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  • On Imuran and systemic corticosteroids
  • Erythematous Nodules on left dorsal hand and left wrist (almost sporotrichoid)
  • Central crusting
  • Punch biopsy was obtaned from dorsal wrist as well as tissue for culture for bacterial, fungal and acid fast bacilli
  • Ulceration with dense inflammation in the dermis
  • Suppurative and fibrinopurulent inflammation and hemorrhage centrally
  • Start to see larger cells and unusual intracytoplasmic sturctures on higher power
  • Characteristic morula or soccer ball forms
  • Characteristic thick walled organisms here with spores forming morula forms (“soccerball” or mulberry forms
  • Pas stain highlights these organisms
  • Soccer ball or mulberry forms
  • On Imuran and systemic corticosteroids
  • Large area of cellulitis with Centrally Necrotic and purpuric eschar
  • Eschar with edema and necrosis
  • Punch biopsy showing hemorrhage and inflammation with some overlying epidermal ulceration
  • Areas of suppuration
  • Thick walled organsims with non septate on pas stain
  • Right angle branching
  • Broad non septate hyphae (often ribbon like)
  • Soccer ball or mulberry forms
  • Broader hyphae with more collapsed and twisted look Unlike aspergillus which are narrower with septations and acute angle branching
  • PE: Multiple ulcerated coalescing plaques with yellowish-brown crust and surrounding erythema right leg
  • Notice how some lesions had a yellow exudate while others more black brown
  • Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli) r/o infectious vs carcinoma vs stasis ulcer Overlying ulceration with superficila inflammation as well as a deeper focus of inflammation
  • Focusing on the superficial ulcer
  • Coating of fibrinopurulent material
  • Numerous fungal organisms- almost two morphologies present Small slender organisms Larger yeast and hyphal forms
  • Deeper focus
  • Larger oval organsims with septations
  • Organisms stain here with gMs silver stain
  • Larger organisms here with oval morphology
  • Smaller narrower organisms
  • Deeper focus here are larger organisms
  • 2 organisms cultured 1 creamy white colonies 1 pigmented dark black colonies Note similarity to patients clinical lesions
  • Mycelia and conidia
  • Hand grenades Consistent with alternaria species
  • Solitary or grouped crusted papules and plaques Subcutaneous nodules Vegetating tumors Multiple ulcerations
  • 10- 15 um (wider than aspergillus and fusarium) but less than mucormycosis (6 to 50 um) Relatively little branching, occasional acute angle branching
  • widespread molluscum like lesions with fever
  • Some follicularly based
  • Widespread over trunk
  • Umbilicated papules (molluscoid)
  • Dermatology consult called to evaluate and cutaneous lesions Skin biopsy was performed and portions sent for bacterial, mycobacterial, and fungal culture Patient begun on broad spectrum antibiotics and antifungals (IV Amphotericin B) Patient consented for HIV test Dense nodular infiltrate throughout the dermis
  • Suppuration and granulomatous inflammation
  • Parasitized histiocytes
  • There are numerous PAS positive organisms within histiocytes and freely within dermis
  • Dimorphic fungus At 37 ˚ C, Colony grows as yeast which reproduces by fission (helps to differentiate from H. capsulatum ) At 25 ˚ C, Colonies on Sabouraud agar usually velvety gray to white with radial folds (inhibited by cycloheximide) Culture often develops yellow-green to brown areas with characteristic diffusing red pigment Conidia resemble “skeleton hands” or “broomsticks” microscopically
  • Yeast forms budding by septation at 37 C
  • Conidia with broomstick appearance or skeleton hands
  • Patient’s culture confirmed diagnosis of disseminated penicilliosis Patient’s symptoms and skin lesions resolved quickly with antifungal therapy in two weeks Patient remained on maintenance itraconazole and was also begun on HAART
  • Penicillium chrysogenum used to produce the antibiotic penicillin Fleming discovered penicillium
  • P. marneffei has a restricted geographical distribution as seen in other dimorphic fungi such as Coccidioides , Paracoccidioides , and Blastomyces . Though the fungus was initially isolated from the bamboo rats and has also been recovered from internal organs of bamboo rats, the rodents are unlikely to be important in the transmission of the disease in nature and to humans. Penicilliosis marneffei has been classified as a geoanthromycosis: the fungus probably exists as a saprophyte in the environment (e.g. in the soil), and humans, as well as bamboo rats, are infected through inhalation of the conidiophores. This postulation, however, has not been proven beyond doubt A recent history of occupational or other forms of exposure to soil is also a significant risk factor. Importantly, exposure to or consumption of bamboo rats, was not a risk factor for infection. The exact mode of transmission of the fungus its natural habitat is still unsettled at the moment. The route of transmission and infection of P. marneffei is unknown at the moment. However, it is generally believed that inhalation of the conidia is a likely route, in line with the mode of infection for other moulds. The attachment of P. marneffei conidia to host cells and tissues is the first step in the establishment of an infection. The conidia-host interaction may occur via adhesion to the extracellular matrix protein laminin and fibronectin via a sialic acid-dependent process. Underlying immunosuppression can be found in 80% patients. The most frequent underlying disease is advanced HIV/AIDS Average CD4 count : 67 Infections in non-HIV-infected patients have been primarily among immunocompromised patients and less frequently in patients without any known underlying diseases.
  • Fever – nearly 100% patients Weight loss and anemia – 70% Pulmonary symptoms / cough – 50% Lymphadenopathy – 52% Hepatomegaly – 44% Splenomegaly – 23% Cutaneous lesions– 70% Mucocutaneous – 26% Predisposing factors besides AIDS: Alcoholism, TB, Hodgkin’s, immunosuppressive therapy, lymphoproliferative disorders, SLE, poor nutrition May occur rarely in immunocompetent patients May be localized or disseminated diseaseDisseminated disease: more common Similar to disease in AIDS patients Has been reported to occur even in immunocompetent patients Localized disease: rare Reported presentations: TB-like illness with cavitary pneumonia Solitary pulmonary nodules Osteomyelitis Superinfected lesions
  • Granulomatous Reticuloendothelial organs Immunocompetent Granulomas with yeast within histiocytes and multinucleated giant cells Suppurative Lung, subcutaneous tissue, and skin Immunocompetent Anergic Lung, liver, and skin Immunocompromised Necrotizing reaction with focal necrosis surrounded by diffuse infiltration of histiocytes engorged by proliferating yeast
  • The clinical and histologic picture was inconsistent with rhinoscleroma caused by a Klebsiella bacillus which usually causes a disfiguring nasopulmonary infection It was also inconsistent with granuloma inguinale which usually presents as a genital ulceration with exuberant granulation tissue This left the other four possibilities which were evaluated with special stains for AFB, Fungi, and Leishmania (Fite, Giemsa, and GMS) The special stains suggested a diagnosis of cutaneous peniciliosis which was also confirmed by the culture.
  • Histoplasmosis Difficult to grow with slow rate of growth Penicillium easily cultured with rapid rate of growth Yeast forms relatively indistinguishable at 37 c Mold forms at 25 C quite different Histoplasma Colonies on Sabouraud agar usually white (inhibited by cycloheximide) Culture often turns tan with age Penicillium Colonies on Saburaud agar usually velvety gray to white with radial folds (inhibited by cycloheximide) Culture often develops yellow-green to brown areas with characteristic diffusing red pigment
  • At 25 C mold forms – Thick walled round tuberculate conidia of histoplasma resemble “sea mines” microscopically Conidia of penicillium resemble “skeleton hands” or “broomsticks” microscopically
  • W/u for recent weight loss, fatigue , and anemia
  • Multiple discrete shiny papules with surrounding hyperpigmentation
  • Large eosinophilic deposits expanding the papillary dermis with a surrounding collarette
  • Evidence of surface irritation
  • Very pink and homogenous material
  • Admixture of inflammatory cells
  • Atypical hyperchromatic plasmacytoid cells
  • Congo Red and Crystal violet stains were negative Material strongly pas positive
  • Also positive for Kappa light chain immunohistochemical stain, negative for lambda
  • Strongly dif + for Igm
  • Transepidermal elimination, ulceration and crusting can occur Lipoid proteinoisis and epp usually not nodular deposits , usually around vessels and arranged perpendicular to epidermal surface Different ultrastructure
  • Bilateral malar areas – speckled blue black areas with slight erythema
  • Pigmented colloid milium
  • Pigmented colloid milium – caviar papules
  • Phenol used in leg ulcers Picric acid in burns Both now abandoned
  • 28-35 % of south african blacks
  • Groin with confluent round to gyrate pink to red plaques with exfoliative white-tan scale
  • Distal extermities also w/ erythematous circular plaques with erosion and scale
  • Confluent circular plaques
  • Lower extremities, more confluent erythema with fine scale
  • Peeling and fissuring of soles with tan-brown scale
  • Backs of extremities. –craquelee like exfoliative plaques with adherent tan-brown scale
  • Atrophic glossitis, fissuring angular cheilitis
  • Psoriasiform epidermal hyhperplasia
  • Psoriasiform hyperplasia with pallor and overlying confluent scale-crust
  • Pallor and vacuolization of upper epidermis with edema in superficial dermis
  • Vacuolization with parakeratotic scale-crust
  • Mixed infiltrate with neuts, eos in dermis.
  • Another biopsy showed more subtle findings with slight hyperplasia, spongiosis and areas of abrupt confluent parakeratosis
  • Abrupt parakeratosis
  • Another area with abrupt parakeratosis
  • Islet cell tumor – alpha cells - glucagon
  • Papular hyperpigmeted eruption with widespread induration
  • Indurated hyperpigmented areas on back
  • Leonine facies with supraorbital thickening
  • Fine
  • Donut sign
  • Nodular and diffuse process in dermis
  • Nodule in upper dermis
  • Associated fibrosis and interstitial mucin
  • Mucin stain shows marked deposits ofmucin within dermis
  • Multiple erythematous plaques on extremities
  • Yellowish hue
  • Also had xanthelasma like lesions periorbitally
  • Bilateral exudative and crusted ulcerative plaques radial aspect of both hands
  • Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli) Dense diffuse inflamamtory infiltrate with hemorrhage and overlying irregular hyperplasia
  • Dense infiltrae of neutrophils
  • No definitive vasculitis Special stains negative for afb, fungi, bacteria
  • Classical pG usually deepr ulcers with overhanging borders on lower extremities
  • PE: 10 x 9 cm slightly indurated square shaped hyperpigmented plaque with a 3 x 3 cm area of ulceration
  • First biopsy taken approximately 3 months after onset of lesion Submitted clinical data: r/o allergic contact, r/o fixed drug, r/o Lyme
  • Given the clinical history, the first biopsy was initially read as an interface dermatitis with features c/w a fixed drug eruption
  • Make note of how important a punch biopsy is. Second biopsy taken approximately 6 months later Submitted clinical data: fixed drug r/o other
  • Increased use of fluoroscopy guided interventional procedures since 1990’s Coronary artery stenting and angioplasty Transjugular intrahepatic portosystemic shunt placement (TIPS) Cardiac catheter ablation Chemotherapy catheter placement Percutaneous cholangiography Embolization procedures
  • Subsequent report in 1998 by Stone e t al described characteristic histologic features in patient who underwent coronary artery stenting under fluoroscopy Patient developed localized skin eruption on back at site of radiation approximately 7 days after procedure Oval to square shaped area of Erythema on left mid back with desquamation, painful Resembles fixed drug eruption clinically in early stages bx showed interface dermatitis Initial area of erythema became indurated and showed poikilodermatous changes clinically Subsequent biopsy seven months later showed changes of chronic radiation dermatitis
  • Immunohistochemical studies on the infiltrate T-lymphocytes Majority were CD8 (+) Lymphocytes infiltrating into epidermis also TIA-1 (+), a protein in cytotoxic lymphocytes and natural killer cells that triggers apoptosis in target cells Authors suggested that radiation may induce antigenic changes in keratinocytes leading to autoimmune attack by cytotoxic lymphocytes and subsequent apoptosis
  • FDA threshod absorbed dose in skin of 2 rad/min (0.02 Gy,min) and 20 rad/min (0.2 Gy/min) of areas of skin irradiated by a stationary continuous fluorscopic beam Screening for pre-existing conditions Patients with genetic predisposition (ataxia-telangiectasia) Diabetes mellitus Connective tissue disease (SLE, SCL, MCTD)
  • FDA threshod absorbed dose in skin of 2 rad/min (0.02 Gy,min) and 20 rad/min (0.2 Gy/min) of areas of skin irradiated by a stationary continuous fluorscopic beam Screening for pre-existing conditions Patients with genetic predisposition (ataxia-telangiectasia) Diabetes mellitus Connective tissue disease (SLE, SCL, MCTD)
  • 3x 3 cm distal left leg ulcer with non undermined border DP pulses on left foot were not palpable Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli),
  • Focal granulation tissue with white to yellowish film in other area r/o vasculitis, carcinoma, infection, stasis ulcer, pyoderma gangrenosum Patient had a skin biopsy performed for histology and culture (fungal, bacterial, and acid fast bacilli),
  • Importance of punch biopsy
  • Diff Dx: Reactive Angioendotheliomatosis Acroangiodermatitis Kaposi’s Sarcoma Angiosarcoma Other vascular tumors Glomeruloid hemangioma Tufted angioma
  • Our case demonstrated a more lobular proliferation than that seen in previous cases
  • At the time of presentation, brown-black hyperkeratotic , hyperlinear, ridged, verrucous plaques were present over the extensor surfaces of the knees, elbows, and ankles. Similar plaques affected the flexural areas of the axilla, antecubital fossa, and popliteal fossa. (Fig )Yellow-brown, confluent, lichenified, and fissured hyperkeratotic plaques involved most of the palms and soles, with extension onto the dorsal aspects of the hands and feet. (Fig ) Polycyclic, psoriasiform, erythematous patches of variable size with annular scale involved sixty percent of the trunk and extremities. (Fig )Examination of the teeth, hair, and nails revealed no abnormal findings. A KOH from the leading edge of a scaly patch showed no fungal elements. A biopsy was taken from an annular, scaly patch on the left forearm.
  • Routine laboratory evaluation including a blood count, chemistry panel, and hepatic panel were within normal limits.
  • This is consistent with the fact that keratin 10 is not significantly expressed in acral skin and mutations in keratin 10 do not cause palmoplantar keratoderma

Clinicopathologic Case Studies Presentation Transcript

  • 1. Interesting and Unusual Clinicopathologic Case Studies Narayan S. Naik, MD Finan Templeton Dermatopathology Associates
  • 2. Overview
    • Case History
    • Clinical Photos
    • Pathology
    • Additional Studies
    • Diagnosis and Discussion
    • Treatment
  • 3. Overview
    • Importance of adequate biopsy
    • Importance of clinicopathologic correlation
    • Importance of correlation with laboratory and culture studies
  • 4. CASE 1
  • 5. CASE 1
    • 71 y/o Cauc M with a six month hx of “sores” on left dorsal hand and left wrist
    • No improvement with two courses of antibiotics
    • PMHx: hx renal transplant for chronic ESRD
    • SocHx: +fisherman, no hx gardening or pets
  • 6.  
  • 7.  
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  • 11.  
  • 12.  
  • 13.  
  • 14.  
  • 15.  
  • 16.  
  • 17.  
  • 18.  
  • 19.  
  • 20. PAS
  • 21.  
  • 22. CASE 1 Tissue Culture Results
    • Cultures for bacterial and mycobacterial organisms showed no growth
    • Fungal culture grew yeast-like colonies of Prototheca wickerhamii
  • 23. CASE 1 Diagnosis? Cutaneous Protothecosis
  • 24. Cutaneous Protothecosis
    • Caused by achlorphyllic algae Prototheca
      • Rare cause of infection in humans
      • Majority caused by P. wickerhamii species
    • Infections mainly seen in immunocompromised individuals
      • Localized cutaneous or subcutaneous infection
      • Disseminated disease
      • Olecranon bursitis secondary to Prototheca may be seen in immunocompetent individuals
    • Usually a history of trauma with exposure to contaminated water
  • 25. Cutaneous Protothecosis
    • Histopathology:
      • Spherical to ovoid organisms with thick cell wall
      • Divide by internal septation (endosporulation) with characteristic morula forms
      • May be difficult to see on H&E but stain well with fungal stains (PAS, GMS)
    • Culture:
      • White yeast-like colonies on SDA at 30 0 C
      • Organisms with sporangia can be identified on lactophenol cotton blue stained wet preps
      • Commercially available biochemical assimilation tests to identify specific species
  • 26. Cutaneous Protothecosis
    • Treatment:
      • May be difficult
      • No standard regimen
      • Surgical excision for localized lesions
      • Amphotericin B or ketoconazole +/- tetracycline
  • 27.  
  • 28. CASE 2
  • 29. CASE 2
    • 78 y/o Cauc M inpatient with a three day hx of worsening “cellulitis” on right forearm associated with fever
    • Site of previous intravenous catheter
    • PMHx: AML s/p chemo with neutropenia on broad spectrum antibiotics
    • Several aerobic and anaerobic blood cultures had been negative
  • 30.  
  • 31.  
  • 32.  
  • 33.  
  • 34.  
  • 35.  
  • 36.  
  • 37. PAS
  • 38. PAS
  • 39. PAS
  • 40. GMS
  • 41.  
  • 42. CASE 2 Tissue Culture Results
    • Cultures for bacterial and mycobacterial organisms showed no growth
    • Fungal culture grew Rhizopus sp .
  • 43. CASE 2 Diagnosis? Cutaneous Zygomycosis
  • 44. Cutaneous Zygomycosis
    • Opportunistic infection caused by Rhizopus, Mucor, or Absidia species
    • Risk factors: diabetes (esp DKA), other metabolic acidosis, burns, organ transplants, hematologic malignancies with neutropenia
    • Clinical infections may be subdivided (rhinocerebral, pulmonary, hematogenous, gastrointestinal, and cutaneous)
  • 45. Cutaneous Zygomycosis
    • Cutaneous infections
      • Primary – rare, may be seen in contaminated dressings, burns, IV catheter sites
      • Secondary – hematogenous seeding from lesion elsewhere in body
    • Typical presentations:
      • Indurated tender plaque with dusky purpuric center
      • Necrotizing cellulitis
      • Echthyma gangrenosum like lesions
  • 46. Cutaneous Zygomycosis
    • Histopathology:
      • Suppuration and necrosis, occasionally only minimal inflammation
      • Broad non-septate hyphae with right angle branching
      • Angioinvasive with thrombosis and infarction
      • Tissue invasion important to demonstrate pathogenicity as Zygomycetes may be frequently cultured from skin surface swabs
    • Treatment:
      • Surgical debridement
      • Treatment of underlying predisposing condition
      • Amphotericin B (liposomal more effective)
  • 47. ASPERGILLOSIS ZYGOMYCOSIS
  • 48.  
  • 49. CASE 3
  • 50. CASE 3
    • 46 y/o AA M inpatient with one month hx of non-healing right leg ulcers
    • ? Hx of prior trauma to area
    • Unresponsive to broad spectrum antibiotics or local wound care
    • PMH: s/p lung transplant on chronic immunosuppressives
  • 51.  
  • 52.  
  • 53.  
  • 54.  
  • 55.  
  • 56.  
  • 57.  
  • 58.  
  • 59.  
  • 60.  
  • 61.  
  • 62. GMS
  • 63. GMS
  • 64. PAS
  • 65. PAS
  • 66.  
  • 67. CASE 3 Tissue Culture Results
    • Tissue cultures for bacterial and mycobacterial organisms showed no growth
    • Fungal culture:
  • 68.  
  • 69.  
  • 70.  
  • 71.  
  • 72.  
  • 73. CASE 3 Diagnosis? Cutaneous Alternariosis (with Candidiasis)
  • 74. Cutaneous Alternariosis
    • Alternaria are classified as a phaeohyphomycosis – a subset of dematiaceous (pigmented) fungi found in air, soil, and plants
    • Alternaria organisms commonly colonize human skin but are rarely pathogenic in humans
    • Alternaria alternata is most frequent pathogenic species
    • Mixed infection with Candida albicans has been reported 1,2
    1 Bang Peterson et al. Arch Dermatol . 1976; 94: 201-207 2 Higashi et al. Arch Dermatol 1973; 108: 558-560
  • 75. Cutaneous Alternariosis
    • Majority of cases of cutaneous alternariosis have been in immunocompromised patients
      • Mainly solid organ transplant recipients
      • Relatively rare in HIV/AIDS patients
    • Routes of infection:
      • Traumatic inoculation
      • Colonization of pre-existing lesions such as eczema
      • Rarely by hematologic spread, usually from pulmonary infection
  • 76. Cutaneous Alternariosis
    • Cutaneous lesions:
      • Heterogeneous and nonspecific
      • Develop most commonly on exposed sites such as lower extremity, forearms, hands, face
      • Often have chronic fluctuating course
  • 77. Cutaneous Alternariosis Histopathology
    • Dermal suppurative and granulomatous inflammation with abscess formation
    • Rarely noncaseating sarcoidal-like or plasma-cell rich granulomas may be present
    • Overlying ulceration and pseudoepitheliomatous hyperplasia with microabscesses
  • 78. Cutaneous Alternariosis Histopathology
    • May be present both as both hyphal and spore forms in tissue:
      • Broad, septate hyphal forms
      • Round to oval thick walled spores
      • Pigmented hyphal elements may also stain with Fontana-Masson
  • 79.  
  • 80. Cutaneous Alternariosis Culture
    • Correlation with clinical presentation and histology is important to distinguish between contamination, colonization, and pathogenicity
    • Forms brown-black colonies on SDA agar
    • Conidia divide in two directions - often resemble “hand grenades” microscopically
  • 81.  
  • 82. Cutaneous Alternariosis Treatment
    • Surgical excision in localized lesions
    • Reduction of immunosuppression
    • Antifungal agents (IV, oral and intralesional) variably successful
      • Amphotericin B
      • Itraconazole
      • Dosing and duration regimens not established
    • Relapses often occur even after prolonged treatments
  • 83.  
  • 84. CASE 4
  • 85. CASE 4
    • 30 y/o Asian M presented to emergency department with fever, cough, and widespread skin eruption worsening over last two weeks
    • PMHx: none
    • SocHx: recent immigrant from Thailand
  • 86.  
  • 87.  
  • 88.  
  • 89.  
  • 90.  
  • 91.  
  • 92.  
  • 93.  
  • 94.  
  • 95.  
  • 96. PAS
  • 97. GMS
  • 98. GMS
  • 99.  
  • 100. CASE 4 Additional studies and cultures
    • Patient diagnosed as HIV+ , CD4 count: 55
    • Skin tissue cultures for bacterial and mycobacterial organisms were negative
    • Fungal culture:
  • 101. 37 ˚ C yeast 25 ˚ C mold
  • 102. 25 ˚ C 37 ˚ C Mold Yeast
  • 103. 37 0 C YEAST
  • 104. 25 0 C MOLD
  • 105.  
  • 106. CASE 4 Diagnosis? Cutaneous Penicilliosis
  • 107. Penicilliosis
    • Disseminated fungal infection secondary to Penicillium marneffei, the only pathogenic and thermally dimorphic Penicillium species
    • Predilection for reticuloendothelial system with resultant fungemia and infection of mononuclear phagocytes
  • 108. Penicilliosis
    • Endemic in SE Asia
      • Third most common opportunistic infection in the region
      • > 80% patients have underlying HIV/AIDS
    • Mode of transmission unclear
      • Associated with recent exposure to soil especially during rainy season
      • Likely mode is ingestion or inhalation of fungal conidiophores
      • Animal reservoir: bamboo rat ( Rhizomys species) but no reports of direct transmission
  • 109. Penicilliosis
    • Systemic signs and symptoms
      • Fever, weight loss, anemia
      • Pulmonary symptoms / cough
      • Lymphadenopathy, hepatosplenomegaly
    • Cutaneous lesions:
      • Predilection for upper body
      • Discrete flesh-colored “molluscoid” papules
      • Infrequent papular or ulcerative lesions on mucosal surfaces
  • 110. “ Molluscoid” lesions in AIDS
    • Molluscum contagiosum
    • Cryptococcus neoformans
    • Coccidiodes immitis
    • Histoplasma capsulatum
    • Penicillium marneffei
    • Pneumocystis carinii
    • Pityrosporum folliculitis
  • 111. Penicilliosis Histopathology
    • Most common pattern in immunocompromised patients:
      • Zones of focal necrosis and suppuration
      • Surrounding diffuse infiltration of histiocytes engorged by proliferating yeast
    • Differential diagnosis of “parasitized histiocytes”
  • 112. Differential Diagnosis of “Parasitized Histiocytes”
    • R hinoscleroma
    • Hist oplasmosis
    • Gra nuloma inguinale
    • P enicilliosis
    • L eishmaniasis
    • L epromatous L eprosy
    • “ R avenous Hist iocytes Gra b P acked L unches”
  • 113. Penicillium marneffei Histoplasma capsulatum
  • 114. Penicillium marneffei Histoplasma capsulatum
  • 115. Differentiation between Histoplasmosis and Penicilliosis
    • Clinical features
    • Histopathologic features
    • Culture characteristics
  • 116. Histoplasmosis vs. Penicilliosis Clinical Features
    • Histoplasmosis
      • Skin involvement INFREQUENT
      • Involves lung and reticuloendothelial system
      • Predisposition for adrenals and mucosal surfaces
    • Penicilliosis
      • Skin involvement COMMON
      • Involves lung and reticuloendothelial system
      • Spares adrenals and infrequently affects mucosal surfaces
  • 117. Histoplasmosis vs. Penicilliosis Histopathologic Features
    • Histoplasmosis
      • 2-5 microns
      • Uniform round to oval yeast
      • Reproduction by budding (narrow neck spore)
    • Penicilliosis
      • 1-8 microns
      • Pleomorphic round to sausage shaped yeast
      • Reproduction by fission (prominent central wall)
  • 118. Penicilliosis - Septation Histoplasmosis - Budding
  • 119. Culture Characteristics Histoplasma Penicillium 25 ˚ C mold 25 ˚ C mold
  • 120. Culture Characteristics Histoplasma Penicillium
  • 121. Penicilliosis Treatment
    • High response rate with systemic antifungals
      • Amphotericin B followed by oral itraconzaole
      • Long term prophylaxis with itraconazole to reduce high relapse rate
    • HAART for underlying HIV infection
      • May obviate need for long-term antifungal prophylaxis.
  • 122.  
  • 123. CASE 5
  • 124. CASE 5
    • 69 y/o AA F presents with one year hx of pruritic lesions on arms and upper back, previously diagnosed and treated as prurigo nodules
    • Skin lesions have persisted despite treatment with high potency topical and intralesional corticosteroids
    • ROS: Patient was seeing a hematologist for evaluation of episodes of bleeding and anemia
  • 125.  
  • 126.  
  • 127.  
  • 128.  
  • 129.  
  • 130.  
  • 131.  
  • 132.  
  • 133.  
  • 134.  
  • 135.  
  • 136. PAS
  • 137. KAPPA
  • 138. DIF - IgM
  • 139.  
  • 140. CASE 5 Additional Laboratory Studies
    • Hb / Hct: 8.8 / 26.4
    • Serum IgM level: 13.3 g/L (NL 0.45-2.25)
    • Serum protein electrophoresis: IgM Kappa monoclonal peak
    • Bone marrow bx: diffusely infiltrated by lymphoplasmacytoid cells
  • 141. CASE 5 Diagnosis? Cutaneous Macroglobulinosis (IgM Storage Papule)
  • 142. Cutaneous Macroglobulinosis
    • Waldenstrom’s macroglobulinemia – lymphoproliferative d/o with IgM producing lymphoplasmacytoid cells
    • Cutaneous manifestations usually non-specific -urticaria, purpura, ulcers
    • Two types of specific skin lesions (both relatively rare)
      • Infiltrative violaceous plaques
      • IgM storage papule
    • Usually develop late in course of disease, but may be presenting feature
  • 143. Cutaneous Macroglobulinosis
    • Infiltrative violaceous plaque
      • More common
      • Usually on extremities, ears, or face
      • Dermal infiltrate of monomorphous lymphoplasmacytoid cells
    • IgM storage papule
      • Rare
      • Extensor surfaces of elbows, knees, buttocks usual locations
      • Dermal deposits of monoclonal IgM
      • May fluctuate with course of disease
  • 144. Cutaneous Macroglobulinosis Histopathology
    • Nodular dermal collections of eosinophilic, homogenous material resembling amyloid
    • Material is strongly PAS (+) but amyloid stains (-)
    • May have associated cellular infiltrate of lymphocytes and lymphoplasmacytoid cells
    • Diff Dx: Amyloidosis,colloid milium, erythropoietic protoporphyria, lipoid proteinosis
  • 145. Cutaneous Macroglobulinosis Additional Studies
    • Immunohistochemistry
      • Can demonstrate monoclonal light chain restriction with kappa and lambda stains
    • Immunofluorescence
      • Deposits of monoclonal IgM strongly positive
    • Electron microscopic studies
      • Amorphous electron dense granular material
      • Non-branching fibrillar material with cross striations
      • Distinct from amyloid
  • 146. Cutaneous Macroglobulinosis Treatment
    • Cutaneous lesions usually respond to treatment of underlying disease and declining serum IgM levels
      • Plasmapheresis
      • Chemotherapy
        • Chlorambucil
        • Glucocorticoids, cladribine, cyclophosphamide
        • Rituximab
      • XRT for localized disease
      • Transplantation
    • Long term follow-up not available
  • 147.  
  • 148. CASE 6
  • 149. CASE 6
    • 53 y/o Hisp F presents with four year hx of progressively darkening patches over cheeks
    • Patient had used many creams on face without resolution of eruption, unsure of their names
    • PMHx: HTN controlled with amlodipine and atenolol
  • 150.  
  • 151.  
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  • 154.  
  • 155.  
  • 156.  
  • 157. CASE 6 Diagnosis? Exogenous Ochronosis
  • 158. Exogenous Ochronosis
    • Acquired disorder characterized by deposition of yellow-brown/ocher pigment ( homogentisic acid ) on collagen fibers
    • Majority of cases felt to be secondary to extended use of hydroquinone -containing compounds
    • Other implicated compounds include phenol, picric acid, mercury, resorcinol, and oral and intramuscular administration of antimalarial drugs
  • 159. Exogenous Ochronosis
    • Mechanism: local inhibition of homogentisic acid oxidase with subsequent accumulation and polymerization of homogentisic acid on dermal collagen fibers
    • No systemic features such as arthropathy or darkening of urine or sweat as in hereditary alkaptonuria (endogenous ochronosis)
  • 160. Exogenous Ochronosis
    • Clinical presentation:
      • Blue-black macules at sites of application
      • Malar areas most common but temples, neck, ears may also be affected
      • Fine “caviar-like” papules or pigmented colloid milia may develop in some patients
    • Epidemiology:
      • Vast majority of cases in South African black population
      • Relatively uncommon among blacks in America
      • Occasionally rare reports in Caucasians and Hispanics
  • 161. Exogenous Ochronosis Histopathology
    • Similar findings in endogenous and exogenous forms
    • Earliest lesions – basophilia of collagen in upper dermis
    • Well-developed lesions – Sharply defined irregular, crescentic, or banana-shaped homogenous ocher-colored deposits
    • Occasional findings include transepidermal elimination of deposits and associated granulomatous inflammation
  • 162. Exogenous Ochronosis Treatment
    • Successful treatment is usually difficult
    • Most topical preparations, liquid nitrogen, and chemical peels often ineffective
    • Dermabrasion, CO 2 laser, and Q-switched ruby and alexandrite lasers have shown success in small numbers of patients
  • 163.  
  • 164. CASE 7
  • 165. CASE 7
    • 70 y/o Cauc F presents with six month hx of non-pruritic eruption in groin and extremities
    • Eruption has been treated as nummular eczema with superimposed impetigo and candidiasis
    • Patient has received multiple courses of oral and IM steroids as well as oral antibiotics and antifungals
    • ROS: One year hx of weight loss with episodes of diarrhea
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  • 183.  
  • 184. CASE 7 Additional Laboratory Studies
    • Glucose: 156
    • AST /ALT: 348 / 171
    • Alkaline Phosphatase: 415
    • Amylase / Lipase: WNL
    • Hb / Hct: 9.9 / 29.7
    • Albumin: 2.8 (NL 3.5-5.8)
    • Zinc: 75 mg/dl (NL 65-256)
    • Glucagon: 3800 pg/ml (NL 50-200)
  • 185. CASE 7 Additional Laboratory Studies
    • CT scan abdomen – revealed mass in pancreatic neck
    • Patient underwent a resection of the mass:
    • Pathology:
  • 186.  
  • 187.  
  • 188.  
  • 189. GLUCAGON
  • 190.  
  • 191. CASE 7 Diagnosis? Necrolytic Migratory Erythema (Glucagonoma Syndrome)
  • 192. Necrolytic Migratory Erythema
    • Distinctive skin eruption usually associated with glucagon secreting alpha islet cell tumor of pancreas
    • Associated features:
      • Glossitis/stomatitis/angular cheilitis
      • Anemia, weight loss, fatigue, diarrhea
      • Hyperglycemia/ diabetes, hypoaminoacidemia
    • Liver disease/ cirrhosis often present in cases without a glucagonoma
    • >50% cases have metastatic disease at time of diagnosis
  • 193. Necrolytic Migratory Erythema
    • Clinical lesions:
      • Recurrent waves of annular and circinate erythema with superficial necrosis
      • Exfoliation of skin with vesicles and flaccid bullae which rupture to form erosions and crusted plaques
      • Hyperpigmentation and scaling with healing
      • Lesions often in various stages of development
    • Clinical distribution:
      • Groin and perioral skin almost always involved
      • Lower abdomen, thighs, distal extremities also frequent sites
  • 194. Necrolytic Migratory Erythema Histopathology
    • Several patterns depending on stage of lesion
      • Psoriasiform epidermal hyperplasia with pallor and presence of vacuolated keratinocytes in upper epidermis
      • May have areas of focal and confluent necrosis
      • Subcorneal pustulation and neutrophilic spongiosis may be present
      • Confluent parakeratosis with scale-crust
      • Vascular dilatation and intraepidermal and superficial dermal edema
  • 195. Necrolytic Migratory Erythema Treatment
    • Resection of underlying tumor
    • Chemotherapy for metastatic dz
      • Streptozotocin
      • Octreotide
    • Supplementation of amino acids, zinc, and essential fatty acids can also result in resolution of eruption
  • 196.  
  • 197. CASE 8
  • 198. CASE 8
    • 53 y/o AA M presents with ten year hx of generalized pruritic eruption
    • Eruption began on neck and chest and spread to involve face, lower trunk, extremities
    • ROS: difficulty swallowing, hoarseness, extremity muscle weakness
    • PMHx: HTN, carpal tunnel syndrome
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  • 215. COLL. IRON
  • 216. COLL. IRON
  • 217. COLL. IRON
  • 218. COLL. IRON
  • 219. CASE 8 Additional Laboratory Studies
    • CBC, LFT’s, TFT’s, electrolytes WNL
    • Total serum protein: 8.8 (NL 6.1-8.5)
    • Albumin: 4.3 (NL 2.6-5.2)
    • Serum IgG level: 18.0 g/L (NL 7.0-13.0)
    • Serum protein electrophoresis: diffuse band in slow gamma region, reacting on immunofixation as IgG lambda
  • 220. CASE 8 Diagnosis? Scleromyxedema
  • 221. Scleromyxedema
    • Rare chronic and progressive cutaneous mucinosis in which generalized lichenoid papules and plaques are present with skin thickening
    • Paraproteinemia, usually of IgG lambda type almost always present
    • Generally middle-aged to elderly adults
    • Patients may have associated hepatitis C
  • 222. Scleromyxedema
    • Cutaneous disease features:
      • Multiple waxy papules coalescing into plaques
      • May have linear array
      • Skin often diffusely indurated limiting ROM
    • Distribution:
      • Dorsal hands, face, elbows, extensor extremities most commonly affected
      • “ Leonine facies” may develop
      • “ Doughnut sign” around PIP joint
  • 223. Scleromyxedema
    • Visceral disease features:
      • Gastrointestinal involvement most frequent
        • Dysphagia from esophageal involvement
      • Pulmonary disease
        • SOB from obstructive or restrictive lung disease
      • Musculoskeletal
        • Proximal muscle weakness / inflammatory myopathy
        • Arthralgia / inflammatory arthritis
      • Neurologic
        • Peripheral neuropathies
        • CNS disturbances (confusion, dizziness, dysarthria, seizures, paralysis, syncope, coma
        • Carpal tunnel syndrome
  • 224. Scleromyxedema Histopathology
    • Dermal deposits of mucin in association with proliferation of fibroblasts and collagen in upper and mid-dermis
    • Areas of fibroblasts and collagen may have irregular or whorled arrangement
    • Inflammation usually sparse
  • 225. Scleromyxedema Treatment
    • Difficult, prognosis poor
    • Physical therapy
    • High dose corticosteroids
    • Plasma exchange +/- melphalan , cyclophosphamide
    • Retinoids, IVIG, Electron beam, PUVA, IFN, cyclosporin, thalidomide have helped selected patients
  • 226.  
  • 227. CASE 9
  • 228. CASE 9
    • 51 y/o Cauc F presents with one and a half year hx of eruption on legs and lower abdomen
    • Lesions were increasing in size and number over this period
    • ROS: Patient was being evaluated by hematologist for leukopenia and splenomegaly
    • PMHx: Long history of arthritis in hands, no history of diabetes or increased lipids
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  • 244.  
  • 245. CASE 9 Additional Laboratory Studies
    • WBC 2.3, Hb/ Hct: 14/42, Plt: 119
    • Blood glucose: 83
    • Lipid profile: WNL
    • Skeletal surveys and bone scan WNL
    • Serum IgG level: 20.8 g/L (NL 7.0-13.0)
    • Serum protein electrophoresis: spike in mid- gamma region, reacting on immunofixation as IgG kappa
    • Bone marrow bx: mildly elevated % plasma cells
  • 246. CASE 9 Diagnosis? Necrobiotic Xanthogranuloma
  • 247. Necrobiotic Xanthogranuloma
    • Rare chronic and progressive disorder characterized by multiple painless violaceous xanthomatous nodules and indurated plaques
    • Atrophy, ulceration, and telangiectasia may be present
    • Predominantly involves periorbital area but trunk and limbs often involved
    • IgG paraproteinemia, usually kappa, is usually present as an isolated finding in approximately 80% patients
    • Usually in middle aged to elderly men and women
  • 248. Necrobiotic Xanthogranuloma
    • Ophthalmologic involvement usually most common and account for most severe complications:
      • Episcleritis, keratitis, ulceration of palpebral fissure, blindness
    • Associated systemic findings:
      • Frequent: leukopenia, splenomegaly
      • Infrequent: hypocomplementemia, hyperlipidemia, cryoglobulinemia
  • 249. Necrobiotic Xanthogranuloma Histopathology
    • Extensive necrobiosis of collagen with surrounding granulomatous inflammation involving the dermis and subcutaneous tissue
    • Granulomatous inflammation usually includes histiocytes, foam cells, and multinucleate giant cells (both Touton type and bizarre foreign body type)
    • Cholesterol clefts, lymphoid nodules, and plasma cell collections may be present
    • Usually more cellular and has more atypical giant cells than necrobiosis lipoidica
  • 250. Necrobiotic Xanthogranuloma Treatment
    • Cytotoxic agents
      • Chlorambucil
      • Melphalan
      • Nitrogen mustard
      • Cyclophosphamide
      • Methotrexate
    • Systemic corticosteroids
    • Plasmapheresis
    • Localized XRT
  • 251.  
  • 252. CASE 10
  • 253. CASE 10
    • 60 y/o male presented with 2 month hx ulcerations bilateral dorsal hands occurring after minor trauma
    • Lesions initially began as small papules that expand to plaques and ulcerate
    • No response to two courses of antibiotics
    • ROS: denies fever, no hx of malignancy or gastrointestinal disorder
    • PMH: HTN
  • 254.  
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  • 264. CASE 10 Additional Laboratory Studies
    • CBC WNL
    • Radiologic studies: no underlying osteomyelitis
    • Two sets of tissue cultures: No growth of bacteria, fungi, or mycobacteria
  • 265. CASE 10 Diagnosis? Neutrophilic Dermatosis of the Dorsal Hands
  • 266. Neutrophilic Dermatosis of the Dorsal Hands (NDDH)
    • First described in 1995 as “pustular vasculitis of the hands” 1
    • Term “neutrophilic dermatosis of the dorsal hands” proposed in 2000 for cases with a similar presentation but no histologic evidence of vasculitis
    • Violaceous papulonodules evolving into spreading ulcerating plaques usually on radial aspect of dorsal hands
    • Total of 52 cases have been reported in literature
    1 Strutton et al. J Am Acad Dermatol . 1995; 32: 192-198 2 Galaria et al. J Am Acad Dermatol . 2000;43: 870-874
  • 267. NDDH
    • Most likely represents a localized variant of Sweet’s syndrome
    • Vesiculobullous (atypical) pyoderma gangrenosum may also be the same disease
  • 268. NDDH vs. Sweet’s Syndrome
    • F:M ratio: 2.2
    • Mean age onset: 60
    • % w/malignancy: 27%
    • % w/ IBD: 15%
    • % w/ vasculitis: 25%
    • % steroid response: 71%
    • F:M ratio: 3.7
    • Mean age onset: 53
    • % w/malignancy: 21%
    • % w/ IBD: 16%
    • % w/ vasculitis: 18%
    • % steroid response: 97%
    Walling et al. Arch Dermatol . 2006; 142: 57-63
  • 269. NDDH and atypical pyoderma gangrenosum (PG)
    • Atypical PG usually presents as hemorrhagic bullous lesions which superficially ulcerate
    • Usual presentation is on upper extremities, especially dorsal hands
    • More often associated with malignancy and underlying systemic disease
    • Prompter remission
    • Clinically and histopathologically very similar presentation to NDDH
  • 270. NDDH Histopathology
    • Diffuse neutrophilic infiltrate
    • Papillary dermal edema
    • +/- small vessel leukocytoclastic vasculitis
    • +/- overlying ulceration and pseudoepitheliomatous hyperplasia
  • 271. NDDH and vasculitis
    • Evidence of leukocytoclastic vasculitis present in 27% patients with NDDH 1
    • Comparable percentage in 2 series of patients with classical Sweet’s syndrome (18-30%) 2,3
    • Vasculitis probably represents a secondary process as a result of the brisk neutrophilic infiltrate and accompanying cytokine and enzymatic cascade
    1 Walling et al. Arch Dermatol . 2006; 142: 57-63 2 Malone et al. Arch Dermatol. 2002: 138: 345-349 3 Jordaan HF. Am J Dermatopathol. 1989; 11: 99-111
  • 272. NDDH Treatment
    • Systemic corticosteroids
    • Steroid sparing immunosuppressants
    • Dapsone
    • Minocycline
    • Recurrences are common
  • 273.  
  • 274. CASE 11
  • 275. CASE 11
    • 77 y/o AA male presents with 1 year hx of a lesion on upper back
    • Area had initially began as localized oval area of painful erythema which then became ulcerated and indurated
    • ROS: Did not recall any trauma to area, denied any new medications
    • PMH: Prostate AdenoCA, HTN, CAD, and hyperlipidemia
  • 276.  
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  • 292. CASE 11 Additional Clinical History
    • Upon further directed questioning, patient remembered he had undergone four hour coronary stenting procedure prior to onset of lesion
    • He had a repeat procedure one day later
  • 293. CASE 11 Diagnosis? Fluoroscopy-induced Radiation dermatitis
  • 294. Fluoroscopy-induced Radiation Dermatitis
    • Increased incidence with use of fluoroscopic guided interventional procedures, especially coronary artery stenting and angioplasty
    • Majority of patients have been middle-aged to elderly men
    • Typical clinical presentation:
      • Pruritic to painful oval to square shaped lesions on scapular region of the back corresponding to location of beam
      • Often began as erythematous or vesicular patches progressing to indurated poikilodermatous plaques with secondary necrotic ulceration
  • 295. Stone MS et al. J Am Acad Dermatol. 1998; 38: 333-6 EARLY LATE
  • 296. Radiation Dermatitis Histopathology
    • Findings depend on stage of lesion biopsied
    • Previously classified into acute and chronic stages
    • A subacute stage with clinical features intermediate between acute and chronic stages and distinctive histologic features has been recognized 1
    1 Leboit PE. J Am Acad Dermatol . 1989: 20: 236-41
  • 297. Radiation Dermatitis Histopathology
    • Acute Stage (Uncommonly biopsied)
      • 2 to 7 days after exposure
      • Intracellular edema, pyknotic nuclei, fibrin thrombi in small vessels with hemorrhage and dermal edema
    • Chronic Stage (Most commonly biopsied)
      • Months to years after exposure
      • Epidermal atrophy and /or acanthosis
      • Dermal sclerosis with telangiectases and loss of adnexal structures and presence of atypical “radiation fibroblasts”
  • 298. Radiation Dermatitis Histopathology
    • Subacute Stage
      • Weeks to months after exposure
      • Lichenoid interface dermatitis with features mimicking acute graft versus host disease or a fixed drug eruption
      • Immunohistochemical studies suggest a cytotoxic T-cell and natural killer cell process
  • 299. Fluoroscopy-induced Radiation Dermatitis - Treatment
    • Can be difficult as areas usually show poor or very delayed wound healing
    • Superficial injures – local wound care
    • More necrotic lesions may require surgical excision with split or full thickness skin grafts
  • 300. Fluoroscopy-induced Radiation Dermatitis - Prevention
    • Screening for pre-existing conditions
    • Establishment of FDA protocols
      • Continuous monitoring of cumulative radiation doses during interventional fluoroscopic procedures
      • Recording absorbed doses that approach or exceed threshold for skin injury
    • Limiting exposure of specific site:
      • Reducing size of exposed area
      • Using different projections
  • 301.  
  • 302. CASE 12
  • 303. CASE 12
    • 69 y/o female presents with three week hx of an intermittently painful left leg ulcer, developing after minor trauma.
    • Progressively more painful with conservative management (leg elevation, local wound care)
    • Ulcer had not respond to 2 week course of cephalexin
    • ROS: prior hx of ulcer on other leg which healed spontaneously
    • PMH: HTN, hx of colon rupture and colostomy
  • 304.  
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  • 315. CD31
  • 316. CD31
  • 317. CD31
  • 318.  
  • 319. CASE 12 Additional Laboratory Studies
    • Tissue cultures: showed no growth
    • Non-invasive vascular studies showed severe bilateral ischemic disease in legs (L>R)
  • 320. CASE 12 Diagnosis? Diffuse Dermal Angiomatosis
  • 321. Diffuse Dermal Angiomatosis
    • First reported in 1994 as a variant of reactive angioendotheliomatosis (RAE). 1
    • Painful violaceous plaques with ulceration usually on lower extremities
    • Majority of patients have evidence of severe peripheral atherosclerotic disease
    • Lesions often develop rapidly but disappear quickly after surgical revascularization
    1 Krell JM, Sanche RL, Solomon AR. J Cutan Pathol . 1994; 21: 363
  • 322. Draper BK, Boyd AS. J Cutan Pathol . 2006: 33: 646-648
  • 323. Diffuse Dermal Angiomatosis Pathogenesis
    • Not fully elucidated
    • Possible explanations:
      • Tissue ischemia induces local increase in vascular endothelial growth factor (VEGF) which induces endothelial cell proliferation
      • Irregular intimal surface of partially occluded large vessels may provide a source of emboli that are carried distally to small dermal vessels where they can induce endothelial cell hyperplasia (similar to Masson’s tumor)
  • 324. Diffuse Dermal Angiomatosis Histopathology
    • Diffuse dermal interstitial proliferation of endothelial cells (CD31+)
    • Proliferating cells may show a spindled appearance with vacuolated cytoplasm and formation of vascular lumina
    • Absence of atypical endothelial cells or mitoses
    • Hemosiderin deposition and extravasated erythrocytes may be present
  • 325. Draper BK, Boyd AS. J Cutan Pathol . 2006: 33: 646-648
  • 326. Diffuse Dermal Angiomatosis Treatment
    • Surgical revascularization has resulted in resolution of lesions in most cases
    • Isotretinoin successfully used in 1 case described from breast 1
    1 McLaughlin ER et al. J Am Acad Dermatol . 2001; 45: 462
  • 327.  
  • 328. CASE 13
  • 329. CASE 13
    • 21 y/o Asian F presents with long hx episodic and recurrent erythematous scaly patches involving trunk and extremities
    • Eruption has been present since birth and has been noted to migrate over her body before fading over weeks to months
    • Since age five, patient has had a fixed palmoplantar keratoderma
    • By adolescence, persistent linear, corrugated verrucous plaques had developed over flexural and extensor surfaces of several joints
  • 330. CASE 13
    • ROS: No hx blisters, No abnormalities with hair, nails, teeth, or mucous membranes
    • FMHx: Mother and multiple maternal relatives with PPK and verrucous plaques; one male cousin with similar migratory patches
    • PMHx: None
    • Meds: Oral contraceptives
  • 331.  
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  • 344.  
  • 345. CASE 13 Additional Laboratory Studies
    • CBC WNL
    • Chemistry panel WNL
    • Hepatic panel WNL
    • Genetic studies:
      • detected a keratin 1 mutation in the patient and her mother but not in the father or an unaffected sister
  • 346. CASE 13 Diagnosis? Annular Epidermolytic Ichthyosis
  • 347. Annular Epidermolytic Ichthyosis
    • Annular epidermolytic ichthyosis (AEI)
      • Rare phenotypic variant of bullous congenital ichthyosiform erythroderma (BCIE) first reported in 1992 1
        • +/- widespread erythroderma and blisters at birth
        • Episodic migratory annular and polycyclic erythematous plaques on trunk and proximal extremities
        • Fixed corrugated ridged hyperkeratotic plaques develop over the body folds and joints similar to classic BCIE
        • Variable presence of fixed palmoplantar keratoderma
        • Hair, nails, and mucous membranes unaffected
      • Clinical presentation varies markedly between family members and over the lifetime of each individual
    1 Sahn et al. J Am Acad Dermatol. 1992;27:348-35
  • 348. Annular Epidermolytic Ichthyosis
    • Seven previous kindreds reported in the literature
    • Mutations often found in 2b segment of of Keratin 1 and 10 genes (similar to BCIE)
      • Keratin 10 mutations – no associated PPK
      • Keratin 1 mutations - associated PPK
  • 349. Annular Epidermolytic Ichthyosis Histopathology
    • Epidermolytic hyperkeratosis (EHK)
      • Hyperkeratosis of the stratum corneum
      • Vacuolization with irregular keratohyalin granules within the spinous and granular layers
    • Similar histology seen in both migratory patches or in fixed verrucous plaques
    • Pattern identical to that seen in classic EHK-BCIE, hereditary epidermolytic PPK and sporadic epidermolytic acanthomas.
    • Epidermal nevi with EHK on histology thought to represent a mosaic form of the disorder in carriers
  • 350. Annular Epidermolytic Ichthyosis Treatment
    • Annular plaques
      • Topical and oral retinoids
      • Present patient showed good response to topical tazarotene
      • Natural or artificial UV light treatments
    • Palmoplantar keratoderma
      • Propylene glycol
      • Urea
  • 351.  
  • 352. CASE 14
  • 353. CASE 14
    • 45 y/o Cauc F presents with hx pruritic lesions involving right side of body since age 18 involving trunk and extremities
    • Has had little response to topical steroids, topical and oral retinoids
    • ROS: Denies any nail or oral abnormalities, no neurologic disorders
    • PMHx: none
    • FMHx: no hx similar disorder in other family members
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  • 366. CASE 14 Diagnosis? Unilateral Darier’s Disease (Keratosis Follicularis)
  • 367. Unilateral Darier’s Disease
    • Represents segmental manifestation of classic Darier’s disease
    • Genetic defect localized to chromosone 12q23-24.1 coding for SERCA2 (sarcoplasmic reticulum calcium ATPase)
    • Majority of cases autosomal dominant; however, sporadic cases occur
    • Segmental disease often lacks other associated features such as oral and nail findings
  • 368. Unilateral Darier’s Disease
    • Two clinical phenotypes:
      • Isolated segmental or linear disease (Type 1)
        • Segmental areas show same degree of severity as that seen in non-mosaic trait
        • Skin outside segmentally affected areas normal
        • Postzygotic mutation with somatic mosaicisim
        • More common (>50 patients reported)
      • Segmental disease in combination with diffuse distribution (Type 2)
        • Segmental areas more severe and superimposed on a milder diffuse form of same disease
        • Germline mutation present, but postzygotic mutation needed resulting in loss of heterozygosity
        • Rare (only 4 patients reported)
  • 369. Unilateral Darier’s Disease Histopathology
    • Acantholytic dyskeratosis:
      • Multifocal suprabasilar acantholysis
      • Dyskeratotic keratinocytes with formation of corps ronds and grains
      • Parakeratosis
  • 370. Unilateral Darier’s Disease Histopathology
    • Acantholytic dyskeratosis:
      • Multifocal suprabasilar acantholysis
      • Dyskeratotic keratinocytes with formation of corps ronds and grains
      • Parakeratosis
  • 371. Unilateral Darier’s Disease Treatment
    • Localized disease:
      • Topical retinoids
    • Severe generalized disease:
      • Oral retinoids
    • Hypertrophic lesions:
      • Excision
      • Dermabrasion
      • Laser ablation (Erbium:YAG)
    • Prevention of secondary bacterial or herpetic infection
  • 372.  
  • 373. CASE 15
  • 374. CASE 15
    • 32 y/o Cauc M presents with two month hx of diffuse non-pruritic eruption
    • Patient had been previously treated for “hives” by his PMD and was also given methylprednisolone and an oral in an emergency department subsequently
    • ROS: denied fever
    • PMHx: none per patient
  • 375.  
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  • 392. WARTHIN STARRY
  • 393.  
  • 394. CASE 15 Additional Laboratory Studies
    • CBC wnl
    • Initial RPR negative, Repeat one week later positive
    • HIV test positive
  • 395. CASE 15 Diagnosis? Secondary Syphilis
  • 396. Hoang et al. J Cutan Pathol . 31 (9): 595-9
  • 397.  
  • 398.