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Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla
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Non infectious&necrobiotic granulomatous diseases of the skin by M.Y.Abdel-Mawla

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To describe multiple faces of necrobiotic granulomas of skin

To describe multiple faces of necrobiotic granulomas of skin

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  • 1. NON- INFECTIOUS&NECROBIOTIC GRANULOMATOUS DISEASES OF THE SKIN M.Y.ABDEL-MAWLA
  • 2. ► Granulomatous reactions in the skin develop as an immune system response to an antigen, in which epithelioid macrophages and various inflammatory and immune cells congregate, often surrounded by fibrosis or a lymphocyte cuff ► They are classified as infectious or non-infectious ► There is a poor understanding of the inciting antigen, which may range from infectious (including live or dead microorganisms) to drugs (and/or their metabolites), or result from innate host pathology (e.g. connective tissue disease, vasculitis, or cancerous antigens). ► , it is important to acknowledge the proposed role for infection in the etiology of several of these conditions that are regarded as 'non-infectious' granulomatous disorders, such as a slow-growing infection, a post-infectious immunologic response, or presentation of granulomatous disease in the setting of infection.
  • 3. “ ” NON-INFECTIOUS GRANULOMATOUS DISORDERS ENCOMPASS A CHALLENGING GROUP OF DISEASES BOTH IN TERMS OF THEIR DIAGNOSIS AND IN COUNSELING PATIENTS REGARDING THEIR PROGNOSIS. IN ADDITION TO THE POSSIBLE SYSTEMIC CO-MORBIDITIES THEY MAY SUBSEQUENTLY ENCOUNTER. AN IMPORTANT SOURCE OF THIS CHALLENGE IS THE CLINICAL AND HISTOLOGIC OVERLAP AMONG THESE CONDITIONS (ALONG WITH THE POTENTIAL FOR MISDIAGNOSIS DUE TO THIS OVERLAP).
  • 4. NECROBIOSIS IS DEFINED AS THE PHYSIOLOGICAL DEATH OF A CELL . IT IS ASSOCIATED WITH ALTERATION OF COLLAGEN AND OR ELASTIC FIBRES IT IS IDENTIFIED BOTH WITH AND WITHOUT NECROSIS (PATHOLOGIC DEATH). IT IS ASSOCIATED WITH NECROBIOSIS LIPOIDICA AND GRANULOMA ANNULARE .
  • 5. NECROBIOSIS ►Necrobiosis refers to the degeneration of collagen fibres. ►Although this is easily noted in most necrobiotic dermatitides, it can be very subtle at times or even absent depending on the necrobiotic entity and the timing of the biopsy.
  • 6. STAINS HELPHUL IN NECROBIOSIS It is advisable to obtain three H&E levels and colloidal iron (Hale‟s stain for mucin). ► Elastochrome (elastic trichrome) could also be helpful in examining the vascular component of the lesion ► Special stains in granulomatous skin diseases, including necrobiotic dermatitides, to try to visualize any possible infectious agent. ► These stains include: periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) for fungal organisms, Zeil-Neilson (ZN) stain for acid-fast bacilli and Warthin-Starry silver stain for spirochetes
  • 7. ACCUMULATION OF BASOPHILIC FIBERS IN DERMIS, REFERRED TO AS BASOPHILIC DEGENERATION BASOPHILIC DEGENERATION
  • 8. 1. DEGENERATIVE CHANGE IN ELASTIC TISSUE. 2. DEGENERATION OF COLLAGEN FIBERS, WITH ALTERED STAINING PROPERTIES RESEMBLING ELASTIC TISSUE. 3-FORMATION BY FIBROBLAST-ACTIVATED ULTRAVIOLET OR MAST CELL MEDIATORS OF ABNORMAL FIBRES. ELASTOTIC DEGENERATION:elastoid degeneration.
  • 9. ELASTOTIC DEGENERATION(SYNONYM: ELASTOID DEGENERATION ► First of all either collagen fibres split into microfibrils and granular material, with subsequent appearance of the amorphous mass,. ► Amorphous mass is formed directly through the gradual loss of the matrix and membrane with subsequent confluence into future 'elastotic fibres'. At the amorphous stage, optically denser material appears..These are acquiring elastic stain properties. ► The elastic fibres were also often altered. When amorphous, their smaller size was helpful in distinguishing them from similarly altered collagen bundles.
  • 10. Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. Many of these disorders have significant associations with systemic diseases that impact the patient's overall prognosis Ten(10) non-infectious granulomatous conditions with implications for systemic disease: 1. granuloma annulare, 2. annular elastolytic giant cell granuloma, 3. necrobiosis lipoidica, 4. methotrexate induced accelerated rheumatoid nodulosis, 5. necrobiotic xanthogranuloma, 6. interstitial granulomatous dermatitis, 7. interstitial granulomatous drug reaction, 8. palisaded neutrophilic granulomatous dermatitis, 9. sarcoidosis. 10. metastatic Crohn disease.
  • 11. BLUE VS RED COLLAGENOLYTIC NECROBIOTIC GRANULOMAS ► A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers ► The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. ► Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red).
  • 12. BLUE CPLLAGENOLYTIC NECROBIOTIC GRANULOMAS ►These are the lesions of granuloma annulare , Wegener‟s granulomatosis, and rheumatoid vasculitis
  • 13. ETIOLOGY ►Human macrophage metalloelastases have been found in these lesions and may aid in the macrophage migration to these lesions. ► The activated histiocytes can surround the altered dermis in a palisading manner, potentially cordoning off harmful products of the inflammatory process such as immune complexes.
  • 14. WHY ARE THEY BLUE? ► A non-infectious granuloma can be centrally basophilic either due to mucin deposition or due to the presence of neutrophils/nuclear dust. ► If increased interstitial mucin is responsible for the blue color, as confirmed by either an Alcian blue or colloidal iron stain, one should consider the diagnosis of granuloma annulare (GA). ► If the basophilia of the central zone is due to the presence of neutrophils/nuclear dust,eitherWegener‟s granulomatosis (WG) or rheumatoid vasculitis enters the differential.
  • 15. THE „RED‟ COLLAGENOLYTIC GRANULOMAS ►The lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg–Strauss syndrome, and eosinophilic cellulitis (Well‟s syndrome).
  • 16. RED‟ COLLAGENOLYTIC GRANULOMAS:WHY ARE THEY RED? ► Eosinophilic staining of the necrobiotic area within a non-infectious granuloma can be due to hyalinized collagen, fibrin deposition, or degranulated eosinophils. ► If the collagen is hyalinized, the differential diagnosis of necrobiosis lipoidica (NL) vs. necrobiotic xanthogranuloma (NXG) exists. ► If the red color is due to fibrin deposition, then a rheumatoid nodule (RN) should be considered. ► If degranulated eosinophils are responsible for the color, then the lesions of Churg– Strauss syndrome (CSS) vs. eosinophilic cellulitis (EC) (Well‟s syndrome) should be considered.
  • 17. FEATURES OF NECROBIOTIC GRANULOMAS IN THE DERMIS ► - Located in the superficial and mid dermis. - Areas of necrobiosis surrounded by peripheral rim of histiocytes and lymphocytes. - Multinucleated giant cells (+/-) - Intervening areas of dermis between the necrobiotic granulomas is normal. - Central necrobiotic area contains abundant connective tissue mucins which is lightly basophilic in apperance. Mucin stains (Colloidal iron and alcian blue) are useful. - Small amounts of fibrin may be present as fibrillary eosinophilic material. - Perivascular infiltrate of lymphocytes in superficial & mid dermis. - Neutrophils and nuclear dusts are present in some cases. - Vasculitis may be present near foci of necrobiosis.
  • 18. Granulomas. A) Tuberculoid granuloma. (B) Sarcoidal granuloma. (C) Palisaded granuloma. (D) Caseation necrosis within a granuloma.
  • 19. GRANULOMA ANNULARE 1. GA is a benign inflammatory condition that often presents with a ring of multiple small, erythematous or flesh-colored, firm papules on the dorsal surface of the hands and/or feet. 2. Classified according to lesion morphology into subgroups: • localized, macular or patch, and atypical (consisting of perforating, subcutaneous, disseminated, palmar, photodistributed, or generalized forms). • Lesions are generally non-pruritic and self-limited, often resolving without treatment within 2 years, though a variety of treatments have been attempted. • A clinically similar, non-infectious granulomatous disease is annular elastolytic giant cell granuloma (AEGCG), which is often regarded as 'GA in sun- exposed areas.'
  • 20. ► Granuloma annulare is a common form of dermatosis in children and young adults. Lesions are typically found on the hands, the feet and the extensor surfaces of the limbs, and occasionally on the trunk. We report a case original in terms of its palpebral localization. ► CASE-REPORT: A 5 year-old girl consulted for papular lesions on the eyelids. The clinical examination revealed papules on the right lower eyelid measuring 8 mm, on the left lower eyelid measuring 5 mm and on the right upper eyelid measuring 3 mm. Laboratory tests including serum glucose, lipids and calcium as well as a complete blood count proved normal. Biopsy showed granulomatous lesions: a region of central necrosis surrounded by a palisade of inflammatory cells confirmed the diagnosis of granuloma annulare. The lesions disappeared in a few weeks without treatment.
  • 21. ►Histopathologic features OF GRANULOMA ANNULARE 1. “Interstitial GA” ► -May be early changes in other types of GA ► -Lymphocytes around small vessels, histiocytes between collagen bundles ► -Interstitial mucin (Alcian blue, colloidal iron positive, pH 2.5) in areas of histiocytes ► `Differential diagnoses: Morphea, reticular erythematous mucinosis (REM), interstitial pattern of mycosis fungoides 1. • Palisaded GA ► -Superficial and deep perivascular lymphocytic infiltrates ► -Interstitial histiocytes ► -Rings of histiocytes surrounding degenerating (and regenerating collagen) and mucin ► -A few neutrophils and some dust around necrotic venules in the centers of granulomas (rare) ► -Elastic tissue absent from centers of granulomatous foci
  • 22. ► Differential diagnosis: Necrobiosis lipoidica, rheumatoid nodule, palisaded neutrophilic and granulomatous dermatitis, others 3-• Deep GA ► -Large oval mass of histiocytes surrounding less cellular area ► -Degenerating collagen and mucin in the center, but more brightly eosinophlic than in conventional palisaded granuloma annulare ► Differential diagnosis: Rheumatoid nodule, phaeohyphomycotic cyst 4-• Actinic GA ► -Palisaded histiocytes around fibrosis ► -Giant cells commonly present ► -Elastotic material in cytoplasm of giant cells
  • 23. Granuloma annulare. (A) Pink papules annularly arranged. B) and (C) Palisaded granulomas with mucin in the center.. D) colloidal iron stain highlighting increased mucin.
  • 24. ANNULAR ELASTOLYTIC GIANT CELL GRANULOMA (AEGCG) A 'GA in sun-exposed areas AEGCG is caused by severe degeneration of skin elastic tissues in response to actinic injury While the clinical features of AEGCG and GA are similar and these conditions are often treated with the same approach, they are histologically distinct. AEGCG is characterized by a central zone of dermal atrophy that lacks elastic tissue; Additionally, AEGCG lesions do not show necrobiosis and palisading granuloma. An association of AEGCG with malignancy, (eg T-cell leukemia).
  • 25. PATCHY GRANULOMATOUS INFILTRATE IN RETICULAR DRMIS
  • 26. Gimesa statin showing consumption of elatic tissue in reticular dermis
  • 27. Hematoxylin-eosin stain (original magnification ×550) showing mild hyperkeratosis with deposition of pale eosinophilic degenerated elastin in the dermis. Note made of the multinucleated giant cells.
  • 28. Hematoxylin-eosin stain (original magnification ×550) showing degenerated elastin and multinucleated giant cells.
  • 29. Elastin van Gieson stain showing thinned out epidermis and extensive elastotic degeneration. Collection of histiocytes forming granuloma with phagocytosis of elastic fibers is also seen.
  • 30. Well-defined infiltrated plaque over forearm. Atrophic scarring can be appreciated at places
  • 31. NECROBIOTIC XANTHOGRANULOMA ► Necrobiotic xanthogranuloma with paraproteinemia (NXG) is a rare condition, but one that is important to recognize as it can maim patients, and some patients have died of its complications. ► Its name refers to its infiltrates of foamy histiocytes, zones of necrobiosis (degenerating and regenerating collagen) and frequent paraproteinemia. Despite the paraprotein, and the rare eventuation of myeloma in patients with NXG, it seems to be an inflammatory and not a neoplastic condition. ► Age: Middle-aged or elderly patients. ► Clinical presentation: Lesion presents as reddish, partly xanthomatous nodules or plaques. These are usually located around the periorbital area. Other sites include extremities & trunk. ► Frequently associated with paraproteinemia and lymphoproliferative diseases.
  • 32. NECROBIOTIC XANTHOGRANULOMA Clinical features: ► • Yellow plaques on limbs, with perioccular/periorbital lesions in most patients ► • Progression of lesions in some patients ► • Hyperlipidemia/hypercholesterolemia ► • Many patients diabetic ► • Serum paraprotein (usually IgG κ) ► • Loss of limbs or eye possible . ► Paraprotein levels play an important role in the pathogenesis of NXG because they might be autoantibodies that stimulate fibroblast proliferation and dermal macrophage deposition. ► The paraproteins cause a giant-cell inflammatory response after being complexed with lipids and deposited in skin. ► Activated monocytes accumulate lipids and are deposited in the skin, thereby eliciting a giant-cell foreignbody response
  • 33. HISTOPATHOLOGICAL FEATURES ►Extensive areas of hyaline necrobiosis surrounded by a palisade of histiocytes & multinucleated giant cells ; Large numbers of necrotic inflammatory cells in the reticular dermis ; Superficial and deep perivascular lymphoplasmacytic infiltrate ; Presence of foam cells, multinucleated giant cells (Touton & foreign body types), cholesterol clefts & extracellular lipid ; Lymphoid follicles may be present ; Extensive areas of fat necrosis in the subcutaneous tissue.
  • 34. HISTOPATHOLOGIC FEATURES ► • Infiltrate mid- and deep dermis, and both subcutaneous lobules and septa ► • Superficial and deep perivascular infiltrates of lymphocytes and plasma cells, sometimes very dense ► • Lymphoid follicles ► • Palisaded foamy histiocytes surrounding homogeneous eosinophilic material ► • Foamy histiocytes and Touton giant cells in subcutis (“Touton cell panniculitis”) ► • Giant cells with scalloped margins ► • Cholesterol clefts surrounded by rings of foamy histiocytes (cholesterol granulomas)
  • 35. NECROBIOTIC XANTHOGRANULOMA Histopathology:multiple giant cells including Tuton cells
  • 36. ► Successful IVIg treatment of paraproteinemiaassociated dermatoses, such as scleromyxedema, has been . ► , IVIg showed a striking therapeutic effect on NXG. Given the association of NXG with IgG- monoclonal gammopathy (more often IgG- than IgG-) and with multiple myeloma
  • 37. NECROBIOTIC XANTHOGRANULOMA VS NECROBIOSIS LIPODICA ► NXG is often mistaken for NLD, as both can present as yellow plaques on the limbs of diabetic patients. ► Cholesterol clefts surrounded by foamy histiocytes are practically pathognomomonic of the condition(NXG) . ► Cholesterol clefts were present in specimens of NLD in one study, but not surrounded by foamy macrophages and Touton giant cells.
  • 38. NECROBIOSIS LIPODICA ► Necrobiosis lipoidica (NL), originally known as necrobiosis lipoidica diabeticorum, is a disorder of collagen degeneration with a granulomatous response and thickening of blood vessels. Diabetes mellitus is present in more than half the patients with necrobiosis lipoidica. ► Age & sex: Average age of onset is 30 years (may occur at any age) and females are commonly affected. ► Site: Most cases are located on the leg specially above the tibiae, but may also occur on the face, scalp, forearm and trunk. ► Clinical presentation: Lesions may be single but multiple lesions are more common. NL may present as red papules which may enlarge to form patches or plaques with an atrophic yellowish-brown and slightly depressed center. The lesions may resolve spontaneously or become persistent chronic lesions which may ulcerate. Clinical features- ► • Most lesions bilaterally on shins ► • Early lesions are red papules with sharp borders ► • Later, yellow, hard atrophic plaques ► • 60% have frank diabetes, another 20% abnormal glucose tolerance o
  • 39. HISTOPATHOLOGICAL FEATURES ► Necrobiotic granuloma and inflammatory infiltrate: ► Full thickness of the dermis is involved with extension into the subcutis. ► The inflammatory cells are composed of histiocytes, lymphocytes, plasma cells and occasional eosinophils are arranged in two or three tiers. These are aligned parallel to the skin surface. ► There are several layers of necrobiosis within the reticular dermis. Necrobiotic areas are rimmed by histiocytes and multinucleate Langhans or foreign body giant cells. ► The necrobiosis is irregular and less complete than in granuloma annulare. ► ( Note: Palisaded granuloma in necrobiosis lipoidica- Early lesions show prominent collagen degeneration. Late lesions show crowded and thickened collagen bundles. ) ► The intervening areas of the dermis are also abnormal. Lymphoid cell aggregates with germinal centers may be present. ► Abnormalities present in the reticular dermis are also present in the septa of the subcutaneous tissue (septal panniculitis with granulomatous inflammation). ► Vascular changes: ► Vascular changes are more prominent in diabetic patients. ► Superficial and deep perivascular inflammatory infiltrate. ► Plasma cells are conspicuous. ► Superficiall vessels are telangiectatic & increased in number. ► Deeper vessels may show endothelial swelling. ► Lymphocytic vasculitis may be present. ► Epithelioid granulomas within or adjacent to the vessel wall. ► Other features: Intradermal nerves are reduced in number. ► Old and atrophic lesions show dermal fibrosis and thickened septa of the subcutaneous fat . ► Lipid in the upper part of the dermis can be demonstrated by Sudan black and oil red O stain. ► Stains for mucin (colloidal iron or alcian blue) are usually negative.
  • 40. PALISADED NEUTROPHILIC AND GRANULOMATOUS DERMATITIS (PNGD ► A disease spectrum described in patients with systemic diseases of various kinds. ► Terms such as rheumatoid papules, Churg-Strauss granuloma, extravascular necrotizing granuloma and Winkelmann granuloma also refer to this condition. ► The main clinical presentation is of small, umbilicated papules on the dorsal aspects of joints, esp. those of the fingers, elbows and knees. ► The range of systemic diseases in patients with PNGD includes patients with: ► 􀂃 Systemic lupus erythematosus ► 􀂃 Rheumatoid arthritis (incl. seronegative cases) ► 􀂃 Wegener‟s granulomatosis ► 􀂃 Lymphoma/leukemia ► 􀂃 Inflammatory bowel disease ► 􀂃 Systemic
  • 41. PALISADED NEUTROPHILIC AND GRANULOMATOUS DERMATITIS ► The salient histopathologic features differ for each stage of PNGD: ► Early: ► 􀂃 Fibrin around vessel walls ► 􀂃 Neutrophils and abundant nuclear debris around vessels around fibrin ► Fully developed: ► 􀂃 Palisaded histiocytes around neutrophils and their debris ► 􀂃 Thick, but discolored collagen bundles ► 􀂃 Evidence of vasculitis, sometimes ► Late: ► 􀂃 Palisaded histiocytes around zones of fibrosis with few neutrophils ► 􀂃 No vasculitis
  • 42. HISTOPATHOLOGICAL FEATURES ► Early lesions have increased dermal spindle cells ► Increased mucin with thin elastic fibres ► Later lesions have more epithelioid or stellate cells that may extend into septa in subcutaneous fat ► Thick collagen bundles ► The spindle cells are fibrocytes that are positive immunohistochemically with both CD34 and mprocollagen
  • 43. EARLY PALISADED NEUTROPHILIC AND GRANULOMATOUS DERMATITIS. THERE IS A PALISADE OF HISTIOCYTES AROUND CENTRAL FOCUS OF NECROTIC COLLAGEN.
  • 44. Late palisaded neutrophilic and granulomatous dermatitis/interstitial granulomatous dermatitis wit arthritis. The central necrosis has disappeared to leave a diffuse granulomatous dermatitis. In contrast to granuloma annulare, there are neutrophils, no collections of mucin and the process is diffuse.
  • 45. “INTERSTITIAL GRANULOMATOUS DRUG ERUPTION ► large interstitial histiocytes, and a more subtle palisaded pattern. It presents with dusky erythema in flexural areas. There are small foci in which degenerated neutrophils and/or eosinophils are present ► Palisaded foci surrounding degenerated neutrophils and eosinophils are not yet reported, but histiocytes form rosettes that surround and adhere to thick collagen bundles, demarcated from the rest of the dermis by clefts.
  • 46. PALISADED GRANULOMATOUS REACTIONS TO FOREIGN MATERIAL ►Histiocytes can be radially arranged around a variety of foreign substances, including suture material, beryllium, and injectable (bovine) collagen. ►The mechanism by which the dermis is altered in some of these reactions is unclear.
  • 47. RHEUMATOID NODULE(RN) ► Clinical features ► • Symmetrical papules and nodules ► • Usually subcutaneous, sometimes fixed to tendons ► • Skin color unchanged, sometimes yellow (simulating xanthomas) ► • Extensive disease with joint destruction (rheumatoid nodulosis) ► Histopathologic features ► • Large oval mass in deep dermis/subcutis ► • Palisaded histiocytes surrounding degenerated collagen, large amounts of fibrin, neutrophils and nuclear dust ► • Mucin scant or absent ► • Vasculitis in adjacent vessels rarely . ► The vast majority of diagnoses of RN in well children are misdiagnoses of deep GA!
  • 48. WEGENER‟S GRANULOMATOSIS(WG) Granulomatous ulceration of the mucous membranes that includes chronic sinusitis, nasal crusting, and bleeding ► Gingivitis called „strawberry gums‟, ► Accompanied by a slow loss of nasal cartilage leading to the „saddle nose‟ deformity. ► A fulminant process with acute respiratory symptoms, often with alveolar hemorrhage ► Cardiac involvement with necrotizing coronary vasculitis and pancarditis ► Constitutional symptoms including fever, weight loss, anorexia, and arthralgia, as well as cough . ► The most common cutaneousWGlesions are clinically 1. papulonecrotic lesions or palpable purpura, 2. usually on the extremities. 3. Less common lesions include vesicles, petechiae, subcutaneous nodules, and frank ulcerations with thrombosis and necrosis. ► An acneiform presentation has been reported in children.chest and pain.
  • 49. HISTOPATHOLOGIC PATTERNS OF WEGNER GRANULOMATOSIS ►The most common histologic pattern seen within WG lesions of the skin is that of a necrotizing vasculitis ►Palisading necrotizing granuloma :Focal necrobiosis with peripheral palisading, ►Granulomatous vasculitis, No mucin/fibrin ►Lymphomatoid granulomatosis-like pattern:vasculitis infiltrated with atypical lymphocytes, but not true lymphoma
  • 50. RHEUMATOID NODULE
  • 51. RHEUMATOID NODULE
  • 52. RHEUMATOID VASCULITIS Palisading granuloma due to leukocytoclastic vasculitis .
  • 53. CHURG–STRAUSS SYNDROME ► It has three distinct phases. The first clinical phase of CSS is the prodromal or allergic ► phase,:asthma, which may or not be preceded by allergic rhinitis. Nasal obstruction, recurrent sinusitis, and nasal polyposis frequently develop. ► The second clinical phase of CSS features marked peripheral eosinophilia and eosinophilic infiltrates of the respiratory and intestinal tracts (eosinophilic gastroenteritis.):Abdominal pain is common and may reflect bowel perforation, peritonitis, intestinal obstruction, mesenteric vasculitis, or cholecystitis ► The third phase of CSS development can include a neuropathy ► skin lesion(Churg–Strauss granuloma)::a papule or subcutaneous nodule:erythematous orviolacious, and are often symmetrically distributed. ► They are persistent and tender, often become crusted or ulcerated, and resolve with scarring within 2–3months. These lesions usually occur on the extremitiesand scalp, and less commonly on the trunk, with the most common sites located over pressure points, especially the elbows, fingers, and thumbs.
  • 54. CHURG–STRAUSS GRANULOMA
  • 55. HISTOPATHOLOGY ► The palisading Churg–Strauss granuloma consists of leukocytoclastic vasculitis and degeneration of the surrounding collagen, with an extravascular palisading granulomatous reaction, consisting of mononuclear cells, macrophages, and eosinophils around the necrobiotic collagen ► The degenerated collagen becomes admixed with polymorphonuclear leukocytes and leukocytoclastic debris ► The palisading granulomatous infiltrate probably develops due to an influx of eosinophils which degranulate and develop pyknotic, fragmented nuclei. ► fibrinoid swelling and increased degeneration of the collagen fibers, with the eventual destruction of the fibers. ► Macrophages infiltrate the area, palisading around the central necrotic core, and Langhans or foreign body-type giant cells appear
  • 56. CHURG–STRAUSS GRANULOMA Palisading granulomatous infiltrate surrounding degenerated collagen
  • 57. EOSINOPHILIC CELLULITIS (WELL‟S SYNDROME) ► Patients can become febrile and develop peripheral eosinophilia ► typically erupts suddenly as single or multiple edematous, erythematous, well-defined annular plaques on a limb that often initially appear urticarial ► lesions include papules, vesicles, poorly demarcated erythematous plaques, or nodules. ► The subsequent edema may become so severe as to generate bullae. Although the affected area clinically resembles a bacterial cellulitis, the skin is cool to the touch ► As the acute edema and erythema subsides, the affected area becomes indurated and acquires a bluish or greenish gray color, clinically resembling morphea ► The cause: a hypersensitivity reaction to some triggering event including insect bites, fungal infections, herpes simplex virus flares,,underlying hematologic disorders, ,oxocara canis infections, or drug hypersensitivities
  • 58. HISTOPATHOLOGY ► The biopsy of a newly developing EC lesion shows a papillary dermis that is markedly edematous with overlying spongiosis and intraepidermal spongiotic vesicles. ► The dermis is heavily infiltrated with eosinophils ► As the lesion develops, eosinophils degranulate and then degenerate. Fragments of the degenerated eosinophils and their expelled granules are deposited onto the surrounding collagen fibers, producing „flame figures‟ ► Older lesions show a granulomatous infiltrate comprised of large histiocytes and giant cells that surround the flame figures
  • 59. EARLY PHASES OF WELLS DISEASE Eosinophilic cellulitis; early edema and eosinophilic infiltrate
  • 60. LATE PHASE OF WELLS DISEASE Eosinophilic cellulitis; late granulomatous infiltrate around degenerated collagen and eosinophilic granules
  • 61. THANK YOU

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