Pigmented Keratin Granuloma: A Rare Event

To The Editor: Epidermal cysts are one of the most common specimens encountered in daily surgical practice for skin excisions. Typically, their diagnosis poses no complexity, and reports are limited to reflecting some morphologic variations, such as the type of epithelial lining (tricholemal vs. infundibular, eg,) or the inflammatory response to the cyst. Among the morphologic variants, one of the less frequent is the pigmented epidermal cyst, which has been extensively documented in the literature.1–4 Even these pigmented cysts do not pose any diagnostic challenges beyond being a morphologic rarity. However, on occasion, if these pigmented cysts rupture, they can trigger a granulomatous response that is rich in melanin, characterized by a high number of histiocytes containing melanin pigment.5,6 In such cases, it can be difficult to identify remnants of the original cyst, and the main finding is a prominent pigmented foreign body giant cell granulomatous response to keratin.5 Pigmented keratin granuloma is rare in the literature (we have found only two previous cases)5,6 and, unlike the aforementioned situations, may present a diagnostic challenge even for experienced dermatopathologists. Therefore, we have found it interesting to present an additional example of this morphologic event. A 15-year-old girl was brought to the pediatric department by her parents, complaining of a leg lesion that had been present for one year. The girl had no other medical conditions and had a phototype IV. Upon examination, a greenish, atrophic plaque measuring 8 mm in diameter was observed on the right leg. With a suspected diagnosis of broken epidermal cyst, the lesion was excised. Histopathologic examination revealed a fragmented dermal cystic lesion (Fig. 1). The center of the cystic area was filled with laminated keratin and exhibited foci of calcification (Fig. 2A). In response to this material, a prominent giant cell granulomatous foreign body response was observed (Fig. 2B), composed of large histiocytes, many of which were multinucleated and intensely pigmented with a brown cytoplasmic pigment (Fig. 2C). Serial sections did not demonstrate the presence of “ghost cells” or basaloide component within nests, characteristic of pilomatricoma.FIGURE 1.: Panoramic low-power view, displaying a cystic formation containing laminated keratin content, surrounded by a foreign body histiocytic response, predominantly characterized by intensely melanin-pigmented giant histiocytes (Hematoxylin–eosin ×20).FIGURE 2.: A, Center of the cystic lesion with focal calcified keratin content (Hematoxylin–eosin ×100). B, Giant cell granulomatous foreign body response to keratin. Many histiocytes show pigmented cytoplasm (Hematoxylin–eosin ×100). C, Histiocytes with abundant brown cytoplasmic pigment (Hematoxylin–eosin ×100). D, Overlying epidermis of the lesion, showing acanthosis (Hematoxylin–eosin ×200).The overlying epidermis of the lesion showed acanthotic changes (Fig. 2D). Histochemical analysis demonstrated negative staining of the cytoplasmic pigment in histiocytes using the Perls technique (Fig. 3A) and positive staining using the Masson–Fontana technique (Fig. 3B).FIGURE 3.: A, Perls histochemical technique, demonstrating negativity of the brown pigment in the histiocytes (×200). B, Positivity of histiocytic pigment with Masson–Fontana histochemical technique (×200). C, Immunohistochemical staining against CD68, showing intense cytoplasmic positivity in the histiocytes (×100, counterstained with Giemsa). D, Immunohistochemical staining against S100, showing no expression in the pigmented histiocytes (×100, counterstained with Giemsa).Immunohistochemical examination confirmed the histiocytic nature of the pigmented cells, which were positive for CD68 (Fig. 3C) and negative for S100 (Fig. 3D). Consequently, the diagnosis was pigmented granuloma against keratin. The vast majority of epidermal cysts in individuals with low phototypes (fair skin) do not exhibit prominent pigmentation. However, the presence of melanin in cysts of individuals with high phototypes is not uncommon.1,4 Prominent pigmentation of the cyst wall in individuals with low phototypes has only been reported on rare occasions.4 When an epidermal cyst ruptures, it is common for extruded keratin to trigger a giant cell granulomatous foreign body response. However, the presence of abundant melanin within the histiocytes in such response is very unusual. In fact, we are only aware of two previous publications describing a similar response.5,6 In these cases, the morphologic picture may raise doubts about an atypical melanocytic tumor because of the size of the pigmented histiocytes. Basic immunohistochemical staining with histiocytic markers will help confirm their nature. Melanin supposedly originates from the pigmented lining epithelium of the ruptured cyst. Other pigmentary origins, such as iron or deposits because of antibiotics or other medications, should also be ruled out. Although some of these may stain with Masson–Fontana, they often contain iron as well and the pigment is usually not as abundant as in the case of granulomatous responses to pigmented cysts.7–13 The two previous similar studies we found5,6 do not report their patients’ phototype, but being from India suggests that both are likely a dark skin type. Our patient also had a high phototype IV. Although it is interesting that the phenomenon of pigmented granulomas against keratin is not as common in the literature, there are examples of histiocytic reactions with lower cytoplasmic amounts of melanin (melanophages) that are very common in inflammatory processes involving destruction of the basal layer of the epidermis. Furthermore, there is a phenomenon in oral pathology where pigmented granulomas are not as infrequent: pigmented periradicular cysts resulting from tooth extraction.14 In such cases, it is postulated that melanin may originate from melanocytes retained in the peridental area during their migration from the neural crest.14 In summary, we present a very rare phenomenon (the intense pigmentation of histiocytes in a foreign body granuloma against keratin) that should be known for its correct identification.