Unusual isolated cytomegalovirus cutaneous infections: A subtle histopathologic diagnosis with review of the literature.

Cytomegalovirus (CMV) infection is common and often self-limited. Reactivation results in a variety of disease presentations, especially in the setting of immunocompromise. While cutaneous manifestations of systemic CMV infection are rare, dermatologic manifestations of CMV are increasingly reported with a wide morphologic spectrum clinically. Three male patients, with untreated human immunodeficiency virus (HIV), penile lichenoid dermatitis treated with long-term topical and intralesional corticosteroids, and metastatic Merkel cell carcinoma on immune checkpoint inhibitor therapy, each presented with isolated cutaneous ulcers. The ulcers were located on the perianal skin, glans of the penis, and distal thumb. In each case, nonspecific histopathologic features were seen. However, very rare dermal cytomegalic cells with nuclear and cytoplasmic inclusions were present and highlighted with an immunohistochemical stain for CMV. Isolated ulcers due to CMV infection may occur in the setting of systemic or localized immunosuppression. A high index of suspicion is needed upon histopathologic evaluation, as few cytomegalic cells may be present and accurate diagnosis is crucial for prompt and appropriate clinical management.

Scrotal ulcers in an infant with multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection.

The majority of cases of multisystem inflammatory syndrome in children (MIS-C) manifest non-specific mucocutaneous features. We report the case of a 3-month-old infant presenting with purpura, acral desquamation, and scrotal ulcers. Scrotal ulcers have not been previously reported in MIS-C and add to the spectrum of cutaneous findings associated with the disorder.

Eruptions and related clinical course among 296 hospitalized adults with confirmed COVID-19.

BACKGROUND: Limited information exists on mucocutaneous disease and its relation to course of COVID-19. OBJECTIVE: To estimate prevalence of mucocutaneous findings, characterize morphologic patterns, and describe relationship to course in hospitalized adults with COVID-19. METHODS: Prospective cohort study at 2 tertiary hospitals (Northwell Health) between May 11, 2020 and June 15, 2020. RESULTS: Among 296 hospitalized adults with COVID-19, 35 (11.8%) had at least 1 disease-related eruption. Patterns included ulcer (13/35, 37.1%), purpura (9/35, 25.7%), necrosis (5/35, 14.3%), nonspecific erythema (4/35, 11.4%), morbilliform eruption (4/35, 11.4%), pernio-like lesions (4/35, 11.4%), and vesicles (1/35, 2.9%). Patterns also showed anatomic site specificity. A greater proportion of patients with mucocutaneous findings used mechanical ventilation (61% vs 30%), used vasopressors (77% vs 33%), initiated dialysis (31% vs 9%), had thrombosis (17% vs 11%), and had in-hospital mortality (34% vs 12%) compared with those without mucocutaneous findings. Patients with mucocutaneous disease were more likely to use mechanical ventilation (adjusted prevalence ratio, 1.98; 95% confidence interval, 1.37-2.86); P < .001). Differences for other outcomes were attenuated after covariate adjustment and did not reach statistical significance. LIMITATIONS: Skin biopsies were not performed. CONCLUSIONS: Distinct mucocutaneous patterns were identified in hospitalized adults with COVID-19. Mucocutaneous disease may be linked to more severe clinical course.

Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

Cutaneous Lymphoproliferative Disorders: What's New in the Revised 4th Edition of the World Health Organization (WHO) Classification of Lymphoid Neoplasms.

Cutaneous lymphoproliferative disorders remain a challenging aspect of dermatopathology, in part due to the rarity of the entities and extreme variability in clinical outcomes. Although many of the entities remain unchanged, the approach to some of them has changed in the new 2016 classification scheme of the World Health Organization. Chief among these are Epstein-Barr virus-associated lymphoproliferative disorders such as Epstein-Barr virus-associated mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and breast implant-associated anaplastic large cell lymphoma. In addition, translocations and gene rearrangements such as those involving the 6p25.3 locus have started to inform diagnosis and classification of anaplastic large cell lymphoma and lymphomatoid papulosis. In this review, we will examine what is new in the diagnostic toolbox of cutaneous lymphoproliferative disorders.

Cutaneous Cytomegalovirus Infection in an Immunocompetent Patient: Innocent Bystander or Culprit?

We present a rare case of cutaneous cytomegalovirus (CMV) infection in a nonimmunocompromised patient. A 74-year-old woman with a history of diabetes presented with an ulcer on the right lateral tibia that occurred at the site of a nerve core biopsy. Subsequent biopsy of the ulcer edge showed granulation tissue with neutrophilic inflammation. The patient underwent extensive antibiotic treatment for possible infection with weekly wound care. However, the ulceration persisted and enlarged. A repeat biopsy 1 year later showed superficial and deep mixed inflammation with an associated vasculitis. On close examination, endothelial and eccrine ducts cells showed characteristic CMV viral cytopathic changes with positivity on CMV immunohistochemical stain. Although the patient was started on valganciclovir, the ulceration did not resolve with treatment and slightly enlarged. Treatment modalities included dapsone, prednisone, weekly wound care, wound vacuum, and eventually a skin graft of the ulcer site. This case highlights the presence of CMV infection in a cutaneous ulceration in a relatively immunocompetent patient, and the lack of response to treatment raises the question whether CMV was causative, partially contributory, or simply an innocent bystander.

Feline herpesvirus ulcerative dermatitis: an atypical case?

BACKGROUND: Feline herpesvirus ulcerative dermatitis is an uncommon skin disease in cats, with a predominantly facial distribution characterized by massive infiltration of eosinophils and, occasionally, predominant neutrophils. OBJECTIVE: To describe the clinical and histopathological features of a putative atypical case of feline herpesvirus dermatitis. ANIMAL: A 10-month-old, intact male, European cat was presented with chronic monolateral ulcerative dermatitis with adherent crusts on the left pinna. The lesion had been present for six months and worsened after the administration of corticosteroids. METHODS: Clinical and histopathological examination, immunohistochemistry, nested PCR and transmission electron microscopy (TEM). RESULTS: Histological examination of skin biopsies showed multifocal ulcerative and necrotic lesions, involving the superficial and deep dermis covered by thick haemorrhagic and serocellular crusts. The superficial, medium and deep dermis was heavily infiltrated with mast cells and plasma cells, with a lower number of neutrophils and eosinophils. In the nuclei of some cells in the deep dermis, whose histotype was unrecognizable with routine haematoxylin and eosin stain, intranuclear eosinophilic inclusion bodies were noticed. Nested PCR and TEM supported the hypothesis of FeHV-1-induced dermatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: This case is noteworthy for the infrequent location on the pinna and the atypical histopathological features of the lesion, with a predominant infiltration of mast cells and plasma cells. Our findings suggest that herpesvirus dermatitis should be listed as a differential diagnosis in case of ulcerative dermatitis when the location and histological features are atypical.

Epstein-Barr Virus-associated Mucocutaneous Ulcer in a Patient With T-Cell Acute Lymphoblastic Leukemia: Importance of Accurate Diagnosis and Conservative Management.

Epstein-Barr virus-associated mucocutaneous ulcer (EBV-MCU) is a recently characterized entity that falls under the spectrum of EBV-lymphoproliferative disorders. First described in 2010 by Dojcinov et al, it is an EBV-driven localized proliferation of B cells, occurring in mucocutaneous tissues including the skin, the oropharynx, and the gastrointestinal tract of immunosuppressed patients in the absence of an intact T-cell repertoire. Typically, it has been described in elderly patients with age-related immunosenescence and patients who are on immunosuppressive therapy. However, only 2 cases have been reported in pediatric, adolescent, and young adult age groups, with all these patients manifesting after solid organ transplant. To the best of our knowledge there are no case reports of EBV-MCU occurring in association with hematologic malignancy. Here, we present a case of EBV-MCU in a young adult patient with T-cell acute lymphoblastic leukemia. Our report serves to promote awareness among clinicians regarding this newly described and extremely rare clinical entity in young immunosuppressed patients. In addition, we highlight the importance of accurate diagnosis to prevent overtreatment of this indolent, often self-resolving disease that has a significant clinicopathologic overlap with other aggressive forms of EBV-lymphoproliferative disorders that require more intensive therapy.

Cytomegalovirus Scrotal Ulcer in a Renal Transplant Patient.

BACKGROUND: Cytomegalovirus (CMV) is a highly prevalent herpesvirus that can present with cutaneous disease in immunocompromised individuals. This may reflect systemic involvement, which is associated with significant morbidity and mortality. OBJECTIVE: To report a case of cutaneous CMV in an immunocompromised patient and to discuss the differential diagnosis of genital ulcers. METHODS: A medical chart review was conducted on a patient who presented with a scrotal ulcer after renal transplantation. A review of the literature on cutaneous CMV disease was also completed. RESULTS: Biopsy of the scrotal ulcer revealed classic findings of CMV disease. The patient also developed CMV viremia. Treatment with valganciclovir resolved his scrotal ulcer and viremia. CONCLUSION: The differential diagnosis for genital ulcers is broad, especially in the immunocompromised patient. Cutaneous CMV disease should be ruled out with biopsy and immunohistochemical examination in immunocompromised patients, as it may reflect systemic involvement and significantly affect patient care.

A 7-week-old Nepali girl with a perianal ulcer: brief report.

Cytomegalovirus (CMV) can rarely present with skin findings. Cutaneous CMV is most often found in patients who are immunocompromised because of acquired immunodeficiency syndrome, lymphoma, or other conditions. We present a rare case of an immunocompetent 7-week-old girl with a perianal ulcer attributed to CMV.

A rare case of trigeminal trophic syndrome with periorbital cellulitis and full-thickness upper eyelid defect in an undiagnosed patient with human immunodeficiency virus: a case report.

BACKGROUND: Trigeminal trophic syndrome is a rare cranial and facial condition caused by damage to the central or peripheral branches of the trigeminal nerve. This syndrome consists of a triad of anesthesia, paresthesia, and crescent-shaped facial ulcer involving the ala nasi and sometimes extending to the upper lip. Although previous screening for human immunodeficiency virus in some patients with trigeminal trophic syndrome was negative, we present a unique case of trigeminal trophic syndrome who tested positive for human immunodeficiency virus with eye complications. CASE PRESENTATION: We present a rare case of trigeminal trophic syndrome in a 44-year-old Black African woman who tested positive for human immunodeficiency virus. She presented with a 6-week history of progressive, persistent, and painless left sided facial and scalp ulcerations that started as small skin erosion. Diagnosis of trigeminal trophic syndrome was made on clinical grounds based on the triad of anesthesia, paresthesia, and unilateral crescent-shaped ulcer in the trigeminal dermatome and her past medical history. The ulcer healed completely after counseling and pharmacological therapy, but she later developed left periorbital cellulitis and left upper eyelid full-thickness defect. CONCLUSION: This is by far the first documented case of trigeminal trophic syndrome with a positive human immunodeficiency virus test. Testing for human immunodeficiency virus in patients with trigeminal trophic syndrome is necessary as this can help improve clinical management and treatment outcomes. Seeking the services of specialists remotely in resource constraint settings is beneficial for managing complications associated with trigeminal trophic syndrome.

Varicella precipitating febrile ulceronecrotic Mucha-Habermann disease.

We report a 9-year-old boy with skin lesions clinically and histologically compatible with pityriasis lichenoides et varioliformis acuta that evolved to the severe variant febrile ulceronecrotic Mucha-Habermann disease and finally to pityriasis lichenoides chronica. Varicella-zoster virus (VZV) was isolated in culture medium from the skin lesions and serum serology was positive for VZV. This is the first time that a virus has been isolated in culture in this condition.

[Lymphadenopathy: demarcation to malignant lymphomas]. / Lymphadenopathie: Grenzziehung zu malignen Lymphomen.

Recognition of the differential diagnosis between lymphadenitis and malignant lymphoma requires good knowledge of the basic forms of the disease as well in depth knowledge of the structure of the individual compartments. There are defined forms of lymphadenitis where the differential diagnosis to certain lymphoma entities is known. Other reactive structural alterations show indistinct limits so that a decision is only possible after using additional techniques, such as immunohistochemistry and molecular analyses. Finally, there are marginal areas which can only be clarified by including clinical data.