Dermatopathology Primary cutaneous adenoid cystic carcinoma* James A. Seab, Colonel, MC, USA, and James H. Graham, M.D. Washington, DC Primary adenoid cystic carcinoma of the skin is rare. Ten cases from the files of the Armed Forces Institute of Pathology were studied. Seven of the 10 cases recurred after initial surgery. The interval between surgery and recurrence ranged from 4 months to 20 years. In one case there was metastasis to lung and pleura. Histologically, cutaneous adenoid cystic carcinoma is indistinguishable from adenoid cystic carcinoma of the salivary gland. The diagnostic histologic features and the differentiation of adenoid cystic carcinoma from other cutaneous neoplasms are discussed. (J AM ACAD DERMATOL 1987;17:113-8.)
Adenoid cystic carcinoma is an uncommon but well-recognized neoplasm of major and minor salivary glands.' It also occurs in the lacrimal gland, respiratory tract, external auditory canal, breast, cervix, and other sites. Primary cutaneous adenoid cystic carcinoma is rare. Excluding adenoid cystic carcinoma of the external auditory canal, only 10 cases have been published in the recent English language literature.P" This report adds 10 additional cases and further defines the diagnostic histologic features, differential diagnosis, and clinical behavior of cutaneous adenoid cystic carcinoma. MATERIALS AND METHODS A computer search of the Armed Forces Institute of Pathology files for potentialcases of cutaneous adenoid cystic carcinoma was done. Ten cases were identified that met the following histologic criteria: (1) the neoplasm occurred primarily in the dermis; (2) the neoplasm consisted of basaloid cells that at least in some areas showed a cribriform pattern; (3) basophilic mucinous' stroma was present and/or there were focal areas From the Department of Dermatopathology, Armed Forces Institute of Pathology. Reprint requests to: Colonel James A. Seab, Department of Dermatopathology, Armed Forces Institute of Pathology, Washington, DC 20306. *The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
of hyalinization; and (4) true glandular lumina containing sialomucin were inconspicuous or absent. Cases of adenoid cystic carcinoma affecting the external auditory canal, the skin overlying the parotid gland, and those from the lip were excluded. Follow-up information was obtained whenever possible. Hematoxylin and eosin-stained sections of formalinfixed, paraffin-embedded tissue were examined in all cases. In selected cases the following special stains were used: periodic acid-Schiff with and without diastase digestion, colloidal iron, and aldan blue at pH 2.5 and 0.4 with and without testicular hyaluronidase and sialidase digestion. The cases were divided into cribriform, tubular, and solid types as described by Perzin et al, 6 and the borders of each tumor were searched for evidence of perineural invasion. Observations. Ten cases were identified that met the histologic criteria. The clinical data are summarized in Table I. In general the patients were middle-aged adults. The age at first surgery ranged from 38 to 90. In contrast to the cases reviewed by Cooper et aI,4 most of the patients were male. All were civilian, and the male predominance does not reflect a military patient population. The duration of clinical symptoms prior to surgery was given in four patients and ranged from 2 months to 2 years. The most common site was the skin of the chest. Seven of the tumors recurred one or more times at or near the original site. Patient 6 was noteworthy in that the tumor metastasized to the lung and pleura. The histologic features are summarized in Table Il.
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Table I. Summary of clinical data Case
5 liM 43/M 74/M 48/F
4 5 6
Chest Chest Cheek Chest Scalp Scalp
0 I I 2 0 1
3 yr 1.5 yr 20 and 2 yr 1
7 8 9
Perineum Chest Thigh Hip
1 2 0 1
6 7 8 6
yr yr rna
and 6 yr
3 yr 4.5 yr 3 rna 2 rna 13.5 yr
D/FOD D/FOD D/FOD D/WD AlFOD
2 1 7 1 1
A/WD LTFU AIFOD A/FOD A/FOD
yr mo mo mo mo
"Age at first biopsy. tTime from surgery to recurrence or metastasis. :j:Time from last surgery to last known status. §A: Alive; D: dead; FOD: clinically free of adenoid cystic carcinoma; WD: with adenoid cystic carcinoma; LTFU: lost to follow-up.
n. Summary of histologic features
3 4 5
8 9 10
Predominant histologic pattern
Solid + cribriform Cribriform + tubular Cribriform Cribriform + tubular Cribriform Cribriform + tubular Cribriform Cribriform Cribriform + tubular Tubular + cribriform
Present Present Present Present Absent Present Present Present Present Present
All lesions showed at least some areas of the cribriform pattern consisting of islands ofbasaloid cells with rather uniform round spaces giving a punched-out appearance (Fig. 1). The size of both the islands and the spaces (pseudolumina) in them was variable. In most of the neoplasms studied the pseudolumina contained material that stained light blue with hematoxylin and eosin and with colloidal iron and aldan blue at pH 2.5. Most but not all the alcian blue-positive material was removed by prior digestion with hyaluronidase. Some material within the pseudolumina also stained with alcian blue at pH 0.4. The staining reaction with periodic acid-
Schiff varied with the extent of hyalinization of the material in the pseudolumina. Nonhyalinized substance stained poorly or not at all, while hyalinized material stained intensely with periodic acid-Schiff. True glandular lumina were difficult to find in most of the study cases. They consisted of small ductlike spaces bounded by cells that were somewhat larger than most of the tumor cells and contained flocculent or granular material that was strongly periodic acid-Schiff'-positive after diastase digestion. The cribriform feature was the predominant pattern in eight of the ten patients (Fig. 1), but it was frequently admixed with areas of tubular differentiation (Fig. 2). Most lesions contained at least a few tubular structures. Large areas showing a solid pattern were seen in only one patient. The solid pattern consisted of islands of basaloid cells with no or very few pseudolumina. In all patients the tumor cells were small to medium in size with small nucleoli and inconspicuous cytoplasm (Fig. I, B). Mitoses were rare. Perineural invasion (Fig. 3) was easily identified in sections of all lesions except for Patient 5, in whom well-defined margins were present. All other patients showed infiltration into the subcutaneous tissue or to the deep surgical margin. Sections from the primary and metastatic lesions from Patient 6 showed the typical histologic features of cutaneous adenoid cystic carcinoma (Fig. 4). DISCUSSION Adenoid cystic carcinoma accounts for 5% to 15% of salivary gland tumors.' It has also been reported in numerous other sites, including lacrimal gland, respiratory tract, breast, and cervix.":'
Volume 17 Number 1 July 1987
Primary cutaneous adenoid cystic carcinoma
Fig. 1. A and B, Cutaneous adenoid cystic carcinoma showing the characteristic cribriform pattern. Tumor cells are basaloid with inconspicuous cytoplasm. (A, X 60; E, X 160.)
A small series of cases in the external auditory canal were reported." Cutaneous adenoid cystic carcinoma is otherwise very rare; only 10 cases have been reported in the recent English language Iiterature.i" Adenoid cystic carcinoma of salivary gland is slow-growing but relentless. Recurrences are common and metastases develop in about half the cases with long-term follow-up. 10,11 Of the 10 previously reported cases of cutaneous adenoid cystic carcinoma, four recurred and one with a scalp lesion had metastasis to the lungs and pleura after an l l-year course with local recurrence. 2 The patients were all adult, the youngest being 34 at the time of presentation. The most common location was the scalp, but several other sites were involved. The 10 cases in the present study were similar. The patients were adults of middle age or older who had a cutaneous tumor when first seen. The most common location of the tumor was the chest, but in two patients the tumors occurred on the scalp. No tumors occurred on the distal extremi-
ties. Surgical excision was followed by recurrence of the tumor in 7 patients. The lesion recurred locally for a second time in 2 patients. Patient 6 was similar in many ways to the patient reported in the literature who had cutaneous adenoid cystic carcinoma with metastasis." Both patients were female and had tumors of the scalp that recurred several years after the initial surgical excision. Case 5 was also of special interest. It was the only case in the present study with a long postsurgery follow-up (13.5 years) without recurrence of the tumor. It was also the only case in which perineural invasion was absent. The sections showed a comparatively small and well-circumscribed tumor. These observations suggest that patients with small, well-circumscribed tumors without perineural invasion may have the best chance of complete cure by surgical excision. The diverse locations of adenoid cystic carcinoma suggest that it is a specific histologic pattern of carcinoma rather than a tumor of a specific cell
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Fig. 2. Cutaneous adenoid cystic carcinoma with a prominent tubular pattern. In other areas the tumor showed the cribriform pattern. (X 160.)
Fig. 3. A dermal nerve surrounded and infiltrated by adenoid cystic carcinoma. (x 160.)
of origin. Electron microscopic and immunoperoxidase studies of adenoid cystic carcinoma have shown that it is an epithelial neoplasm in which the tumor cells produce basal lamina.":" This results in the characteristic and diagnostic cribriform histologic pattern. The adenoid spaces or pseudolumina first accumulate hyaluronic acid and sufated acid mucin, which appears light blue with hematoxylin and eosin and does not stain with periodic acid-Schiff. Type IV collagen has been identified within the pseudolumina by immunoperoxidase methods." Eventually the basal lamina becomes hyalinized and stains intensely with periodic acid-Schiff. The spaces are not true glands nor do they contain epithelial mucins. The epithelial cells may produce so much hyalin that they appear to become entrapped in masses of it. Extracutaneous adenoid cystic carcinoma usually shows ductular and glandular differentiation, and this feature is especially seen with electron microscopy. 12 At the light microscopy level this is characterized by inconspicuous ducts or glands
lined by cells slightly larger than the basaloid cells. The lumina may contain a secretory product that stains with periodic acid-Schiff and is removed by sialidase digestion but not by diastase digestion." These latter features do not cause confusion with the pseudolumina because the ducts are inconspicuous and do not contain hyalin. Myoepithelial cells have also been identified in extracutaneous adenoid cystic carcinoma by electron microscopy." The solid pattern of adenoid cystic carcinoma is considered the least differentiated, being composed entirely of islands of basaloid cells without pseudolumina. The tubular pattern has been considered the most differentiated one. 14 In this study islands of basaloid cells showing a cribriform pattern were considered diagnostic of cutaneous adenoid cystic carcinoma. Pure solid or pure tubular patterns could exist in theory but would be difficult to differentiate from other histologic types of sweat gland carcinoma. In some cases cutaneous adenoid cystic carci-
Volume 17 Number I July 1987
noma might be difficult to differentiate from secondary extension into the skin from an underlying tumor. IS The pathologist should consider this possibility when the biopsy specimen is from the skin over the parotid gland, or from the lip, eyelid, or ear. Metastatic adenoid cystic carcinoma to the skin is very rare"-":" and should be considered only if there is a history of a previous extracutaneous adenoid cystic carcinoma. The differential diagnosis of cutaneous adenoid cystic: carcinoma includes adenoid basal cell carcinoma, mucinous carcinoma of the skin, eccrine sweat gland carcinoma, such as malignant eccrine acrospiroma and malignant eccrine spiradenoma, metastatic adenocarcinoma, and dermal eccrine cylindroma. Adenoid basal cell carcinoma shares with cutaneous adenoid cystic carcinoma a cribriform pattern, basaloid cells, and a stroma rich in hyaluronic acid that may contain hyalin. However, the diagnosis is usually evident with a routine section. Adenoid basal cell carcinoma consists of relatively large, irregular islands with palisading borders, and the adenoid spaces contain sulfated acid mucin. Often adenoid basal cell carcinoma shows one or more connections to the epidermis, a feature that was present in only 1 of the 10 study cases. In adenoid basal cell carcinoma the stroma is more cellular and pulls away from the islands of tumor cells to form clefts. Adenoid basal cell carcinoma lacks perineural invasion except in rare examples. In rare cases in which the diagnosis cannot be made with routine sections, imrnunoperoxidase stains can be of value in distinguishing adenoid cystic carcinoma from adenoid basal cell carcinoma. Adenoid cystic carcinoma contains epithelial membrane antigen, S-l00 protein, and carcinoembryonic antigen, all of which are usually absent in adenoid basal cell carcinoma. 5 Mucinous carcinoma of the skin has been termed "adenocystic carcinoma." The term mucinous carcinoma is preferable to avoid confusion. Mucinous carcinoma of the skin consists of islands of epithelial cells that appear to float in lakes of sialomucin, which stains strongly with periodic acid-Schiff and mucicarmine. 16 Sialomucin is inconspicuous in adenoid cystic carcinoma. Cutaneous adenoid cystic carcinoma is probably closely related to, or is a type of, eccrine sweat
Primary cutaneous adenoid cystic carcinoma 117
Fig. 4. Photomicrograph of biopsy specimen from the pleura of Patient 6, showing metastatic adenoid cystic carcinoma. The tumor is histologically identical to the primary adenoid cystic carcinoma of the scalp. (X 160.)
gland carcinoma. The characteristic cribriform pattern of adenoid cystic carcinoma is the key differential feature. A hypothetical adenoid cystic carcinoma with a pure tubular pattern might be indistinguishable from some types of eccrine carcinoma. Moderately and poorly differentiated sweat gland carcinomas, such as malignant eccrine acrospiroma and malignant eccrine spiradenoma, contain larger cells with more prominent nucleoli. Metastatic carcinoma from sites such as the breast may have a cribriform pattern. The cribriform pattern of breast cancer is different from that of adenoid cystic carcinoma in that it consists of islands of cells with multiple true glandular lumina. The lumina may contain epithelial sialomucin, which stains with periodic acid-Schiff and is not removed by hyaluronidase. Hyalin is absent in metastatic breast carcinoma and often the cells are larger and more variable than the basaloid epithelium of adenoid cystic carcinoma. Adenoid cystic carcinoma has been referred to
Journal of the American Academy of Dermatology
118 Seab and Graham
as cylindroma, which might lead to confusion with dermal eccrine cylindroma. Dermal eccrine cylindroma and eccrine spiradenoma are composed of cells that are similar to those of adenoid cystic carcinoma, but both neoplasms lack the cribriform pattern and they do not show perineural invasion. Cutaneous adenoid cystic carcinoma is histologically indistinguishable from adenoid cystic carcinoma of the salivary gland and other sites. The clinical behavior of cutaneous adenoid cystic carcinoma is similar to that of adenoid cystic carcinoma of other sites in that cutaneous adenoid cystic carcinoma frequently recurs and that recurrent tumor may appear years after surgery. The rate of metastasis of cutaneous adenoid cystic carcinoma (2 of 20 cases) is lower than that of reported cases of extracutaneous adenoid cystic carcinema,":" but the number of cases is too small and the follow-up times too short to determine whether this is because of a difference in the biologic behavior of the tumors or because of the greater accessibility of cutaneous adenoid cystic carcinoma to surgical excision.
Since the completion of the study two additional cases of cutaneous adenoid cystic carcinoma were found in the Armed Forces Institute of Pathology files. One case was an 89-year-old man with a lesion of the back. The second was a 59-ye~-0Id woman with a lesion of the scalp. The second lesion recurred 4 months after excision.
Armed Forces Institute of Pathology, 1974;91-9. (Second series, fascicle 10.) Sanderson KV, Batten JC, Adenoid cystic carcinoma of the scalp. Proc R Soc Med (Lond) 1975;68:649-50. Headington JT, Teears R, Niederhuber lE, Slinger RP. Primary adenoid; cystic carcinoma of the skin. Arch Dermatol 1978;114:421-4. Cooper PH, Adelson GL, Holthaus WH. Primary cutaneous adenoid cystic carcinoma. Arch Dermatol 1984; 120:774-7. Wick MR, Swanson PE. Primary adenoid cystic carcinoma of the skin. Am J Derrnatopathol 1986;8:2-13. Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinomas arising in salivary glands, Cancer 1978; 42:265-82. Zaloudek C, Oertel YC, Orenstein JC. Adenoid cystic carcinoma of the breast. Am J Clin Pathol1984;81:297307. Mazur MT, Battifora HA. Adenoid cystic carcinoma of the uterine cervix: ultrastructure, immunofluorescence, and criteria for diagnosis. Am J Clin Pathol1982;77:494500. Perzin KD, Gullane P, Conley J. Adenoid cystic carcinoma involving the external auditory canal. Cancer 1982;50:2873-83. Nascimento AG, Amaral LP, Prado LAP, Kligerman J, Silveira TRP. Adenoid cystic carcinoma of salivary glands. Cancer 1986;57:312-9. Matsuba HM, Spector GJ, Thawley SE, Simpson JR, Mauney M, Pikul FJ. Adenoid cystic salivary gland carcinoma. Cancer 1986;57:519-24. Chauydhry .AP, Leifer C, Cutler LS, Satchidanand S, Labay GR, Yamane GM;. Histogenesis of adenoid cystic carcinoma of the salivary glands. Cancer 1986;58:72-82. Azzopardi JG, Smith Ol). Salivary gland tumours and their mucins. J Pathol Bactiol 1959;77:131-40. Szanto PA, Luna MA, Tortoledo E, White RA. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 1984;54:1062-9. King DT, Cihak RW, Luther PK, Gurevitch AW, Hirose PM. Malignant neoplasms of the paranasal sinuses involving the skin. Arch Dermatol 1978;114:1681-3. Mendoza S, Helwig EB. Mucinous (adenocystic) carcinoma of the skin. Arch Dermatol 1971;103:68-78.
1. Thackray AC, Lucas RI\. Tumors of the major salivary glands. In: Atlas of tumor pathology. Washington DC:
ABSTRACTS Granuloma faciale: treatment with cryotherapy
Broader spectrum of tick-borne spirochetoses
Verdeguer Miralles JM, Jorda Cuevas E, Ramon Quiles D, Barreda Miralles C. Aetas Derrno-Sif 1986;77:515-8 (Spanish)
Rufli T, Lehner S, Aeschlimann A, Chamot E, Gigon F, Jaenneret J-P. Hautarzt 1986;37:597-602 (German)
A 33-year-old man with biopsy-proved granuloma faciale of the right cheek of 1 year's duration failed to respond to dapsone, 100 mg daily for a month, and chloroquine, 250 mg daily for a month. Liquid nitrogen cryotherapy, using a cotton-tipped applicator, was successful in completely eradicating the lesions, with little residual scarring and no recurrence. Yehudi M. Felman. M.D.
On the basis of case histories and serologic investigation, the authors suggestthat some cases of localizedscleroderma and macular anetoderma may be caused by a tickborne spirochete. Microbiologic confirmation of this suggestion is, so far, lacking. Yehudi M. Felman, M.D.