Prospective Longitudinal Study of Dynamics of Human Papillomavirus 6 and 11 Infection in Anogenital Hairs and Eyebrows of Male Patients with Anogenital Warts and Age-Matched Controls.

To better understand the natural history of anogenital warts (AGWs) and the dynamics of HPV6/11 infection in regional hairs, 32 newly diagnosed male patients with AGWs and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months), 43 AGW tissues and 1232 anogenital and eyebrow hair samples were collected. This is the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standards of care. The HPV6/11 prevalence was 19.9% in the patients' hair samples (HPV6 B1 in 53.1%) and 0% in the controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and the lowest in eyebrows (7.1%). The odds of having HPV6/11-positive hairs increased with smoking, shaving the anogenital region, and age. A close association between HPV6/11 presence in hairs and clinically visible AGWs was observed. The proportion of patients with visible AGWs and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with an increased AGW recurrence, but the sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of the AGW patients experienced one and two or more post-initial AGW episodes, respectively. The patients with HPV6/11-positive hairs or visible AGWs at a preceding visit demonstrated substantially higher odds of presenting with visible AGWs at a subsequent visit.

Fetal death from SARS-CoV-2 mediated acute placental failure.

INTRODUCTION: We demonstrate the nonlinear severity of symptoms of SARS-CoV-2 infection in the mother leading to fetal death after acute placental failure. METHODS: Careful clinical evaluation, real-time RT-PCR molecular microbiologic testing, isolation of a viable virus, and autopsy with histologic results were used to investigate the possible vertical transmission of SARS-CoV-2 infection from mother to fetus. RESULTS: Histologic changes in the placenta correlate with SARS-CoV-2 infection. Total nucleic acid isolated from vaginal swabs, fresh placental tissue, and deparaffinized tissue showed a high viral load of SARS-CoV-2. Complete genome sequencing confirmed the presence of the SARS-CoV-2 Delta variant. DISCUSSION: Several methods have been used to confirm SARS-CoV-2-mediated acute placental failure, all of which were conclusive. It should be noted that careful periodic fetal well-being checks are required in women infected with SARS-CoV-2, regardless of the severity of symptoms. Most of the cases described with fetal death occurred in the third trimester.

Vulvar Lichen Planus Presenting as Chronic Vulvar Purpura.

Background: There is a broad spectrum of vulvar pigmented lesions that differ based on their histopathological and clinical features. Chronic vulvar purpura is a rare entity, associated with a broad morphological spectrum, from lichen aureus, Zoon's vulvitis, pigmented purpuric dermatosis and with lichen planus as in our case. Case presentation: In this article we discuss a case of an 86-year-old white woman with hyperpigmentation on her upper vulva, next to the introitus, with complaints of urine incontinence. Biopsy revealed subepithelial stromal lichenoid inflammatory infiltrate containing plasma cells, lymphocytes and some neutrophilic granulocytes as well as dilated and congested vessels. Hemosiderin deposits and erythrocyte extravasation were found. There was evidence of hyperkeratosis with hyper granulosis and erosions. Spongiosis was also noted. Few melanocytes were identified with no sign of malignancy. These findings correlate with the diagnosis of vulvar lichen planus. Conclusions: Chronic vulvar purpura is a clinical term used for different chronic inflammatory dermatoses presenting as red bluish or violaceous discolorations on the vulva, often associated with cayenne-pepper-like speckling. Considering a great overlap of possible diseases, the final diagnosis could be challenging. It is important to exclude a melanocytic tumour in these cases.

Atorvastatin-induced Lupus Erythematosus Tumidus: A Case Report and Literature Review.

Lupus erythematosus tumidus (LET) is a rare photosensitive skin disease classified as a separate subtype of cutaneous lupus erythematosus. Clinically, it is characterized by erythematous plaques on sun-exposed areas. Typical histopathological findings are perivascular and periadnexal lymphohistiocytic infiltrates and prominent mucin deposition in the dermis. Treatment is based on photoprotection, topical corticosteroids, and antimalarial drugs. The exact pathogenesis of the disease is unknown. Drugs are considered a minor risk factor for the development of LET. We present a case of a 56-year-old woman who developed LET after starting treatment with atorvastatin. We describe her clinical course and review the literature concerning the cutaneous adverse reactions induced by statin drugs. To our knowledge, this is the first case of statin-induced LET. We conclude that statins can induce LET and that it is important for clinicians to be aware of this potential adverse effect associated with statins.

Wells' syndrome possibly caused by hematologic malignancy, influenza vaccination or ibrutinib: A case report.

BACKGROUND: Wells' syndrome (eosinophilic cellulitis) is an uncommon eosinophilic dermatosis of uncertain pathogenesis, characterized by clinical polymorphism and suggestive but nonspecific histopathologic traits. Its course is recurrent, and response to therapy is unpredictable. In a case in which the patient has a number of potential triggers for the manifestation of Wells' syndrome skin rash, the treating physician must decide or must make an assumption in order to establish the most likely clinical scenario. This is important for the patient's future treatment plans. CASE SUMMARY: We describe the clinical case of a 46-year-old female with chronic lymphocytic leukemia who had already received treatment for several months with ibrutinib. She was diagnosed with Wells' syndrome 10 d after an influenza vaccination containing thimerosal. Based on the literature, the patient was treated with a course of oral steroids. Resolution of clinical symptoms and rash were observed in response to the treatment. Ibrutinib was not discontinued. CONCLUSION: The etiology of Wells' syndrome remains unknown. Clinically, it resembles bacterial cellulitis. Lack of response to antibiotic treatment should lead the physician to consider a diagnosis of Wells' syndrome. Treating the underlying condition is important and may lead to resolution of the syndrome. However, the most common and effective treatment to limit the course of the disease are systemic steroids.

An Improved Protocol for Comprehensive Etiological Characterization of Skin Warts and Determining Causative Human Papillomavirus Types in 128 Histologically Confirmed Common Warts.

Human papillomaviruses (HPVs) are etiologically associated with various benign and malignant neoplasms of cutaneous and mucosal epithelia. We describe an improved diagnostic protocol for comprehensive characterization of causative HPV types in common warts, in which broad-spectrum PCRs followed by Sanger sequencing, two previously described and seven newly developed type-specific quantitative real-time PCRs (qPCRs) coupled with the human beta-globin qPCR were used for: (i) diagnosis of HPV infection in warts; (ii) estimation of cellular viral loads of all HPV types detected; and (iii) determination of their etiological role in 128 histologically confirmed fresh-frozen common wart tissue samples. A total of 12 different causative HPV types were determined in 122/126 (96.8%) HPV-positive warts, with HPV27 being most prevalent (27.0%), followed by HPV57 (26.2%), HPV4 (15.1%), HPV2 (13.5%), and HPV65 (7.9%). The cellular viral loads of HPV4 and HPV65 were estimated for the first time in common warts and were significantly higher than the viral loads of HPV2, HPV27, and HPV57. In addition, we showed for the first time that HPV65 is etiologically associated with the development of common warts in significantly older patients than HPV27 and HPV57, whereas HPV4-induced warts were significantly smaller than warts caused by HPV2, HPV27, HPV57, and HPV65.

Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma: A case report.

BACKGROUND: The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature. CASE SUMMARY: A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated. CONCLUSION: The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.

Histological Skin Remodeling Following Autologous Fibroblast Application.

The aim of this study was to quantify the effectiveness of intradermal application of autologous fibroblasts on lean tissue structures. The histological sections of the skin were analysed and evaluated for the expansion potential of autologous fibroblasts in the control skin patch area and the nearby pre-treated skin patch into which we had injected expanded autologous fibroblasts nine month earlier. The results show that the pre-injection of fibroblasts into the dermis leads to a long-term rejuvenation of the skin, as evaluated from the histological appearance and from the significantly increased density of fibroblasts in the pre-injected skin vs. controls, from around 60% to over 80%, determined as the percent of lean tissue by a novel image analysis approach. Interestingly, the rate of the in vitro fibroblast expansion from the pre-injected area of the skin was reduced in comparison with the controls, consistent with the view that fibroblasts exhibit a limited cell-division potential and that fibroblasts from the pre-injected skin already experienced expansion nine month earlier prior to the injection into the skin. We conclude that autologous fibroblast application results in a significant long-term augmentation of the lean tissue elements of the skin.

Purple-brown coalescing macules on the mandibular area of the face.

This patient presented with a 1-year history of violaceous-brown, coalescing reticulated macules on his face, with no similar lesions in other body areas. Laboratory findings were normal and antinuclear antibody test was negative. Histopathological findings included lichenoid tissue reaction and prominent pigmentary incontinence. Click here for the corresponding questions to this CME article.

Diagnostic challenge of Strongyloides stercoralis hyperinfection syndrome: a case report.

Strongyloides stercoralis causes chronic, mostly asymptomatic infections but hyperinfection syndrome may occur in immunosuppressed patients, especially in those receiving corticosteroids. We report a case of S. stercoralis hyperinfection syndrome in a solid organ transplant recipient that occurred approximately 2.5 months after heart transplantation. The patient presented to the intensive care unit with acute respiratory distress, bacteremia, and petechial rash on abdomen and toe. Microbiology testing of respiratory samples excluded infection with Pneumocystis jirovecii, respiratory viruses, pathogenic bacteria and fungi. No eosinophilia was found. Histopathological examination of the skin biopsy of the petechial rash provided the first indication of the diagnosis, revealing the presence of isolated filariform S. stercoralis larvae in the dermis. Subsequent microbiology testing confirmed the diagnosis. This case highlights the role of histopathological examination of a skin rash in diagnosing patients with atypical clinical presentation of Strongyloides hyperinfection syndrome.

Cutaneous leukocytoclastic vasculitis following COVID-19 vaccination with Ad26.COV2.S vaccine: a case report and literature review.

Cutaneous vasculitis is a recognized and potentially serious adverse event of immunization with several vaccines, and COVID-19 vaccines are no exception. We present a case of cutaneous leukocytoclastic vasculitis occurring 17 days after inoculation with adenoviral vector vaccine (Ad26.COV2.S) in a previously healthy 30-year-old patient with no history of prior adverse events following vaccination. Transient laboratory abnormalities (mild proteinuria, cryoglobulinemia, and slightly diminished C3 complement level) were also noted, but they resolved with the resolution of skin changes after treatment with topical steroids. Although the frequency of cutaneous vasculitis after COVID-19 vaccines is extremely low, it presents an important challenge for the clinician when faced with an uncertain and delicate decision whether these patients can safely receive booster doses of COVID-19 vaccine. Because vaccination certificates are necessary for day-to-day activities and have a limited validity date, this may be an uncomfortable issue.

Palisaded neutrophilic granulomatous dermatitis in a patient with HLA-B27-negative axial spondyloarthritis: a case report and literature review.

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare histopathological pattern belonging to a group of cutaneous granulomatous eruptions that typically manifests with asymptomatic skin-colored, erythematous, or violaceous papules or nodules. PNGD can be triggered by various systemic conditions, including medications and autoimmune and autoinflammatory disorders, as well as malignancies; for example, lymphoproliferative disorders. Therefore, in patients with PNGD an extended diagnostic workup is mandatory as well as follow-up in the case of idiopathic PNGD. To the best of our knowledge, this is the first reported case in the literature of PNGD causally related to a relapse of HLA-B27-negative axial spondyloarthritis.

Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.

Dystrophic Epidermolysis Bullosa Inversa - Case Report and Review of the Literature.

Dystrophic epidermolysis bullosa inversa is a very rare subtype of inherited dystrophic epidermolysis bullosa with a unique clinical manifestation. Generalized blistering in the neonatal period and in early infancy improves with age, with lesions becoming restricted to intertriginous areas, axial parts of the trunk, and mucous membranes. In contrast to other variants of dystrophic epidermolysis bullosa, the inverse type has a more favorable prognosis. We present a case of a 45-year-old female patient with dystrophic epidermolysis bullosa inversa, diagnosed in adulthood based on typical clinical presentation, transmission electron microscopic findings, and genetic analysis. Additionally, genetic analysis revealed that the patient also suffered from Charcot-Marie-Tooth disease, a hereditary motor and sensory neuropathy. To our knowledge, the coexistence of these two genetic diseases has not been reported so far. We describe clinical and genetic findings in the patient and review previous reports on dystrophic epidermolysis bullosa inversa. A possible temperature-related pathophysiology for the peculiar clinical manifestation is discussed.

The Influence of Fusarium Mycotoxins on the Liver of Gilts and Their Suckling Piglets.

Mycotoxins are common fungal secondary metabolites in both animal feed and human food, representing widespread toxic contaminants that cause various adverse effects. Co-contamination with different mycotoxins is frequent; therefore, this study focused on feed contaminated with Fusarium mycotoxins, namely, deoxynivalenol (5.08 mg/kg), zearalenone (0.09 mg/kg), and fusaric acid (21.6 mg/kg). Their effects on the liver of gilts and their piglets were chosen as the research subject as pigs are one of the most sensitive animal species that are also physiologically very similar to humans. The gilts were fed the experimental diet for 54 ± 1 day, starting late in their pregnancy and continuing until roughly a week after weaning of their piglets. Livers of gilts and their piglets were assessed for different histopathological changes, apoptosis, and proliferation activity of hepatocytes. On histopathology, gilts fed the experimental diet had a statistically significant increase in hepatocellular necrosis and apoptosis (p = 0.0318) as well as sinusoidal leukocytosis with inflammatory infiltrates of hepatic lobules (p = 0.0004). The amount of interlobular connective tissue in the liver of experimental gilts was also significantly decreased (p = 0.0232), implying a disruption in the formation of fibrous connective tissue. Apoptosis of hepatocytes and of cells in hepatic sinusoids, further assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, showed a statistically significant increase (p = 0.0224 and p = 0.0007, respectively). No differences were observed in piglet livers. These results indicated that Fusarium mycotoxins elicited increased apoptosis, necrosis, and inflammation in the liver of gilts, but caused no effects on the liver of piglets at these concentrations.

Primary Hepatic Leiomyoma in a Healthy Middle-Aged Woman: Literature Review and Case Report.

Introduction: Primary hepatic leiomyoma (PHL) is a rare benign hepatic tumor with unclear pathogenesis. It more commonly occurs in immunosuppressed patients, while only 24 cases have been described among immunocompetent individuals. To date, only one successful preoperative diagnosis of PHL has been achieved. Case Presentation: Here we report a case of PHL in a middle-aged woman with no history of immunosuppression. Preoperative diagnosis of PHL was established using ultrasound-guided fine needle trucut biopsy (FNTB). Nevertheless, due to the growing nature of tumor and patient's symptoms, we proceeded with surgical resection, which confirmed the diagnosis of PHL. At 6-month follow up, the patient is in good condition with no evidence of tumor recurrence. Conclusions: PHL is an uncommon tumor that should be considered in the differential diagnosis of rare liver tumors. Image guided FNTB appears to be effective in achieving preoperative diagnosis of PHL. Surgical resection, however, remains both diagnostic and curative in the management of PHL.

An Update on Molecular Genetic Aberrations in Spitz Melanocytic Proliferations: Correlation with Morphological Features and Biological Behavior.

The aim of the paper is to give an update on molecular genetic aberrations in Spitz melanocytic proliferations with special emphasis on their correlation with morphological features and biological behavior. The Spitz group of melanocytic proliferations is defined by a combination of distinctive morphological features and driver molecular genetic events. Morphologically, these neoplasms are characterized by large, oval, polygonal, or spindled melanocytes with abundant eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, often in association with epidermal hyperplasia. Molecular aberrations in Spitz melanocytic proliferations can be divided into two main groups, according to the driver genetic change: 1) 11p amplification/HRAS mutation, present in about 20% of cases, and 2) kinase fusions, present in about 50%, further subdivided into tyrosine kinase fusions (ALK, ROS1, NTRK1, NTRK3, MET, RET) or serine-threonine kinase fusions (MAP3K8, BRAF). Driver genetic aberrations can be detected along the whole biological spectrum of Spitz melanocytic proliferations, and are mutually exclusive. Although driver genetic aberrations enable proliferation of melanocytes, additional genetic events (often biallelic inactivation of CDKN2A and TERT promoter mutations) are necessary for the development of overt Spitz malignancy. CONCLUSIONS: Recent studies have demonstrated that certain driver genetic aberrations are more often associated with the benign spectrum of Spitz melanocytic proliferations and indolent biological behavior (11p amplification/HRAS mutation, tyrosine kinase fusions). In contrast, some driver aberrations are more frequent in the atypical/malignant spectrum of Spitz melanocytic proliferations with a potential for aggressive biological behavior (serine-threonine kinase fusions). In addition, certain driver aberrations are often associated with distinctive morphological features. However, none of the morphological features is entirely specific for any of these driver genetic aberrations. Immunohistochemistry for ALK, ROS1, and pan-TRK can be used for screening purposes to detect corresponding fusion proteins.

Fibroma of tendon sheath is defined by a USP6 gene fusion-morphologic and molecular reappraisal of the entity.

Fibroma of tendon sheath (FTS) is an uncommon benign myofibroblastic neoplasm that arises in association with tenosynovial tissue. Fusions of the USP6 gene have been recently documented in a proportion of so-called "cellular FTS" but not in "classic FTS". It remains unknown whether FTS can be defined by a USP6 fusion, regardless of cellularity, and what are USP6 fusion-negative "cellular FTS". Furthermore, FTS with low cellularity seems to be frequently confused with desmoplastic fibroblastoma. We performed a comprehensive analysis, including targeted RNA sequencing, of 58 consecutive cases originally diagnosed as FTS (n = 49), desmoplastic fibroblastoma (n = 6), or nodular fasciitis (n = 3); the latter two at the predilection sites for FTS. After review of the original slides, 28 lesions were morphologically classified as FTS (13 "classic" and 15 "cellular") and 23 as desmoplastic fibroblastoma. Among originally diagnosed FTS at the more cellular end of the spectrum, we identified seven lesions that shared many morphologic features of FTS but, in addition, showed several distinct morphologic features consistent with myofibroma, such as myoid appearance, branching thin-walled vessels, and perivascular growth. Targeted RNA sequencing showed a USP6 fusion in 17 of 18 analyzed FTS, regardless of cellularity, 0 of 5 desmoplastic fibroblastomas and 0 of 4 myofibromas. MYH9, COL1A1, and ASPN were identified as fusion partners in three cases each, and MIR22HG, CTNNB1, SPARC, CAP1, EMP1, LINC00152, NR1D1, and RAB1A in a single case each. FTS, regardless of cellularity, can be defined by a USP6 fusion with a variety of fusion partners. More cellular lesions exhibiting some morphologic features of FTS but lacking a USP6 fusion tend to be myofibromas.