Section 2 -

Granulomatous Dermatitis Clifton R. White, Jr. Professor of Dermatology and Pathology Oregon Health and Sciences University Portland, Oregon

Granulomatous Dermatitis Case Histories Case 1: A 60-year old woman developed periorbital papules, one of which was biopsied by her left medial canthus. The patient presented with presumed sarcoidosis although a broncoscopy procedure had failed to result in a tissue diagnosis. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 2: A 58-year old female with a history of pulmonary sarcoid twelve years ago, diabetes, and "fibromyalgia" recently developed indurated subcutaneous plaques which were erythematous on her arms and legs. She also had fatigue and fever. The clinician considered subcutaneous sarcoidosis, morphea, and panniculitis. Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3: A 47-year old woman presented with papules around her left knee. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4: A 36-year old man presented for violaceous annular plaques around his right knee and both elbows and forearms. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 5: A 59-year old woman developed a reddish yellowish telangiectatic plaque with no scale on her anterior lower leg. Case 5 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 6: A 77-year old man presented with a past history of multiple nodules of varying size scattered around his trunk and face. Case 6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 7: A 48-year old man had a biopsy from his knee of a yellow red nodule. Case 7 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 8: A 7-year old girl developed a papule on her right lower eyelid. Case 8 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Granulomatous Dermatitis As with all patterns of inflammation, nodular and diffuse dermatitis represent continua rather than discrete entities. For example, as you peruse examples of diseases in nodular and diffuse categories, some of the same conditions are present in each group. Diagnosing nodular and diffuse dermatitis rests first on accurate recognition of the pattern, and second by determining the answer to the key question in this algorithm what is/are the predominant cell type(s) present within the nodular or diffuse infiltrate? An appropriate answer allows one to precede correctly down the leg of the algorithm. Nodular and diffuse dermatitis represent a large number of dermatologic conditions. For today's discussion we will concentrate on nodular and diffuse dermatitis consisting predominantly of histiocytes (granulomatous dermatitis). Granulomatous dermatitis can be broadly classified as conditions within which tissue monocytes/macrophages, i.e., "histiocytes", are the predominant inflammatory cell in some foci. In granulomatous inflammation, epithelioid histiocytes are present. Epithelioid cells may be defined as histiocytes with oval vesicular nuclei surrounded by abundant granular cytoplasm with poorly defined cell borders which appear to touch one another. Because of abundant pale staining cytoplasm in epithelioid histiocytes, the infiltrate has a pale appearance at scanning magnification which is a clue to its granulomatous nature. Epithelioid histiocytes are often arranged in a closely packed accumulation termed a tubercle. The term "granuloma" is often used as a synonym. Granulomatous inflammation may be distributed in nodular or diffuse fashion. At scanning power, nodular granulomatous dermatitis presents in one of four patterns. I. Tubercles or granulomas, with few to no surrounding lymphocytes ("naked" or sarcoidal granuloma). II. Tubercles admixed with lymphocytes and occasionally with central necrosis (tuberculoid granulomas). III. Palisaded granulomatous in which the epithelioid histiocytes are arranged individually between collagen bundles around a central anuclear region characterized by mucin deposition, collagen degeneration and sclerosis, and fibrinoid deposition ("necrobiosis"). IV. Suppurative granulomas consisting of admixtures of neutrophils and histiocytes in the absence of tubercle formation. Considerable overlap may occur amongst these artificial designations although this algorithmic approach has utility in developing a differential diagnosis. In general, all granulomatous infiltrates require the exclusion of infectious agents and foreign material, regardless of the pattern, through the judicious use of special stains for micro-organisms and examination of tissue with polarizing lenses. Rarely, more sophisticated techniques may be required such as spectro-photometric or X-ray analysis. TABLE I: Nodular Granulomatous Dermatitis I. SARCOIDAL II. TUBERCULOID III. PALISADED IV. SUPPURATIVE (Foreign Body Granuloma) Lichen nitidus Lichen striatus Sarcoidosis Beryllium Zirconium Silica Tattoo Granulomas Cutaneous Crohn's disease Granulomatous cheilitis (Miescher- Melkersson- Rosenthal syndrome) Granulomatous rosacea Tuberculoid and dimorphous leprosy Tuberculosis (primary cutaneous, lupus vulgaris, scrofuloderma, and miliary types) Chronic cutaneous leishmaniasis Tuberculoid and dimorphous leprosy Late secondary and tertiary syphilis Brucellosis Granulomatous rosacea Post-herpetic Granulomas Granuloma annulare Necrobiosis lipoidica Necrobiotic xanthogranuloma Granuloma disciformis of the face (Miescher's granuloma) Palisaded neutrophilic and granulomatous dermatitis Rheumatoid and pseudo-rheumatoid nodule Gout Ruptured follicular cyst Metals (mercury, carbon) Vegetable materials (splinters, suturescactus spines), Silica Starch Drug injections (Talwin; morphine) Bacterial; Mycobacterial; Actinomycotic; Deep fungal; Yeast; Algal; Amoebic Infections I: Sarcoidal Lichen Nitidus Histologic features: Tiny papules characterized by inflammation confined to a single enlarged dermal papilla Nodular collections of epithelioid histiocytes often forming a small tubercle Variable numbers of lymphocytes intermixed with the epithelioid histiocytes Parakeratosis Thinned epidermis with vacuolar change Lichen Striatus Histologic features Multiple patterns of inflammation Spongiotic, psoriasiform, lichenoid, and nodular Nodular aggregates of epithelioid histiocytes in dermal papillae Scale-crust Spongiosis Sarcoidosis Histologic features: Nodular aggregates of epithelioid histiocytes (tubercles) involving the dermis and often subcutaneous lobules Few lymphocytes admixed with the histiocytes ("naked tubercle"). Occasional multinucleated histiocytes Rare inclusions (asteroid body; Schaumann body) Occasionally tubercles confined to the subcutaneous fat (Darier-Russy sarcoid) Various foreign body granulomas (beryllium, zirconium, silica) histologically indistinguishable from sarcoidosis Cutaneous Crohn's Disease Histologic features: Sarcoidal granulomas within the dermis mirroring histologic findings in the bowel. Granulomatous Cheilitis (Miesher-Melkersson-Rosenthal Syndrome) Histologic features: Granulomatous inflammation often times inconspicuous or absent Predominantly a superficial and deep mononuclear infiltrate of plasma cells and lymphocytes Occasional sarcoidal tubercles II: Tuberculoid Lupus Vulgaris Histologic features: Pseudocarcinomatous epidermal hyperplasia, often Dense infiltrate of lymphocytes and plasma cells Tuberculoid granulomas throughout the dermis Mycobacterial organisms typically inapparent or not demonstrable Tuberculoid Leprosy Histologic features: Elongated tubercles scattered throughout the dermis, perhaps reflecting peripheral nerve involvement. Characteristic perineural inflammation Mycobacterial organisms absent or few in number Granulomatous Rosacea Histologic features: Tubercles juxtaposed between and around vellus follicles. Central necrosis often present, reflecting adjacent ruptured follicle III: Palisaded Granuloma Annulare Histologic features: Nodular infiltrates of epithelioid histiocytes often separated by uninvolved dermis Rare multinucleated epithelioid histiocytes Histiocytes arranged between collagen bundles in palisaded fashion classically Interstitial histiocytic distribution more common Mucin deposited between degenerated collagen bundles centrally within the histiocytic infiltrate (colloidal iron, Alcian Blue, etc., positive) Perivascular infiltrates of lymphocytes Necrobiosis Lipoidica Histologic features: Early on, indistinguishable from granuloma annulare Well developed lesions characterized by nodular to diffuse histiocytic infiltrates Histiocytes arranged between collagen bundles in palisaded fashion often given a "layered" appearance. Numerous multinucleated epithelioid histiocytes Involvement of both the dermis and subcutaneous fat septae (dermatitis and septal panniculitis) Histiocytes arranged around sclerotic collagen (no mucin deposition) Perivascular infiltrates of lymphocytes and plasma cells Necrobiotic Xanthogranuloma Histologic features: Diffuse infiltrate of the dermis extending into the subcutaneous fat Densely cellular in contrast to necrobiosis lipoidica and granuloma annulare Numerous multinucleated epithelioid histiocytes arranged in palisaded fashion Some multinucleated histiocytes with many nuclei ("bizarre giant cells") Foamy histiocytes and extracellular lipid (cholesterol clefts) Perivascular lymphocytes and plasma cells Associated with monoclonal gamapathy usually IV: Suppurative (Foreign Body) Follicular Cyst, Ruptured Histologic features: "Non-organized" nodular infiltrates of neutrophils and epithelioid histiocytes, primarily multinucleated Epithelial cyst wall may not be present Cornified cells within histiocytic cytoplasm a clue to the diagnosis Silica granuloma Sarcoidal granulomatous pattern "Knife marks" a clue to the presence of silica particles Examination with polarizing lenses necessary TABLE II: Diffuse Granulomatous Dermatitis I. NEUTROPHILS PROMINENT (SUPPURATIVE) II. LIPOPHAGES PROMINENT (FOAMY HISTIOCYTES) III. VIRCHOW CELLS IV. LANGERHANS' CELLS Often with peudocarcinomatous hyperplasia. Botryomycosis Rhinoscleroma Actinomycosis Chromomycosis Coccidioidomycosis Sporotrichosis Mycetoma Follicular occlusion tetrad (acne conglobata, hidradenitis suppurativa, dissecting cellulitis of the scalp, and pilonidal sinus) Xanthelasma Xanthomas (eruptive, tuberous, tendinous, planar) Xanthogranuloma Verruciform xanthoma Reticulohistiocytic granuloma Multicentric reticulohistiocytosis Benign cephalic histiocytosis Lepromatous and dimorphous\ leprosy Langerhans cell histiocytosis (Letterer-Siwe/Hand-Schuller-Christian/eosinophilic granuloma I: Diffuse Granulomatous Dermatitis Chromomycosis Histologic features: Pseudocarcinomatous hyperplasia Diffuse infiltrate throughout the dermis of neutrophils and multinucleated epithelioid histiocytes Organisms typically located within the cytoplasm of multinucleated histiocytes or within neutrophil collections Yeasts with characteristic brown pigment (copper pennies, medlar bodies) Coccidioidomycosis Histologic features: Pseudocarcinomatous epidermal hyperplasia Diffuse suppurative granulomatous dermatitis Characteristic large "mother" spore containing numerous tiny "daughter" spores Follicular Cyst, Ruptured Histologic features: Diffuse suppurative granulomatous dermatitis Laminated to basketweave cornified cells within the cytoplasm of multinucleated histiocytes a clue to the diagnosis Eruptive Xanthoma Histologic features: May be strikingly similar in appearance to granuloma annulare Diffuse infiltrate of histiocytes. Varying numbers of foamy histiocytes and epithelioid histiocytes Extracellular lipid common Xanthogranuloma Histologic features: Dome shaped nodule characteristically Diffuse infiltrate consisting predominantly of histiocyte Many histiocytes multinucleated including Touton and Langhans types Numerous mononuclear histiocytes, some with foamy cytoplasm Admixture of lymphocytes and plasma cells Reticulohistiocytic Granuloma Solitary and Multiple (Multicentric) Histologic features: Dome shaped nodule Diffuse infiltrate of histiocytes, most of them mononuclear Occasional multinucleated histiocytes Characteristic opaque "ground glass cytoplasm" Lepromatous Leprosy Histologic features: Diffuse infiltrate of foamy histiocytes Sparring of the upper papillary dermis "Foamy" histiocytes with amphophilic granular "inclusions" (Globi) Numerous organisms, individually and in collections (Globi) on Fite Faraco stain Langerhans Histiocytosis Letterer-Siwe/Hand-Schuler-Christian/Eosinophilic Granuloma Histologic features: Band-like to diffuse distribution in the upper dermis Epidermal involvement by histiocytes common Characteristic curved nucleus (reneform, coffee bean) Pale cytoplasm Occasional multinucleated histiocytes Admixture of eosinophils CD1a and S-100 positive; CD68 positive occasionally