Cutaneous Nodules Research Articles

Acral Cutaneous Intraneural Pseudoperineurioma.

Several cutaneous neurovascular stromal lesions are clinically and pathologically ill-defined entities. They are known by different nomenclatures, often unrecognized, misinterpreted, and confused with other skin lesions. Reports have documented cases of palmar and oral lesions in both children and adults. There is uncertainty regarding their true prevalence, clinicopathologic characteristics, and classification. Our aim is to highlight the salient histopathologic, histochemical, and immunohistochemical features of acral nodular tumors showing perineuriomatous differentiation. We found 3 teenagers (0.2%) [2 females, 1 male, average age: 13 years] with hand nodules out of 1331 patients with cutaneous and oral polypoid lesions. They were isolated, asymptomatic, nontraumatic, subcentimetric, palmar, digital nodules with an average duration of 5 years. They demonstrated dermal-based anomalous growths composed of thick tortuous neurovascular bundles and collagenous fibrovascular stroma. Masson trichome demarcated micronodular and plexiform neurovascular bundles showing concentric onion-bulb whorls ensheathed in collagenous fibrovascular stroma. Elastic fibers were absent. Alcian blue demonstrated intraneural mucinous alteration and loose interstitial myxoid mesenchyme. CD31, ERG, and smooth muscle actin highlighted small intraneural capillary-sized, and larger venous and arteriolar interstitial vasculatures. CD34 decorated the interstitial mesenchyme. S100, SOX10, and neurofilament revealed sparse neural components, whereas EMA and GLUT1 highlighted prominent perineurial components within the neurovascular bundles and onion-bulb micronodules. The findings suggest that cutaneous intraneural pseudoperineurioma nodules may represent a distinct clinicopathologic entity among traumatic neuromas, resembling cutaneous intraneural perineurioma. Further validation studies are necessary because of the small size of the case series and the lack of molecular genetic studies.

Identifying Hereditary Leiomyomatosis and Renal Cell Cancer through Unobtrusive Cutaneous Nodules

Cutaneous leiomyomas (CLMs) are associated with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) syndrome (Mendelian Inheritance in Man [MIM]: 150800)—a rare genodermatosis caused by a heterozygous pathogenic variant in the fumarate hydratase (FH) gene. It is characterized by a predisposition to develop cutaneous and/or uterine leiomyomas and an aggressive type of renal cell carcinoma (RCC). We describe a 27-year-old male who presented with a painful nodule on the left upper arm persisting for 5 years and the subsequent emergence of painless nodules in various parts of the body over the past two years. A family history of RCC prompted suspicion of the HLRCC syndrome. Cutaneous examination revealed erythematous subcutaneous nodules, with histological analysis confirming CLM. Genetic testing identified a pathogenic variant in the FH gene, confirming the diagnosis of HLRCC. Management involved surgical excision of the symptomatic nodules and genetic counselling/testing for the proband and his family members. The long-term follow-up plan includes dermatological and nephrological surveillance with annual renal magnetic resonance imaging (MRI) scans. This report aims to enhance the awareness of this disease and highlight the role of cutaneous lesions in facilitating early detection.

Cutaneous nodules secondary to Mycobacterium avium complex in a patient with human immunodeficiency virus

Cutaneous nodules secondary to Mycobacterium avium complex in a patient with human immunodeficiency virus

A rapidly enlarging axillary nodule

We discuss the case of a previously well 40-year-old man who presented to dermatology with a short history of an unusual, rapidly enlarging, calcified cutaneous nodule.

A Case of Calciphylaxis

Introduction: Calciphylaxis (calcific uremic arteriolopathy), is a condition primarily observed in patients with end-stage renal disease (ESRD). Aim: To increase clinical awareness of calciphylaxis and to consider it a differential diagnosis in the presence of atypical skin nodules or ulcers occurring in patients with chronic kidney disease (CKD), especially in patients on hemodialysis and non-hemodialysis patients with the background of diabetes mellitus and secondary hyperparathyroidism. Case Report: We present the case of a 77-year-old woman with CKD and diabetes mellitus as well as severely painful, firm, indurated plaques on the lower extremities. The plaques progressed to involve larger areas with associated local ulceration and necrosis. Laboratory testing revealed hyperparathyroidism and incisional skin biopsy confirmed calciphylaxis. Conclusion: Each single CKD patient with diabetes mellitus and signs of secondary hyperparathyroidism with extremely painful ischemic cutaneous lesions or painful subcutaneous nodules without skin changes, although at times, pain may precede the development of the lesions, is a candidate for skin biopsy. Calciphylaxis is a rare but serious kidney complication. Keywords: calciphylaxis, chronic kidney disease, prognosis, treatment.

Regression of Clinically Diagnosed Ocular Kaposi Sarcoma Post-Initiation of Highly Active Antiretroviral Therapy

Kaposi sarcoma is a low-grade vascular neoplasm linked to the human herpesvirus 8, with the AIDS-associated epidemic variant being the most common and aggressive. Although Kaposi sarcoma more commonly affects the cutaneous tissues, lymph nodes, and visceral organs, it can also be present in ocular and ocular adnexal tissues. We report a case of a 58-year-old Indo-Caribbean woman living with AIDS who presented with a large upper eyelid mass that was clinically diagnosed as Kaposi sarcoma. After the recommencement of the patient’s highly active antiretroviral therapy (HAART), the lesion showed marked regression, highlighting the critical role of HAART in the management of Kaposi sarcoma. This is the first documented case of AIDS-associated ocular Kaposi sarcoma in the Eastern Caribbean region and underscores the need to consider Kaposi sarcoma as a differential diagnosis in patients living with HIV/AIDS who present with ocular or ocular adnexal masses.

Cutaneous plasmacytosis in a dog (Caninus familiaris)

AbstractCutaneous plasmacytosis is rarely reported in veterinary medicine, but far more described in human medicine. Extramedullary plasmacytomas are plasma cell tumours without bone marrow involvement. This study aimed to report a case of a 7‐year‐old, mixed‐breed dog with a presumptive diagnosis of cutaneous plasmacytosis. At clinical examination, the dog presented 15 cutaneous nodules disseminated through the body. Cytopathological analysis revealed plasmacytoma in 13 out of 15 nodules. Thoracic radiography revealed radiopaque structures suggestive of pulmonary nodules, and abdominal ultrasonography indicated suspicion of a hepatic neoplastic process. The animal died during the diagnostic screening period, with a survival of 16 days from the initial consultation. Thus, further confirmatory tests such as histopathology and immunohistochemistry were not performed, and the pulmonary and hepatic lesions were not assessed. This report demonstrates the importance of cytopathology in the presumptive diagnosis of cutaneous plasmacytosis in a dog, considering the absence of other complementary examinations.

Malignant Phyllodes Tumor of the Breast With Multiple Cutaneous Metastasis Resembling Pleomorphic Rhabdomyosarcoma.

Malignant phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm that shows variegated histomorphology and an aggressive clinical course. Cutaneous metastases are rare. A 68 year old woman presented with a palpable left breast mass identified on a routine breast exam. Mammogram showed an oval circumscribed heterogeneous mass measuring 3.7 × 3.7 × 2.7 cm. Patient underwent core needle biopsy with subsequent excision and received a diagnosis of malignant phyllodes tumor with rhabdomyosarcomatous elements with negative margins. The patient suffered a local recurrence 5 months later and was scheduled for re- excision; however prior to that procedure the patient represented to clinic with several cutaneous and subcutaneous nodules located on the left flank, left arm, and bilateral buttocks; described as itchy but not painful. Biopsies of the left flank and the left arm were performed and pathologic examination of both biopsies demonstrated a high- grade rhabdomyoblastic neoplasm that closely resembled so-called pleomorphic rhabdomyosarcoma. The tumor cells in both biopsies marked for immunohistochemical markers of rhabdomyoblastic differentiation and re-review of the original resection specimen showed identical areas confirming the skin and subcutaneous nodules as metastatic malignant phyllodes tumor. We report an unusual case of malignant PT with cutaneous metastases that demonstrated a pure rhabdomyosarcoma phenotype with pleomorphic morphology. Awareness that malignant PT may rarely involve cutaneous sites and present with a pure rhabdomyosarcomatous morphology is important for proper recognition and diagnosis of these tumors, as out of context they may be confused with sarcomas.

Isolation and Identification of Lumpy Skin Disease Virus.

Lumpy skin disease virus (LSDV), a member of the capripoxvirus genus, induces lumpy skin disease (LSD) in cattle and buffalo populations. The initial documentation of LSD dates back to 1929 in Zambia, with subsequent rapid dissemination within the cattle community in Africa and Asia. Described as the "smallpox" equivalent in cattle, LSD manifests through clinical features such as fever, extensive cutaneous nodules, body wasting, lymph node enlargement, and skin edema. Isolation of LSDV constitutes an important step in evaluating virulence and implementing disease control measures. Skin samples obtained from afflicted cattle serve as the primary source for LSDV isolation due to its tropism for epidermal cells. Other tissues, including blood, lung, spleen, and saliva samples, are also employed for viral isolation. This chapter presents protocols for the convenient isolation of LSDV, relying on the plaque formation phenotype and utilizing MDBK cells. Emphasis is placed on stringent quality control methodologies to identify isolated viruses through multiple techniques, facilitating further investigations such as the in vitro growth of isolated LSDV.

Lumpy skin disease: a systematic review of mode of transmission, risk of emergence, and risk entry pathways.

Lumpy skin disease (LSD), a viral disease of cattle, can be acute, subacute, or inactive. It is distinguished by fever and the abrupt emergence of firm, confined cutaneous nodules that usually necrotize. Similar lesions may occur in the skeletal muscles and the mucosae of the digestive and respiratory tracts. It is an enzootic, rapidly explorative, and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. LSDV has a large genome, it is employed as a vaccine carrier, generating a new complex with other viral genes by homologous recombination. This review summarizes our current knowledge of lumpy skin disease (LSD), its impact on animal health, host-pathogen interaction, etiology, signs or symptoms, prevention, and treatment strategies.

Carcinoma buccal mucosa with cutaneous metastasis: An unusual presentation

Head-and-neck cancer is a common cancer in India. Oral cavity cancer accounts for 50% of all head and neck sites. The most common sites of distant metastasis are the lung, liver, and bone. The incidence of cutaneous metastasis is a very rare site. We report a case of early-stage carcinoma buccal mucosa post-surgery and adjuvant radiotherapy developed skin metastasis shortly after completion of treatment. A 37-year-old female non-smoker, non-alcoholic diagnosed with early-stage carcinoma right buccal mucosa cT1N0M0. She underwent surgery of wide local excision with marginal mandibulectomy and extended supra-omohyoid neck dissection. In post-surgery, the histopathological report was moderately differentiated squamous cell carcinoma, pT2N1Mx. She completed her adjuvant radiotherapy 59.4Gy/33 fractions with six cycles of concurrent chemotherapy cisplatin 40 mg/m2. She developed difficulty in swallowing, increased oral secretions, and thickening over right-sided scar marks shortly after 10 weeks of completion of treatment. Rapidly, she developed multiple cutaneous nodules over both sides of the entire face and neck. Dermal biopsy reveals metastatic squamous cell carcinoma. Skin metastasis from head-and-neck malignancy is an uncommon entity and in the early stage, it is very rare. Initially, it is difficult to diagnose as it looks like some disseminated bacterial or fungal infection but we should always keep in mind this entity as cancer can metastasize and present in any atypical forms.

Phaeohyphomycosis caused by Trematosphaeria grisea in an immunocompromised English springer spaniel

AbstractA 10‐year‐old, male, farm‐based springer spaniel that presented with subacute progressive left‐sided central vestibular signs was diagnosed with meningoencephalitis of unknown origin. The patient received prednisolone (2 mg/kg/day orally), ciclosporin (5 mg/kg orally twice a day) and a single infusion of cytarabine (200 mg/m2). Six weeks later, neurological signs had resolved, but multiple cutaneous nodules developed on the limbs, trunk and face. Lesions discharged a dark purulent material without tissue grains. A ‘filamentous fungus’ was isolated, but discarded without identification. Aspirates from nodules showed pigmented, septate fungal hyphae, and culture of aspirates yielded Trematosphaeria grisea. Itraconazole (5 mg/kg once a day) and gradual tapering of immunosuppressive drugs led to resolution of nodular lesions over 4 months without neurological relapse. A fungal granuloma developed transiently 8 months after starting itraconazole. Immunosuppressive drugs were stopped 15 months after introduction without neurological relapse. Itraconazole was withdrawn 8 weeks later, 5 months after last relapse of skin disease.

A Rare Case of Mycosis Fungoides of the Scalp Treated With Electron-Beam Radiation Therapy

Abstract Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma comprising 44% of cutaneous lymphomas and accounting for less than 1% of non-Hodgkin lymphomas. It is clinically characterized by a focal or diffuse cutaneous patch, plaque, and tumor nodules, and is difficult to diagnose in the early stages because the symptoms and skin biopsy findings are similar to those of other skin conditions such as psoriasis, eczema, and lichenoid dermatoses. Here, we present a case about a patient who presented with a focal nodular skin lesion over the scalp.

Scrotal calcinosis cutis an unrelated finding in benign prostatic hyperplasia patient, is treatment sine qua non? A case report

Calcinosis cutis is a reactive and nonmalignant lesion characterized by solitary or multiple cutaneous nodules that can affect different parts of the body including the scrotum among other structures. Treatment is often sought because of cosmesis, itching, or pain. Despite this, it remains unclear or unimaginable why patients will be reluctant to accept treatment in the face of disfigurement. Several reasons have been documented, but the fear of genital mutilation from open surgical intervention is an unfamiliar reason advanced by the index case for declining open surgical intervention. Its diagnosis requires careful clinical evaluation and is confirmed by lesional biopsy for histological confirmation. This is a case of a 50-year-old trader who presented to our facility with a 35-year history of multiple, painless scrotal nodules and difficulty in passing urine for six months’ duration. He was diagnosed with benign prostatic hyperplasia (BPH) with the indication for surgical therapy and idiopathic scrotal calcinosis cutis. He consented and had endoscopic therapy for benign prostatic hyperplasia (BPH) but was reluctant to open surgical intervention for idiopathic scrotal calcinosis cutis despite disfigurement because of the fear of genital mutilation. The current treatment options include follow-up observation, medications, cryotherapy, laser, and surgical excision, depending on the patient’s choice, availability, and surgical expertise. The surgical option is often favored and encouraged due to its associated reduced chances of recurrence. Therefore, it is pertinent to respect the patient’s opinion and should override other considerations in clinical practice. The lesson herein can assist other clinicians in avoiding justifiable medical litigations, hence, the need for this case report and a review of the literature.

Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice.MethodsInvestigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain.DiscussionData from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention.Trial registrationclinicaltrials.gov NCT05855109 (submission date: 3 May 2023).

Juvenile Xanthogranulomatosis in a Hemophilic Boy: Case Report

Juvenile Xanthogranulomatosis (JXG) is a condition, characterized by a proliferation of histiocytes, primarily observed in infants and young children. Cutaneous manifestations appear as yellow-orange-brown papules or nodules, typically localized on the face, neck, and upper chest. While most lesions regress spontaneously, some may require intervention for aesthetic, diagnostic, or hemorrhagic reasons. A rare case of disseminated JXG in a child with hemophilia has been reported. In this patient with severe hemophilia A, cutaneous nodules appeared, some associated with bleeding requiring appropriate management. Treatment included the administration of factor VIII to prevent bleeding during surgical procedures and secondary prophylaxis, to control recurrent bleeding. The outcome was favorable with the disappearance of the cutaneous lesions without sequelae, under regular surveillance for both medical conditions. This case highlights the rare association between juvenile xanthogranulomatosis (JXG) and hemophilia, a combination that has never been documented in the medical literature. This association only impacts the management of JXG when the cutaneous lesions bleed and their excision becomes necessary.

Posaconazole followed by combination itraconazole and terbinafine for treatment of disseminated histoplasmosis in a cat.

This is the first reported use of posaconazole for the treatment of feline disseminated histoplasmosis. Approximately 1-year-old female spayed domestic longhair cat. The cat presented to our institution with weight loss, lymphadenomegaly, hepatosplenomegaly, limb edema, abdominal fluid distension and ulcerated cutaneous nodules. The cat had been previously diagnosed with disseminated histoplasmosis at another institution approximately 6 months prior. Clinical signs had been refractory to treatment with fluconazole. Itraconazole had next been tried, and the cat's weight continued to decline, lesions failed to regress, and the cat formed abdominal fluid distension and marked pelvic limb edema. The cat was prescribed posaconazole along with prednisolone. The cat's demeanor, body weight, and lesions all markedly improved. Histoplasma antigen was undetectable in urine samples while the cat was receiving posaconazole. However, posaconazole blood levels paired with markedly elevated ALT suggested potential toxicity and the drug was discontinued. Upon cessation of posaconazole, the cat's lesions returned with cytologic evidence of intralesional Histoplasma yeast. Itraconazole combine with terbinafine was prescribed. At last follow-up, the cat was clinically well, off all anti-fungal medication, and without detectable Histoplasma antigen in the urine. Posaconazole therapy showed promise in this case. Had a safe and therapeutic dose been arrived at, we suspect that posaconazole would have cleared or maintained clinical remission of this cat's disease. This is the first report using posaconazole and the first successful report using combination itraconazole and terbinafine for the treatment of feline disseminated histoplasmosis. Generic drugs were used throughout this case report; the drug manufacturers are unknown to the authors.

Pediatric Orbital Juvenile Xanthogranuloma: A Case Series and Review of the Literature.

Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as a single self-limiting cutaneous nodule in the pediatric population. Orbital JXG is extremely rare, and its clinical course and management are not well understood or defined. Herein we present 3 cases of orbital JXG and provide a detailed literature review. Review of 3 cases with orbital JXG and literature review of all published cases. Three presented cases demonstrate the heterogeneous clinical course of orbital JXG. Although centred around the use of steroids, there is neither robust evidence nor consensus on its management. The wider JXG literature is currently concentrated around the classification of JXG with respect to histiocytosis, especially the exclusion of extracutaneous JXG as separate diseases. This separation is based on clinical, histopathological, and molecular findings. It is unclear where orbital JXG best fits in this emerging classification of JXG. Our review of the cases and literature on orbital JXG show that it may manifest with variable clinical course and its molecular pathogenic mechanism may be different to that of the cutaneous JXG.

Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

Susceptibility of Mediterranean Buffalo (Bubalus bubalis) following Experimental Infection with Lumpy Skin Disease Virus.

Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever, and lymphadenitis. LSD is endemic in Africa and the Middle East but has spread to different Asian countries in recent years. The disease is well characterized in cattle while little is known about the disease in buffaloes in which no experimental studies have been conducted. Six buffaloes and two cattle were inoculated with an Albanian LSD virus (LSDV) field strain and clinically monitored for 42 days. Only two buffaloes showed fever, skin nodules, and lymphadenitis. All samples collected (blood, swabs, biopsies, and organs) were tested in real-time PCR and were negative. Between day 39 and day 42 after inoculation, anti-LSDV antibodies were detected in three buffaloes by ELISA, but all sera were negative by virus neutralization test (VNT). Cattle showed severe clinical signs, viremia, virus shedding proven by positive real-time PCR results, and seroconversion confirmed by both ELISA and VNT. Clinical findings suggest that susceptibility in buffaloes is limited compared to in cattle once experimentally infected with LSDV. Virological results support the hypothesis of buffalo resistance to LSD and its role as an accidental non-adapted host. This study highlights that the sensitivity of ELISA and VNT may differ between animal species and further studies are needed to investigate the epidemiological role of water buffalo.