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Pathology of Granuloma


Dr Sampurna Roy MD

Dermatopathology Quiz Case 210

Diagnosis: Granuloma Annulare

Dermatopathology Quiz Case 184

Diagnosis: Granuloma Annulare

Path Quiz Case 54: History and images:

Diagnosis: Subcutaneous Granuloma Annulare

January 2016


Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)



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Granuloma annulare (GA) is a benign inflammatory, self-limiting granulomatous dermatoses that is seen in both adults and children

Females are more commonly affected than males.

The lesions may involve skin and/or subcutaneous tissue.

The etiology of GA is unknown.

The lesions could  be related to insect bites, sun exposure, viral infections, diabetes, thyroiditis, immunoglobulin-mediated vasculitis, and certain medications such as antibiotics, antiinflammatory agents and oral contraceptives.

Cases have also been reported in patients with AIDS, sarcoidosis, hepatitis C infection, Hodgkin's and non Hodgkin's lymphoma, metastatic adenocarcinoma and granulomatous mycosis fungoides.

Clinical variants:

(1) Localized - Children & young adults. Papules & annular or arciform plaques.
Site: Hands, feet, arms & legs.

(2) Generalized - Middle aged and elderly patients. Multiple macules, papules or nodules.
Site: Trunk & limbs.

(3) Perforating -  Middle aged & elderly females. Papules & annular plaques. Scaling & crusting with central umbilication may be present.
Site: Dorsa of the hands and feet.

(4) Subcutaneous or deep form - Children & young adults. Solitary or multiple nodules (a few millimeters to several centimeters in size).
Site:  Lower extremities, dorsa of the hands & feet, buttock and scalp.

Histological patterns in Granuloma Annulare:

1. Necrobiotic granuloma

2. Interstitial or 'incomplete' form - Most common

3. Granuloma of sarcoidal or tuberculoid type: Rare

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.

Differential diagnosis: 

Necrobiosis Lipoidica:

Multilayered necrobiosis (stacks of plates) with open ends.

Numerous plasma cells.

Thickened collagen bundles within palisaded granuloma.

Diffuse process present throughout the reticular dermis.


Features of interstitial or 'incomplete' form of Granuloma Annulare:

-  Should be assessed under low power.

- "Busy dermis" - increased number of inflammatory cells in the dermis separated by connective tissue mucin.

-  Infiltrate composed of lymphocytes and histiocytes.

-  Inflammatory cells are noted around blood vessels and between collagen bundles.

-  No well-defined areas of necrobiosis

Differential diagnosis: 

(1)  Interstitial granulomatous drug reaction:  Eosinophils (+) , lichenoid changes at dermoepidermal junction , true necrobiosis is rarely noted .

(2)  Interstitial granulomatous dermatitis :  Neutrophils, neutrophil fragments, histiocytes, lymphocytes & eosinophils are present , palisades of histiocytes around basophilic collagen fibres.

Changes may involve the full thickness of the dermis.

Features of Subcutaneous Granuloma Annulare-(Pseudorheumatoid Nodule):     

- Located in the deep dermis, subcutis and rarely deep soft tissue.

- Area of necrobiosis is larger than the superficial type.

- Granulation tissue and lymphoid aggregates may be present near palisaded granuloma.

- Eosinophils are more common in this variant.

Differential diagnosis:  Rheumatoid Nodule  :  Rheumatoid nodule and subcutaneous granuloma annulare. A comparative histologic study.Am J Dermatopathol. 1988 ;10(1):1-8.

Necrobiotic foci contain abundant fibrin. Degenerated bundles of collagen (+/-).  Palisade of elongated histiocytes.

Features of disseminated form of granuloma annulare:

- Poorly formed granulomatous foci in the papillary dermis.

- Necrobiosis is not prominent.

Differential diagnosis: Lichen Nitidus : Claw-like acanthotic elongation of rete-ridges at the periphery of the lesion is absent in GA.

Non-necrobiotic sarcoidal or tuberculoid type of GA:  

Rare variant.

Dermal mucin and eosinophils help in distinguishing this lesion from sarcoidosis.

Perforating GA: 

Epidermal perforation connected to the underlying necrobiotic granuloma.


Further reading:

Evolution of Granuloma Annulare to Mid-dermal Elastolysis: Report of a case and review of the literature.

Generalized granuloma annulare after bacillus Calmette-Guérin vaccination, clinically resembling papular tuberculid.

Periocular Granuloma Annulare: A Case Report and Review of Literature.

Trauma-related papular granuloma annular.

Perforating granuloma annulare mimicking papulonecrotic tuberculid.

Necrobiotic Granulomatous Tattoo Reaction: Report of an Unusual Case Showing Features of Both Necrobiosis Lipoidica and Granuloma Annulare Patterns.

Granuloma annulare mimicking multicentric reticulohistiocytosis.

Detection of factor XIII-A is a valuable tool for distinguishing dendritic cells and tissue macrophages in granuloma annulare and necrobiosis lipoidica.

Granuloma annulare as a possible new adverse effect of topiramate.

Localized interstitial granuloma annulare induced by subcutaneous injections for desensitization.

Pseudorheumatoid nodules in adults: a juxta-articular form of nodular granuloma annulare.

Bilateral and subcutaneous palmar nodules in a 2-year-old child suggesting deep granuloma annulare.

Collagenolytic (necrobiotic) granulomas: part 1--the "blue" granulomas.

The spectrum of primary cutaneous elastolytic granulomas and their distinction from granuloma annulare: a clinicopathological analysis.

Subcutaneous granuloma annulare in an adult.

Subcutaneous Granuloma annulare in childhood: clinicopathologic features in 34 cases.  

A case of recurrent disseminated granuloma annulare.  

Patch granuloma annulare: clinicopathologic study of 6 patients.

Deep granuloma annulare (pseudorheumatoid nodule) in children: clinicopathologic study of 35 cases. 

Subcutaneous Granuloma annulare: a review of 47 cases.

Granuloma annulare: an immunohistochemical study. 

Generalized granuloma annulare: histopathology and immunopathology. Systematic review of 100 cases and comparison with localized granuloma annulare.

Granuloma annulare: identification of cells in the cutaneous infiltrate by immunoperoxidase techniques.

Histologic, ultrastructural and histochemical studies of granuloma annulare. 

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