Histopathologic Patterns Associated with External Agents

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A large list of foreign substances may penetrate the skin due to both voluntary and involuntary reasons.
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Histopathologically, most of these substances induce a foreign-body granuloma with multinucleate giant cells.
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The microscopic morphology of the external particles is helpful in recognizing specifically the involved foreign substance.

Key Points

A large number of foreign substances may penetrate the skin for both voluntary and involuntary reasons. The voluntary group includes the particulate materials used in tattoos and cosmetic fillers, whereas the involuntary group is almost always caused by accidental inclusion of external substances secondary to cutaneous trauma. Table 1 summarizes the most common foreign bodies found in cutaneous biopsies. Histopathologically, most of these substances induce a foreign-body granuloma with multinucleate giant cells, involving the dermis, and often extend to the subcutaneous tissue. Sometimes secondary infection occurs in the preexisting foreign-body granuloma. The foreign substance may or may not be refringent when sections are examined under polarized light. Cutaneous foreign-body granulomas may also develop secondary to endogenous material that has become altered in such a way that it is recognized as a foreign substance, as in the case of calcium deposits, urate, oxalate, keratin, and hair shafts. These endogenous materials are not discussed in this article. Herein, the authors focus on the histopathologic findings seen in cutaneous reactions to exogenous agents, with special emphasis on the microscopic morphology of the external particles in recognizing specifically the involved substance (something that is becoming increasingly important in the event of litigation).

Table 1

Foreign substances that may be found in the skin

Substance	Histopathology
Tattoo pigments	Sarcoidal or foreign-body granulomas. Pseudolymphoma. Pigmented granules of several colors according to the composition of the tattoo
Cosmetic fillers	Foreign-body granulomas containing particles of variable morphology (see Table 2 )
Drugs and medications	Tuberculoid or foreign-body granulomas. Ferruginated collagen fibers with Monsel solution
Drugs and medications	Banana-like collagen fibers in exogenous ochronosis. Foreign-body granuloma with numerous lymphoid aggregates at the site of injection of aluminum-adsorbed vaccines. Mostly lobular panniculitis at the site of injection of several drugs
Silica	Sarcoidal granulomas containing birefringent particles
Beryllium	Sarcoidal granulomas with central fibrinoid necrosis
Zirconium	Sarcoidal granulomas
Glass	Foreign-body granulomas containing birefringent particles
Starch	Suppurative granulomas
Talc	Suppurative granulomas containing Maltese-cross birefringent granules
Graphite	Foreign-body granuloma around black polygonal particles with birefringent borders
Paraffin	Mostly lobular panniculitis with Swiss-cheese appearance
Shrapnel	Foreign-body or suppurative granulomas
Suture material	Foreign-body granuloma. Each type of suture shows a characteristic appearance and birefringence pattern
Arthropods	Dermal eosinophilic granulomas
Sea urchin spines	Sarcoidal granulomas
Cactus spine	Suppurative granulomas
Vegetable oil	Suppurative granulomas
Wood splinter	Suppurative granulomas
Mineral oil	Sclerosing lipogranulomas
Food particles	So-called pulsed granulomas containing small hyaline rings. Sometimes hyaline perivascular rings (hyaline angiopathy)