent breast and ovarian carcinomas (15 high-grade serous and 3 clear cell carcinomas), with 9 cases of patients with known mammary carcinomas (7 lobular and 2 ductal carcinomas) metastatic to the ovary. Immunohistochemical stains for Pax-8, WT-1, and GATA3 were carried out on tissue microarrays (TMA). Most primary ovarian carcinomas were larger than the metastatic tumors (P=0.001) and were diagnosed at an advanced stage. All primary ovarian tumors showed marked nuclear pleomorphism, whereas only 2 metastatic breast carcinomas had Grade 3 nuclei (P=0.000). The vast majority of ovarian metastases (7/9) showed the typical pattern of lobular breast carcinoma. Pax-8 and WT-1 expression were found in 16 of 18 (88%) and 13 of 18 (72%) primary ovarian carcinomas, respectively. In contrast, all primary ovarian carcinomas were negative for GATA3. The 2 Pax-8-negative ovarian carcinomas were also negative for WT-1. With the exception of 3 triple-negative carcinomas, all primary breast carcinomas were positive for GATA3. All metastatic breast carcinomas were positive for GATA3 and negative for Pax-8. WT-1 expression was seen in only 1 of 9 metastatic breast carcinomas (11%). Patients with ovarian metastases had worse prognosis than patients with independent breast and ovarian carcinomas (P=0.000). Pax-8, WT-1, and GATA3 immunoreactions are useful in the distinction between independent primaries and metastatic mammary carcinomas to the ovary in the light of clinicopathologic findings.

The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma ( DLBCL ) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD / SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100 , decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd