Cases of Interest: Not Everything Meets the Eye

by Bruce D. Ragsdale, MD
Western Dermatopathology 

An otherwise healthy 33-year-old woman gave a 6-week history of a left superolateral orbital mild tenderness, ptosis, proptosis, and diplopia on upgaze. MRI shows a superolateral orbital mass (Figs. 1 & 2). A biopsy was performed (Fig. 3).

This is:

  • Spiradenoma
  • Spiradenocarcinoma
  • Spiradenocylindrocarcinoma
  • Adenoid cystic carcinoma of the lacrimal gland
  • Eccrine carcinoma
  • Glandular schwannoma
  • Metastatic carcinoma

Diagnosis: Adenoid cystic carcinoma of the lacrimal gland with spiradenoma-like areas

An adnexal skin tumor occurring near a salivary gland may resemble and be confused with a gland neoplasm, especially of parotid (14), and as illustrated here, an adenoid cystic carcinoma (ACC) of the lacrimal gland.

Solid nests of unequivocal malignancy (lower right, Fig. 4) are bordered by a pattern closely resembling benign eccrine spiradenoma (upper left, Fig. 4 and Fig. 3). This tumor would fit skin adnexal origin if it was arising on the eyebrow or near the eyelid and then grew into the orbit. Thus, the initial consideration (because our first love is dermpath) was that of a malignant spiradenoma (spiradenocarcinoma) arising in an eccrine spiradenoma. It is said that recognition of three cell types in eccrine spiradenomas, including epithelial cells, myoepithelial cells and lymphocytes, as compared to the single cell type in ACC, is paramount in avoiding this potential pitfall in diagnosis (14). But the "spiradenoma nests" in the present specimen with their PAS-positive basement membrane droplets (lower right in Fig. 5) had all three cell types: keratin-positive epithelial cells, actin-positive myoepithelial cells, and CD45-positive lymphocytes. In true eccrine spiradenoma, co-expression of cytokeratin and smooth muscle actin suggests differentiation toward myoepithelial cells (15) and was present here, enhancing the mimicry of spiradenoma.

Eccrine spiradenoma is a benign skin adnexal neoplasm that usually appears as a solitary nodule, potentially in any skin area. Malignant change arising within one is rare (10). The diagnosis hinges on finding a benign component (2), which was initially thought present here.

Spiradenoma/cylindroma with admixed carcinoma is referred to in the literature as carcinoma ex spiradenoma/cylindroma and spiradenocylindrocarcinoma (12, 13). Most cases originate in a longstanding cutaneous lesion and can occur in the setting of Brooke-Spiegler syndrome (13). As of 2001, there were only 33 reports on malignant transformation of a benign eccrine spiradenoma since the first description by Dabska in 1972 (5); by 2005 there were just 48 in the English literature (3). The term "spiradenocylindrocarcinoma" is proposed to describe malignant tumors with features of both a spiradenoma and a cylindroma (3). It is a neoplasm that displays a range of microscopic appearances (21). Malignancy is evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, and hyperchromasia, loss of nested and trabecular growth patterns, and absence of a dual cell population (7), epithelial and myoepithelial.

An ACC-like pattern in spiradenoma and spiradenocylindroma is a distinctive finding in a minority of cases and extends the morphological spectrum of the two, occurring sporadically or in the setting of Brooke-Spiegler syndrome (18). The ACC-like areas are typified by cribriform formations of epithelial cells concentrically arranged around gland-like spaces filled with mucin (not unlike Fig. 6), homogeneous eosinophilic material, or granular basophilic material (18).

But a literature review in 2001 found only four cases of solitary spiradenoma of the eyelid (8) and I could find none that extended into the orbit. This motivated a call to the clinician for additional context. The clinician averred this was an orbital tumor in contact with the lacrimal gland and did not involve brow skin. This spurred further review of the slides and the conclusion that the cribriform pattern with mucicarmine-positive mucin in the spaces, inclusions of benign lacrimal gland in the tumor (Fig. 7), and perineural involvement fit adenoid cystic carcinoma with a basaloid (solid) component. The three cell type composition—epithelial, myoepithelial, and lymphocytes—was absent in the adjacent cribriform ACC nest (e.g., upper left in Fig. 5). A further clue pointed away from spiradenoma: Abundant Langerhans cells are said present within lobules of a spiradenoma (1) but were absent in this tumor, according to an S100 reaction. So the diagnosis of ACC was rendered, despite the inability to find a report of spiradenoma features in a lacrimal gland tumor. Of note, though, one reference work states: "Cutaneous glands include the sebaceous, sweat, lacrimal, and mammary glands". Mixed tumors occur in lacrimal glands, salivary glands, and eccrine glands (chondroid syringoma). This may well be a first case of spiradenoma-like features in adenoid cystic carcinoma of lacrimal gland.

Among primary lacrimal gland tumors, adenoid cystic carcinoma is the most common malignant epithelial neoplasm (19) and arises from precursor cells of the terminal duct system (9). The cribriform pattern of ACC was juxtaposed to a monomorphous and mitotically active small epithelial cell population, a basaloid (solid) component (Fig. 4) which is an adverse prognostic feature (6). Larger nests of the monomorphous, expansile basaloid component showed central comedonecrosis in keeping with malignancy. Treatment for ACC of the lacrimal gland varies from globe-preserving surgery to orbital exenteration with bone removal, with or without radiotherapy after the surgical option chosen. Tumor extended to the deep biopsy plane. Some tumor persisted after a complete resection attempt three weeks later.

A 2004 M. D. Anderson Cancer Center report of 20 cases of lacrimal gland ACC followed for a mean time of 34 months records distant metastases in 80%. Delayed hematogenous metastases are seen. At the time of the report, 13 (65%) of the patients had died of disease. The median disease-free survival for the entire group was 18 months. This study underscores the generally grave prognosis for patients with ACC of the lacrimal gland and the difficulty in making any conclusive recommendations for local therapy of this disease.

Since it is a very recent case, long-term follow-up is not presently available on our patient.

References

  1. al-Nafussi A, Blessing K, Rahilly M. Non-epithelial cellular components in eccrine spiradenoma: a histological and immunohistochemical study of 20 cases. Histopathology. 1991 Feb;18(2):155-60.
  2. Biernat W, Wozniak L. Spiradenocarcinoma: a clinicopathologic and immunohistochemical study of three cases. Am J Dermatopathol. 1994 Aug;16(4):377-82.
  3. Carlsten JR, et al. Spiradenocylindrocarcinoma: a malignant hybrid tumor. J Cutan Pathol. 2005 Feb;32(2):166-71. Erratum in: J Cutan Pathol. 2005 Jul;32(6):453.
  4. Eckert F, et al. Myoepithelial differentiation in benign sweat gland tumors. Demonstrated by a monoclonal antibody to alpha-smooth muscle actin. J Cutan Pathol. 1992 Aug;19(4):294-301.
  5. Fernández-Aceñero MJ, Manzarbeitia F, Mestre de Juan MJ, Requena L. Malignant spiradenoma: report of two cases and literature review. J Am Acad Dermatol. 2001 Feb;44(2 Suppl):395-8.
  6. Gamel JW, Font RL. Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern. Hum Pathol. 1982 Mar;13(3):219-25.
  7. Granter SR, Seeger K, Calonje E, Busam K, McKee PH. Malignant eccrine spiradenoma (spiradenocarcinoma): a clinicopathologic study of 12 cases. Am J Dermatopathol. 2000 Apr;22(2):97-103.
  8. Gupta S, Radotra BD, Kaur I, Handa S, Kumar B. Multiple linear eccrine spiradenomas with eyelid involvement. J Eur Acad Dermatol Venereol. 2001 Mar;15(2):163-6.
  9. Holz FG, et al. [Adenoid cystic carcinoma of the lacrimal gland]. Klin Monbl Augenheilkd. 1992 Jul;201(1):42-7. German.
  10. Ishikawa M, Nakanishi Y, Yamazaki N, Yamamoto A. Malignant eccrine spiradenoma: a case report and review of the literature. Dermatol Surg. 2001 Jan;27(1):67-70.
  11. Jin Y, et al. Characteristic karyotypic features in lacrimal and salivary gland carcinomas. Br J Cancer. 1994 Jul;70(1):42-7.
  12. Jukic DM, et al. Carcinoma ex spiradenoma/cylindroma confirmed by immunohisto-chemical and molecular loss-of-heterozygosity profiling. Am J Dermatopathol. 2009 Oct;31(7):702-8.
  13. Kazakov DV, et al. Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome. Am J Surg Pathol. 2009 May;33(5):705-19.
  14. Kolda TF, et al. Eccrine spiradenoma mimicking adenoid cystic carcinoma on fine needle aspiration. A case report. Acta Cytol. 1997 May-Jun;41(3):852-8.
  15. Kurokawa I, et al. Eccrine spiradenoma: co-expression of cytokeratin and smooth muscle actin suggesting differentiation toward myoepithelial cells. J Eur Acad Dermatol Venereol. 2007 Jan;21(1):121-3.
  16. Lee DA, et al. A clinicopathologic study of primary adenoid cystic carcinoma of the lacrimal gland. Ophthalmology. 1985 Jan;92(1):128-34.
  17. Penner CR, et al. C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Mod Pathol. 2002 Jul;15(7):687-91.
  18. Petersson F, et al. Adenoid cystic carcinoma-like pattern in spiradenoma and spiradenocylindroma: a rare feature in sporadic neoplasms and those associated with Brooke-Spiegler syndrome. Am J Dermatopathol. 2009 Oct;31(7):642-8.
  19. Terasaki M, et al. High-grade adenoid cystic carcinoma originating from the lacrimal gland. Brain Tumor Pathol. 2000;17(3):159-63.
  20. You JQ, Wang P. [Protein expression of p53, bcl-2, and bax in adenoid cystic carcinoma of lacrimal gland]. Zhonghua Yi Xue Za Zhi. 2008 Jul 22;88(28):1978-82. Chinese.
  21. Wick MR, et al. Sweat gland carcinoma ex eccrine spiradenoma. Am J Dermatopathol. 1987 Apr;9(2):90-8.
  22. Esmaeli B, et al. Outcomes in patients with adenoid cystic carcinoma of the lacrimal gland. Ophthal Plast Reconstr Surg. 2004 Jan;20(1):22-6.