6/12/2018 Infectious Dermatopathology – What is “bugging” you? Alina G. Bridges, D.O. Associate Professor Program Director, Dermatopathology Fellowship ASDP Alternate Advisor to the AMA-RUC Department of Dermatology, Division of Dermatopathology and Cutaneous Immunopathology Mayo Clinic, Rochester Disclosures ▪Relevant Financial Relationships ▪None ▪Off Label Usage ▪No Background ▪ One of the most challenging tasks in medicine is the accurate and timely diagnosis of infectious diseases ▪ Classically, infectious disease diagnosis is under the domain of the microbiology laboratory ▪ Culture ▪ May not be performed due to lack of clinical suspicion ▪ Time consuming ▪ Not possible for some organisms ▪ May fail to grow organism due to prior antibiotic treatment, sampling error 1 6/12/2018 Background, continued ▪ Infectious diseases has always played a significant role in our specialty ▪ Many infectious diseases have primary skin manifestations ▪ Dermatopathologists offer invaluable information: ▪ Knowledge of inflammatory patterns and other similar appearing non-infectious conditions ▪ Visualize microorganisms and associated cellular background ▪ Colonization versus Invasion Course Objectives At the end of this course, participants should be able to: ▪ Identify common and important infectious organisms in dermatopathology specimens based on histopathologic features ▪ Develop an appropriate differential diagnosis based on morphologic features, clinical presentation, exposure history, and corresponding microbiology results ▪ Use an algorithm to differentiate infectious processes from inflammatory processes and morphologic mimickers ▪ Select and interpret appropriate special stains and ancillary tests to facilitate or support the morphologic diagnosis 5 Histologic patterns of importance in the diagnosis of cutaneous infections ▪ Pattern recognition ▪ Morphology of the organisms ▪ Correlate with culture ▪ Serology ▪ Molecular testing 2 6/12/2018 Histologic patterns of importance in the diagnosis of cutaneous infections ▪Invisible dermatoses Invisible Dermatoses ▪Dermatophyte (tinea) infection ▪Tinea versicolor ▪Tinea nigra ▪Pitted keratolysis ▪Erythrasma ▪Erythema migrans Dermatophyte (tinea) infection Caused by Trichophyton, Epidermophyton, and Microsporum genera 3 6/12/2018 Clue for dermatophyte infection: “Sandwich” sign Tinea versicolor Caused by the Malassezia globose > Malassezia furfur Tinea nigra Superficial mycosis caused by the dematiaceous fungus Hortaea werneckii 4 6/12/2018 Pitted keratolysis Caused by several bacterial species, including Corynebacteria, Dermatophilus congolensis, Kytococcus sedentarius, Actinomyces and Streptomyces Erythrasma Superficial infection caused by Gram positive bacillus, Corynebacterium minustissimum Erythema migrans Caused by tick-borne spirochete B. Burgdorferi 5 6/12/2018 Histologic patterns of importance in the diagnosis of cutaneous infections ▪Invisible dermatoses ▪Infectious bulla and vesiculopustule Infectious Bulla Intraepidermal ▪ Acantholytic ▪ Subcorneal – SSSS ▪ Subcorneal pustule – Impetigo ▪ Spongiform pustule – Candidiasis ▪ Spongiotic ▪ Dermatophyte ▪ Eosinophilic spongiosis ▪ Insect bite reaction ▪ Ballooning degeneration ▪ HSV, VZV ▪ Hand-foot-mouth disease Subcorneal bulla - Staphylococcal scalded skin syndrome (SSSS) 6 6/12/2018 Subcorneal pustule- Bullous Impetigo Spongiform pustule - Candidiasis Candidiasis 7 6/12/2018 Spongiotic intraepidermal bulla - Dermatophyte (tinea) Eosinophilic spongiosis -Insect bite reaction 8 6/12/2018 Ballooning and reticular degeneration - Herpes Virus Infection Kaposi’s Varicelliform Eruption (Eczema Herpeticum) HSV and Darier’s disease P. vulgaris and HSV 9 6/12/2018 Oral biopsy with Oral biopsyBOTH with CMV BOTH & HSV CMV & HSV CMV HSV The Many Faces of The Many Faces of Human Herpesviridae EBV ISH Summary: Clinically important herpesviruses Name HHV-1 Herpes simplex virus 1 HHV-2 Herpes simplex virus 2 HHV-3 Varicella zoster virus HHV-4 Epstein-Barr virus HHV-5 Cytomegalovirus HHV-6A&B Roseoloviruses HHV-7 HHV-8 Kaposi-sarcoma-associated herpesvirus 10 6/12/2018 HHV-6 and HHV-7 associated diseases ▪ Pityriasis rosea • Graft-versus-host disease • Gianotti-Crosti syndrome ▪ DRESS • Exanthem subitem- roseola ▪ Lichen planus • Increased susceptibility to BCC Acantholytic SCC vs. Herpetic infection Bullous Grover Disease vs. Herpetic infection ▪ Avoid pitfall by: ▪ Absence of true cytopathic effect ▪ Recognition of dyskeratosis ▪ Focality of process 11 6/12/2018 Ballooning degeneration - Hand-Foot-Mouth Disease, Coxsackie A16 Molluscum Contagiosum, Pox virus HPV - Verruca 12 6/12/2018 HPV-Epidermodysplasia verruciformis Histologic patterns of importance in the diagnosis of cutaneous infections ▪Invisible dermatoses ▪Infectious bulla and vesiculopustule ▪Infectious suppurative folliculitis Suppurative Folliculitis Pseudomonas folliculitis (necrosis, abscess, neutrophils) ▪ Infectious ▪ Bacterial ▪ Viral – Herpes ▪ Fungal ▪ Dermatophyte ▪ Pityrosporum 13 6/12/2018 Bacterial folliculitis Erysipelas – Group A Streptococci Deep abscess Cellulitis Actinomycosis 14 6/12/2018 HSV Folliculitis Polyoma Virus-associated Trichodysplasia Spinulosa Majocchi’s granuloma 15 6/12/2018 Pityrosporum folliculitis Histologic patterns of importance in the diagnosis of cutaneous infections ▪Invisible dermatoses ▪Infectious bulla and vesiculopustules ▪Infectious suppurative folliculitis ▪Lichenoid +/- granulomatous inflammation Lichenoid interface dermatitis Syphilis 16 6/12/2018 Lichenoid and granulomatous dermatitis Lichenoid and granulomatous dermatitis Diagnosis: Histoplasma capsulatum ▪Distinguishing Features: ▪ Differential diagnosis of ▪ 2-4 µm yeast parasitized histiocytes ▪ Single narrow-based ▪ Leishmaniasis budding ▪ Rhinoscleroma ▪ Often inside histiocytes ▪ Granuloma inguinale ▪ Virtually invisible on ▪ Penicillium marneffei H&E ▪ Lepromatous leprosy 17 6/12/2018 Leishmaniasis – History helpful; parasitized histiocytes with 2-4 m nonencapsulated round/oval bodies containing a nucleus & paranucleus (kinetoplast); stain with Giemsa Rhinoscleroma - 2-3 m Gram-negative bacilli (Frisch bacilli; Klebsiella rhinoscleromatis) in Mikulicz cells (larger than the other parasitized histiocytes); plasma cells & Russell bodies prominent Granuloma inguinale - Parasitized histiocytes with 1-2 m encapsulated Gram-negative bacilli (Donovan bodies; Klebsiella granulomatis); stain with Giemsa 18 6/12/2018 Penicillium marneffei - Parasitized histiocytes with 1-8 m pleomorphic round to sausage shaped yeast; unlike histoplasmosis, divides by binary fission not by budding Lepromatous Leprosy Histologic patterns of importance in the diagnosis of cutaneous infections ▪Invisible dermatoses ▪Infectious bulla and vesiculopustules ▪Infectious suppurative folliculitis ▪Lichenoid +/- granulomatous inflammation ▪Pseudoepitheliomatous hyperplasia with intraepithelial microabscesses 19 6/12/2018 Pseudoepitheliomatous hyperplasia with intraepithelial microabscesses ▪ Deep fungal infections ▪Halogenoderma ▪ Blastomycosis-like ▪Pemphigus vegetans pyoderma ▪Pyostomatitis ▪ Atypical mycobacterial vegetans infections ▪ Protothecosis ▪ Leishmaniasis Blastomycosis dermatitidis • Cryptococcus neoformans ▪ Broad-based budding ▪ Narrow-based budding ▪ Uniform large (8-15 ▪ Variable size (4 - 20 µm) micron) diameter ▪ Polysaccharide capsule (large halo on H&E) ▪ Always a yeast, not dimorphic 20 6/12/2018 Histologic patterns of importance in the diagnosis of cutaneous infections ▪ Invisible dermatoses ▪ Infectious bulla – intraepidermal ▪ Suppurative folliculitis ▪ Lichenoid +/- granulomatous inflammation ▪ Pseudoepitheliomatous hyperplasia with intraepithelial microabscesses ▪ Suppurative granuloma Suppurative granuloma ▪ Deep fungal infections ▪ Atypical mycobacterial infections ▪ Sporotrichosis ▪ Tularemia ▪ Cat-scratch disease Suppurative granulomas: Chromomycosis 21 6/12/2018 Suppurative granulomas: Chromomycosis ▪ Small, 6-12 m, round, ▪ Chronic verrucous disease thick-walled, brown spores caused by several (Medlar bodies, copper dematiaceous fungi pennies, sclerotic bodies) ▪ Fonsecaea pedrosoi – within giant cells or free in most common ▪ dermis Fonsecaea compacta ▪ Phialophora verrucosa ▪ Cladosporium carrionii Suppurative granulomas: Atypical Mycobacterial Infections QUIZ ▪59 yo woman admitted with 1 yr. history of expanding leg ulcers ▪On prednisone, cyclosporine and azathioprine for presumed diagnosis of pyoderma gangrenosum ▪No biopsy 22 6/12/2018 What is your diagnosis? A. Pyoderma gangrenosum B. Lymphoma C. Infection D. Occlusive vasculopathy E. Calciphylaxis 23 6/12/2018 Sporotrichosis Yeast form: round (6 - 8 um) or cigar-shaped (diagnostic of sporotrichosis) Sporotrichosis Admission 4 months 1 year Paracoccidiomycosis Yeast: 4 to 60 μm Clear space around fungus Usually found inside multinucleated giant cells Pilot wheel: Pathognomonic -Multiple buds surrounding the parent cell Not all yeasts show buds around the entire circumference -May be confused with sporothrix or crypto 24 6/12/2018 Histologic patterns of importance in the diagnosis of cutaneous infections ▪ Invisible dermatoses ▪ Infectious bulla – intraepidermal ▪ Suppurative folliculitis ▪ Lichenoid +/- granulomatous inflammation ▪ Pseudoepitheliomatous hyperplasia with intraepithelial microabscesses ▪ Suppurative granuloma ▪ Tuberculoid granuloma Tuberculoid granuloma: Tuberculosis; Lupus vulgaris Histologic patterns of importance in the diagnosis of cutaneous infections ▪ Invisible dermatoses ▪ Infectious bulla – intraepidermal