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Dermatopathology: Practical & Conceptual

October – December 2010 | Volume 16, No. 4

Keratoacanthoma metastatic to the parotid gland

Böer, Almut; Broyer, Jasmin

Introduction

Keratoacanthoma is a keratinocytic neoplasm which has been subject of controversy over the last decades. Because of its tendency to regress spontaneously without any treatment, for a long time it was considered to be a pseudomalignancy. [1] In contrast, cytopathologic features of keratoacanthoma are identical to those of a well-differentiated squamous cell carcinoma. Therefore, it has been suggested that keratoacanthoma is just a specific variant of squamous cell carcinoma [2] or that it is a lesion that may transform to squamous cell carcinoma. [3]

Metastasis of keratoacanthoma has been reported in the literature rarely. [4] Here we present a patient who developed a metastasis in the parotid gland secondary to a skin tumor which had all the diagnostic features of a keratoacanthoma.

Report of a patient

An 81-year-old woman presented herself with a nodule on the left cheek. She told that the nodule had developed only a few months previously and had grown continuously. The patient was otherwise healthy but reported on a history of breast carcinoma several years before.

Clinically, an erythematous nodule measuring 1.5 cm in diameter was seen (Fig. 1). The nodule had a keratotic plug in the center. The clinical diagnosis was keratoacanthoma and the lesion was excised with local anesthesia.

Fig. 1

Erythematous nodule with a keratotic plug in the center.

Histopathologically, there was a symmetric crateriform proliferation of moderately pleomorphic keratinocytes (Figs. 2A-I). A parakeratotic plug was present in the center of the lesion. Keratinocytes at the periphery of the proliferation displayed crowding of nuclei and only little cytoplasm. Towards the center of the proliferation, keratinocytes were large with abundant eosinophilic cytoplasm. Individual necrotic keratinocytes and some suprabasal mitotic figures were seen. An infiltrate of inflammatory cells was accompanying. The changes were diagnostic of keratoacanthoma. No signs of vascular invasion or perineural extension were seen. The lesion seemed to be excised completely on sections stained with hematoxylin and eosin, as well as in an immunohistocchemical staining with anticytokeratin antibodies (Fig. 2I).

Figs. 2A-I

Crateriform proliferation of moderately pleomorphic keratinocytes with a parakeratotic plug in the center. Keratinocytes at the periphery of the proliferation are small and crowded, whereas towards the center keratinocytes have abundant eosinophilic cytoplasm. Fig 2I: Cytokeratin staining.

One year later, the patient presented herself with an asymptomatic subcutaneous nodule in the left preauricular region which had grown within a few weeks. On palpation, the nodule was indurated, firmly attached to the surrounding tissue, and localized in the region of the left parotid gland. Histopathologically, a proliferation of moderately pleomorphic keratinocytes was seen within the partotid gland (Figs. 3A-K). A parakeratotic plug was present in the center of the proliferation. Keratinocytes at the periphery of the proliferation displayed crowding of nuclei and only little cytoplasm. Towards the center of the proliferation, keratinocytes were large with abundant eosinophilic cytoplasm. Cytomorphologic features were very similar to those seen in the keratoacanthoma excised from the ipsilateral cheek one year before.

Figs. 3A-K

Proliferation of moderately pleomorphic keratinocytes within the partotid gland. Cytomorphologic features are very similar to those seen in the keratoacanthoma excised 1 year before. Signs of regression in the form of fibrosis and a granulomatous foreign body reaction around globules of keratin are seen within the proliferation and are very similar to those seen in regressing keratoacanthoma in skin (Figs 3I-K).

Because no other squamous cell carcinoma of the head and neck region or of the larynx and pharynx could be found in the patient and because of the cytomorphologic similarities between the keratoacanthoma and the proliferation in the parotid gland, a diagnosis of metastasis of the keratoacanthoma was made.

Complete staging revealed no further regional or distant metastases. Follow-up of three years was uneventful.

Discussion

Keratoacanthoma is a unique clinicopathological condition, and its true nature is still a matter of debate. Because of the tendency to involute and even completely regress within a few months on one han and a cytopathology indistinguishable from that of a well-differentiated squamous cell carcinoma, keratoacanthoma has long been regarded to be the prototype of a pseudomalignancy. Numerous studies have been undertaken to identify features differentiating histopathologically, immunohistochemically, or by means of molecular genetics between keratoacanthoma and squamous cell carcinoma but no definite criteria have been found to date. [5-10] For those who still favor separation of the two entities, a crateriform symmetric shape of the proliferation together with a typical clinical appearance of a nodule with a keratotic plug in the center are the most important criteria for differentiation. Metastasis of keratoacanthoma has been described in the literature rarely. [4,11] Hodak and coworkers presented three patients with lesions diagnosed by them as keratoacanthomas, which were followed by metastasis to a lymph node (Figs. 4A-G). Ansai and colleagues observed a patient with similar findings. [11] Others have told of vascular invasion [12] and of perineural invasion [6] in keratoacanthomas but did not consider these signs of an unequivocally malignant nature of the condition.

Figs. 4A-G

Reproduced from: Hodak E et al. Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. Am J Dermatopathol. 1993;15(4):332-42.[4]

The patient presented here had a lesion which clinically and histopathologically was typical of keratoacanthoma. The lesion in the parotid glad developed on the same side and displayed cytopathologic features strikingly similar to those of the keratoacanthoma excised previously (Figs. 2C and 3D). The parotid gland is known to be a typical site for metastasis of squamous cell carcinoma of the skin in the head and neck region. [13,14]

Interestingly, signs of partial regression in the form of fibrosis and a granulomatous foreign body reaction around globules of keratin were identified within the proliferation in the parotid gland (Figs. 3I-K). These features are identical to those seen in regressing keratoacanthoma in the skin. To date, regression of a metastasis of keratoacanthoma has been described in the literature only once by Ansai et al. [11]

The case presented here reinforces the concept that keratoacanthoma is better interpreted as a variant of squamous cell carcinoma because it is capable of metastasis and metastasizes to the same sites as does squamous cell carcinoma of the same region. Nevertheless, the phenomenon of spontaneous regression of keratoacanthoma makes the condition unique, if not as a neoplasm then as an immunological phenomenon. Based on our morphologic observations, in the proliferation in the parotid gland it seems that the very same immunological mechanisms that account for occasional complete regression of keratoacanthoma in the skin were also active in the metastatic lesion. Regression, complete or incomplete, is not only a feature of benign neoplasms, it is observed also frank malignancies such as melanoma, basal cell carcinoma, lymphomatoid papulosis, and CD30-positive anaplastic large cell lymphoma. Studies aiming to identify the specific characteristics of regressing keratoacanthoma should focus on the immunological features of the patient bearing the neoplasm rather than on histopathological, immunohistochemical, or molecular characteristics of it.

Summary

Keratoacanthoma is a keratinocytic neoplasm which has been subject of controversy over decades. Because of its tendency to regress spontaneously without any treatment, for a long time it was considered to be a pseudomalignancy. In contrast, cytopathologic features of keratoacanthoma are identical to those of a well-differentiated squamous cell carcinoma. Metastasis of keratoacanthoma has been reported in the literature rarely. Therefore, it has been suggested that keratoacanthoma is just a specific variant of squamous cell carcinoma Here we present an 81-year-old woman who developed a metastasis in the parotid gland secondary to a skin tumor which had all the diagnostic features of a keratoacanthoma. Interestingly, signs of partial regression in the form of fibrosis and a granulomatous foreign body reaction around globules of keratin were identified within the proliferation in the parotid gland.

Jasmin Broyer, M.D., is a resident in dermatology and Almut Böer-Auer, M.D., is a dermatopathologist at the Dermatologikum Hamburg, Germany. Contact corresponding author via email: boer@dermatologikum.de .

References

1. Mandrell JC, Santa Cruz D. Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma? Semin Diagn Pathol. 2009;26(3):150-63.

2. Beham A, Regauer S, Soyer HP, Beham-Schmid C. Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma. Adv Anat Pathol. 1998;5(5):269-80.

3. Sánchez Yus E, Simón P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma: a self-healing proliferation that frequently becomes malignant. 1. Am J Dermatopathol. 2000;22(4):305-10.

4. Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. Am J Dermatopathol. 1993;15(4):332-42.

5. Mandrell JC, Santa Cruz D. Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell carcinoma? Semin Diagn Pathol. 2009;26(3):150-63.

6. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion: a report of 40 cases. 1. Australas J Dermatol. 2001;42(3):168-71.

7. Beham A, Regauer S, Soyer HP, Beham-Schmid C. Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma. 1. Adv Anat Pathol. 1998;5(5):269-80

8. Sánchez Yus E, Simón P, Requena L, Ambrojo P, de Eusebio E. Solitary keratoacanthoma: a self-healing proliferation that frequently becomes malignant. Am J Dermatopathol. 2000;22(4):305-10.

9. Cain CT, Niemann TH, Argenyi ZB. Keratoacanthoma versus squamous cell carcinoma. An immunohistochemical reappraisal of p53 protein and proliferating cell nuclear antigen expression in keratoacanthoma-like tumors. Am J Dermatopathol. 1995;17(4):324-31.

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11. Ansai S, Manabe M. Possible spontaneous regression of a metastatic lesion of keratoacanthoma-like squamous cell carcinoma in a regional lymph node. J Dermatol. 2005;32(11):899-903.

12. Calonje E, Jones EW. Intravascular spread of keratoacanthoma. An alarming but benign phenomenon. Am J Dermatopathol. 1992;14(5):414-7.

13. Ch’ng S, Maitra A, Lea R, Brasch H, Tan ST.Parotid metastasis—an independent prognostic factor for head and neck cutaneous squamous cell carcinoma. Plast Reconstr Aesthet Surg. 2006;59(12):1288-93.

14. Barzilai G, Greenberg E, Cohen-Kerem R, Doweck I. Pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg. 2005;132(6):852-6.