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Year : 2013  |  Volume : 58  |  Issue : 4  |  Page : 326
Cutaneous syringoma: A clinicopathologic study of 34 new cases and review of the literature

Department of Dermatopathology, Autoimmune Bullous Diseases Research Center, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication25-Jun-2013

Correspondence Address:
Alireza Ghanadan
Department of Dermatopathology, Autoimmune Bullous Diseases Research Center, Razi Hospital, Tehran University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.113956

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Background: Syringoma is a benign adnexal tumor derived from intraepidermal eccrine duct. Aim: The aim of the study is to report the experience concerning syringoma by reviewing the clinical and histopathologic features of a series of 34 histologically diagnosed syringoma patients observed over a period of six years. Materials and Methods: Thirty-four patients were sorted into two groups, localized and generalized syringoma, according to the Friedman and Butler classification. Different histopathologic findings were recorded in specially designed questionnaires for further analysis. Results: Ninety-seven percent of the patients were females with the mean age of 27.6 years. The mean duration of the lesions before the presentations was six years. The diagnosis of syringoma was only considered in 23 patients (67.6%) and was the initial diagnosis in only 13 (38.2%) patients. All histological findings were seen more common in our cases. in comparison to the documented cases in the literature. Clear cell change of epithelial eccrine cells was 85.2% and there was no difference in the histopathological findings in the two groups. Our patients with generalized syringoma (GS) had a considerable lower age of onset than the ones with localized syringoma (LS) ( P = 0.027). Conclusion: Our patients with generalized syringoma were younger than the ones with localized syringoma. Distribution of the generalized syringoma was mainly in the chest and neck followed by the forearms whereas localized syringoma was mostly confined to the face, axilla and genitalia. There were also some conditions associated with our cases including sarcoidosis, calcinosis cutis and basal cell carcinoma.

Keywords: Eruptive, histopathology, immunohistochemistry, syringoma

How to cite this article:
Ghanadan A, Khosravi M. Cutaneous syringoma: A clinicopathologic study of 34 new cases and review of the literature. Indian J Dermatol 2013;58:326

How to cite this URL:
Ghanadan A, Khosravi M. Cutaneous syringoma: A clinicopathologic study of 34 new cases and review of the literature. Indian J Dermatol [serial online] 2013 [cited 2023 Jun 4];58:326. Available from:

What was known?
1. Syringoma is a benign adnexal tumor derived from intraepidermal eccrine. 2. Syringoma is more prevalent in young women.

   Introduction Top

Syringoma is a benign adnexal tumor derived from intraepidermal eccrine ducts which occur predominantly in women in early adulthood. Clinically, they appear as multiple, small, firm, skin-colored or slightly yellow soft papules, 1-3 mm in diameter, symmetrically distributed and usually asymptomatic. [1],[2],[3],[4] Eruptive syringoma is a rare variant that typically develops on the face, anterior surfaces of the neck, chest, abdomen, upper extremities and genitalia. Most studies emphasize that the diagnosis of syringoma, particularly eruptive syringoma, usually was not suspected clinically and the definitive diagnosis is made by histological examination.

Although the most frequent type of the disease is the involvement of eyelids in middle-aged women, many other clinical variants have been reported. [1] Here we introduce 34 new cases of syringoma, with different ages of onset, locations and clinical manifestations with specific associated conditions, classified into localized and generalized syringoma on the basis of the classification criteria proposed by Friedman and Butler; Which is a classification of syringoma based on the clinical features consisting of four variants as follow: Localized form, a familial form, a form associated with Down's syndrome and a generalized form. [1]

   Materials and Methods Top

We reviewed our database to find the patients who presented with cutaneous syringoma and were referred to our clinic in the Department of Pathology, Razi Hospital, Tehran University of Medical Sciences. The data were obtained from our medical records during March 2005 to March 2011 and all patients' pathology samples were reexamined in order to confirm the diagnosis. Thirty-four cases of syringoma were selected for this retrospective study. We arranged our patients into two groups based on the classification criteria proposed by Friedman and Butler, localized syringoma which is confined to a solitary site as group 1 and generalized syringoma with more than one site involvement as group 2. The sections, stained with hematoxylin and eosin, were reviewed by two dermatopathologists and different histopathologic findings were recorded in specially designed questionnaires. Further descriptive analysis was performed using SPSS software Version 19. A P value of < 0.05 was considered to be statistically significant.

   Results Top

Epidemiological, clinical and histopathological features of the patients diagnosed with syringomas are summarized in [Table 1], [Table 2], [Table 3], [Table 4].
Table 1: Clinical and associated conditions in 34 cases of syringoma

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Table 2: Clinical characteristic of 34 cases of syringoma

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Table 3: Most common clinical differential diagnosis of 34 patients of syringoma

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Table 4: Histopathologic characteristics of 34 cases of syringoma

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Demographic and clinical description

Thirty-four patients, consisting of 33 females (97%) and 1 male (3%), (female/male ratio = 33/1) were included into the study. The mean age of the patients at onset of the disease was 27.6 years (range 5-63 years). Thirteen patients (38.2%) were under 20 and all our patients except one were postpubertal. The onset age of 12 patients was in the 3 rd decade, 8 patients in the 2 nd , and 9 patients in the 4 th while in the other patients the age of onset was equally distributed among the 1 st , 5 th , 6 th and 7 th decades [Graph 1[Additional file 1]]. Overall, our patients with generalized syringoma had a considerably lower age of onset than those with localized syringoma (P = 0.027) [Graph 2[Additional file 2]].

The duration of the lesions before presentations varied from 1 month to 27 years (mean 6 years). Eruptive syringoma included 6 and 11 cases in the localized and generalized group, respectively. None of our patients had familial history of syringoma. All the patients were healthy and no clinical complication was detected. No patient mentioned subjective symptoms except two patients with the complaint of pruritus. The most frequent lesions were asymptomatic multiple flesh-colored to yellowish or slightly hyperpigmented papules 3-5 mm in size [Figure 1], [Figure 2], [Figure 3], [Figure 4]. The most frequent sites were the face (periorbital), chest, abdomen, neck, forearm, hands, arm, thigh, axillae and labia minor [Table 2]. All lesions in LS were multiple and the face was the most frequent site of involvement whereas chest, neck and forearm were the most common sites of involvement in GS. The face syringomas were mostly confined to the periorbital areas but in three cases the forehead, cheeks and perioral areas were also involved. A seven-month pregnant woman had presented with papules and nodules of labia minor since fourth months of pregnancy. Calcinosis cutis was associated with syringoma of both hands in a 22-year-old woman. The only and unique male patient with syringoma of the face had presented with papules on the trunk from 27 years ago which were histologically suggestive of sarcoidosis.
Figure 1: Flesh - colored papules on the neck (Patient 29)

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Figure 2: Flesh - colored papules on the neck (Patient 20)

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Figure 3: Cutaneous syringoma in forearm (Patient 21)

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Figure 4: Cutaneous syringoma on forehead (Patient 15)

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Clinical differential diagnosis

Syringoma was considered in 23 patients (67.6%) and was the first clinical impression in only 13 patients. Other differential impressions in the order of frequency were xanthoma (15 cases), flat wart (13 cases), sarcoidosis (11 cases), lichen planus (9 cases), granuloma annulare (4 cases), adnexal tumor (4 cases) and histiocytosis (4 cases). In 11 cases, syringoma was not suspected clinically and the diagnosis was made by histological examination [Table 3]. Clinical impression of syringoma was considered only in 11 and 12 patients of GS and LS, respectively. Xanthoma is more impressive in clinic of LS, whereas, wart, granuloma annulare and histiocytosis are more frequent in the clinical impression of GS.

Histopathologic findings

Histopathologic examination of all our cases was reviewed by two dermatopathologists and the diagnosis was confirmed histologically. No histopathologic difference was seen between LS and GS. All histologic features reported in the literature including nests of eccrine ducts and tadpole-like structures embedded in fibrous stroma and clear cell changes of epithelial cells were present in our cases with a variable ratio [Figure 5] and [Figure 6]. Also, some additional findings, not previously reported in the literature, presented in our cases as acanthosis, hyperpigmentation of basal keratinocytes, keratin cyst/milia-like structures and telangectasia of superficial vessels [Table 4]. A 22-year-old girl with bilateral generalized syringoma since four years revealed calcinosis cutis on the hand [Figure 7]. On the whole all different histological characteristics were more frequent in our cases in comparison to the documented cases in the literature. Clear cell change of epithelial eccrine cells was 85.2% (more than reported in the literature). Finally, we did not notice any correlation between clinical presentation and histopathology findings.
Figure 5: Eccrine comma - shaped and tadpole strands embedded in fibrous stroma (H and E, ×10)

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Figure 6: Eccrine gland with clear cell change (H and E, ×40)

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Figure 7: Calcinosis cutis in dermis (H and E, ×10) (Patient 33)

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   Discussion Top

Syringomas are benign adnexal tumors that derive from acrosyringium, the intraepidermal portion of eccrine sweat ducts. [1],[2],[3],[4] Recently, lower acrosyringium origin or the transitional portion between the acrosyringium and dermal duct have been also suggested as origins. [5],[6] Syringoma typically appears around puberty and the women are most commonly affected. Although the localized variant of syringoma in eyelids of middle-aged women is the most frequent type, many other clinical variants have been reported up to now. [1]

Clinical findings

Eruptive syringoma is a rare variant, which typically occurs in the generalized form with the same distribution. [2],[3],[4] In a study by Patrizi et al., 19 cases of 29 cases were eruptive which is more frequent in comparison to our series (19 from 34 cases). [1] Occasionally, however, generalized eruptive syringoma develops in a more widespread distribution. [7] Other rare clinical forms include unilateral linear, [8] lichen planus-like, alopecia, [9] or milium-like syringoma. [10]

Syringoma occurs more frequently in women (75-90%). [4] In the current series 97% of patients were female; this may be attributed to the more frequent medical care seeking due to cosmetic reasons in women. [11] In the study by Patrizi et al., in the Italian population, [1] male patients were more frequent (13 men from 29 cases) in comparison to the other studies (8 men from 61 cases in a study in the Korean population by Lee et al.,[11] and 3 men from 27 cases in a study in the Spanish population by Soler-Carrillo et al.[4] both similar to our study.)

Syringoma may be familial [11],[12],[13] 11.5% of patients had positive family history of syringoma in the study by Lee et al.[12] Familial and unilateral syringoma results from mutations either within the zygote or from later postzygotic somatic mutations, which may or may not affect gonadal mosaicism in the affected patients. [12] Actually there was no positive familial history in our series.

The most frequent site of syringoma is eyelids. [1] However, in eruptive syringoma, the most frequent sites include the anterior trunk, neck, axillae, shoulders, abdomen and pubic area. There are some differences between prepubertal and postpubertal localizations. The neck and anterior trunk are the most frequent sites before the age of 15 followed by apocrine localizations. After 15 years of age, the apocrine localization is infrequent. [4] All our patients except one were postpubertal and the distribution of the generalized lesions was compatible with the previously mentioned studies, in which the most frequent sites were the chest, abdomen and neck followed by forearms. [4] The prepubertal patient had generalized eruptive syringoma with multiple location involvement.

Patrizi et al.,[1] described cases with an exclusive involvement of the wrists and forearms and suggested a variant of acral syringoma. In our series, nine cases with acral syringoma were identified but five cases were associated with involvements of other sites. Atypical sites of involvement include scalp, penis, buttock, and moustache area. [15],[16],[17] Vulvar syringoma has been commonly described in association with extragenital lesions. [18] However, in our study, only in one case, localized syringoma was limited to the genitalia (labia minor) without any extragenital involvement.

Our patients with generalized syringoma were significantly younger than those with localized syringoma (P = 0.027). The widespread distribution of the lesions through the body in the generalized form could be a reason for earlier consultation of a physician.

In the study by Soler-Carrillo et al., [4] the mean delay in consulting had been six years from the onset of the disease, similar to our study and the duration of generalized syringoma was less than localized ones [Table 2]. The diagnosis of syringoma was only considered in 23 patients and was the initial diagnosis in only 13 patients (11 and 8 of 27 cases respectively in the study by Soler-Carrillo et al., with the case number close to ours). [4] In another study, the concordance rate of syringoma diagnosis was 68.9% and other differential diagnoses were verruca plana, bowenoid papulosis, keratosis pilaris, sarcoidosis, xanthelasma, and sebaceous hyperplasia. [15] Other studies also noted that the clinical diagnosis of syringoma, particularly the eruptive variant, was usually not suspected. [12]

Clinically, eruptive syringoma may be mistaken for acne vulgaris, sebaceous hyperplasia, milia, lichen planus, eruptive xanthoma, urticarial pigmentosa, or hidrocystoma. [19] In our study, the most frequent clinical differential diagnosis of localized syringoma was xanthoma. This could be due to the similar localization of periocular syringoma with xanthelasma. Plane warts were the most common clinical differential diagnosis of generalized syringoma. Milia were the initial clinical impression in only one of our cases. Granuloma annulare and histiocytosis were in the differential diagnosis of generalized syringoma but not in localized syringoma [Table 3]. Calcinosis cutis associated with syringoma has been reported in a patient with Down's syndrome, developing on the dorsal surface of the hands and the face. [20] In our series, a 22-year-old lady with symmetrical syringoma was associated with calcinosis cutis in both hands (Case 33).

Histopathologic findings

The definite diagnosis of syringoma can be made on histopathological examination. Haematoxylin-eosin stain shows the presence of multiple small ducts and epithelial cords within the dermis. The ducts are lined by two rows of flattened epithelial cells, the outer layer bulging outwards to create a comma-like tail. Ductal lumina are filled with an amorphous, periodic acid-Schiff-positive material. [4],[19] Histologically, syringomas react strongly with S-100, the carcinoembryonic antigen, epithelial membrane antigen, lysozymes, and antibodies to the breast cystic fluid protein GCDFP-15 and GCDFP-24. In addition eccrine gland enzymes, such as succinic dehydrogenase, phosphorylase, and leucine aminopeptidase predominate in syringoma cells. [21],[22],[23]

Lee et al., found fibrosis and basal cell hyperpigmentation more frequently in erythematous and brown-colored lesions respectively. They found keratin cysts less frequently in genital syringoma. [12] In our patients keratin cysts were present only in generalized lesions. Most of the histologic criteria were more frequent in the present study than the previous ones [Table 4]. Syringomas were reported in association with other lesions such as interadermal nevus, basal cell carcinoma (BCC), carcinoid tumor and epidermal cyst. [24],[25],[26],[27] In our study one case of periorbital solitary syringoma was associated with BCC of the nose.

Clear cell syringoma is a rare variant of syringoma which is clinically indistinguishable from common variants. This variant is strongly associated with diabetes mellitus. [12],[17],[22],[28] It results from glycogen deposits in syringoma as a result of phosphorylase deficiency which occurs in diabetic patients. [17] Clear cell variant was present in only one of the 29 cases of syringoma in the Patrizi et al., series of syringoma patients and this patient was not diabetic. [1] However, in our study 29 of 34 syringoma patients showed clear cell changes and none of them were diabetic. There was no difference in the frequency of clear cell changes between localized and generalized syringomas.

   References Top

1.Patrizi A, Neri I, Marzaduri S, Varotti E, Passarini B. Syringoma: A review of twenty-nine cases. Acta Derm Venereol 1998;78:460-2.  Back to cited text no. 1
2.Pruzan DL, Esterly NB, Prose NS. Eruptive syringoma. Arch Dermatol 1989;125:1119-20.  Back to cited text no. 2
3.Hashimoto K, Blum D, Fukaya T, Eto H. Familial syringoma. Case history and application of monoclonal anti-eccrine gland antibodies. Arch Dermatol 1985;121:756-60.  Back to cited text no. 3
4.Soler-Carrillo J, Estrach T, Mascaró JM. Eruptive syringoma: 27 new cases and review of the literature. J Eur Acad Dermatol Venereol 2001;15:242-6.  Back to cited text no. 4
5.Eckert F, Nilles M, Schmid U, Altmannsberger M. Distribution of cytokeratin polypeptides in syringomas. An immunohistochemical study on paraffin-embedded material. Am J Dermatopathol 1992;14:115-21.  Back to cited text no. 5
6.Ohnishi T, Watanabe S. Immunohistochemical analysis of keratin expression in clear cell syringoma. A comparative study with conventional syringoma. J Cutan Pathol 1997;24:370-6.  Back to cited text no. 6
7.Jamalipour M, Heidarpour M, Rajabi P. Generalized eruptive syringomas. Indian J Dermatol 2009;54:65-7.  Back to cited text no. 7
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10.Wang KH, Chu JS, Lin YH, Hu CH, Lee WR. Milium-like syringoma: A case study on histogenesis. J Cutan Pathol 2004;31:336-40.  Back to cited text no. 10
11.Saha A, Das NK, Gharami RC, Chowdhury SN, Datta PK. A clinico-histopathological study of appendageal skin tumors, affecting head and neck region in patients attending the dermatology OPD of a tertiary care centre in Eastern India. Indian J Dermatol 2011;56:33-6.  Back to cited text no. 11
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12.Lee JH, Chang JY, Lee KH. Syringoma: A clinicopathologic and immunohistologic study and results of treatment. Yonsei Med J 2007;48:35-40.  Back to cited text no. 12
13.Draznin M. Hereditary syringomas: A case report. Dermatol Online J 2004;10:19.  Back to cited text no. 13
14.Smith KJ, Skelton HG. Familial syringomas: An example of gonadal mosaicism. Cutis 2001;68:293-5.  Back to cited text no. 14
15.Lo JS, Dijkstra JW, Bergfeld WF. Syringomas on the penis. Int J Dermatol 1990;29:309-10.  Back to cited text no. 15
16.Paquette DL, Massa MC. An unusual presentation of syringomas on the buttocks. J Am Acad Dermatol 1998;39:1032-3.  Back to cited text no. 16
17.Nguyen DB, Patterson JW, Wilson BB. Syringoma of the moustache area. J Am Acad Dermatol 2003;49:337-9.  Back to cited text no. 17
18.Miranda JJ, Shahabi S, Salih S, Bahtiyar OM. Vulvar syringoma, report of a case and review of the literature. Yale J Biol Med 2002;75:207-10.  Back to cited text no. 18
19.Teixeira M, Ferreira M, Machado S, Alves R, Selores M. Eruptive syringomas. Dermatol Online J 2005;11:34.  Back to cited text no. 19
20.Maroon M, Tyler W, Marks VJ. Calcinosis cutis associated with syringomas: A transepidermal elimination disorder in a patient with Down syndrome. J Am Acad Dermatol 1990;23:372-5.  Back to cited text no. 20
21.Marrogi AJ, Wick MR, Dehner LP. Benign cutaneous adnexal tumors in childhood and young adults, excluding pilomatrixoma: Review of 28 cases and literature. J Cutan Pathol 1991;18:20-7.  Back to cited text no. 21
22.Goyal S, Martins CR. Multiple syringomas on the abdomen, thighs, and groin. Cutis 2000;66:259-62.  Back to cited text no. 22
23.Sadahira C, Yoneda K, Kubota Y. Elevated levels of serum carcinoembryonic antigen in a patient with eruptive syringoma. J Am Acad Dermatol 2005;53:532-3.  Back to cited text no. 23
24.Malhotra R, Bhawan J, Stadecker M. Association of syringoma and intradermal nevus. Int J Dermatol 1986;25:397.  Back to cited text no. 24 Sousa Fernandes B, Caviggioli F, Di Tommaso L. Basal cell carcinoma adjacent to syringoma in periorbital skin: A case report. Am J Dermatopathol 2005;27:362-3.  Back to cited text no. 25
26.Berbis P, Fabre JF, Jancovici E, Privat Y, Benderitter T. Late-onset syringomas of the upper extremities associated with a carcinoid tumor. Arch Dermatol 1989;125:848-9.  Back to cited text no. 26
27.Zhu WY. Vulvar syringoma associated with epidermal cyst. Int J Dermatol 1989;28:142-3.  Back to cited text no. 27
28.Timpanidis PC, Lakhani SR, Groves RW. Progesterone receptor-positive eruptive syringoma associated with diabetes. J Am Acad Dermatol 2003;48 Suppl 5:S103-4.  Back to cited text no. 28

What is new?
1. Patients with generalized syringoma were significantly younger than the localized ones. 2. Duration of persisting syringoma for generalized types was less than localized ones. 3. Clear cell change in syringoma is more common than previously identified.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2], [Table 3], [Table 4]

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