Document Detail

Papillary adenocarcinoma in situ of the skin: report of four cases.
Jump to Full Text
MedLine Citation:
PMID:  24855569     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Although rare isolated cases of adenocarcinoma in situ of skin have been reported in the literature, adenocarcinoma in situ of skin as a concept and as a diagnostic category has not been established in the field of dermatopathology. In this work, four cases of papillary adenocarcinoma in situ of the skin are presented. In addition, the notion that lesions previously reported in the medical literature under the term of "papillary eccrine adenoma" are actually adenocarcinoma in situ is discussed.
Sheng Chen; Masoud Asgari
Related Documents :
21756019 - Idiopathic pontine streptococcus salivarius abscess in an immunocompetent patient: mana...
12183429 - Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusi...
23133769 - Lymphoepithelioma-like carcinoma of the skin treated with wide local excision and chemo...
24179659 - Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical path...
24911939 - Compartment syndrome because of acute hemorrhagic edema of infancy: a case report and l...
2682549 - Meta-analysis: whither narrative review?
16759329 - Parry-romberg syndrome: a report of the dental findings in a child followed up for 9 ye...
24575719 - Bmc urology reviewer acknowledgement, 2013.
11987109 - Separation of xiphi-omphalo-ischiopagus tetrapus twins with favorable internal anatomy.
Publication Detail:
Type:  Journal Article     Date:  2014-04-30
Journal Detail:
Title:  Dermatology practical & conceptual     Volume:  4     ISSN:  2160-9381     ISO Abbreviation:  Dermatol Pract Concept     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-05-23     Completed Date:  2014-05-23     Revised Date:  2014-05-26    
Medline Journal Info:
Nlm Unique ID:  101585990     Medline TA:  Dermatol Pract Concept     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23-8     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Dermatol Pract Concept
Journal ID (iso-abbrev): Dermatol Pract Concept
Journal ID (publisher-id): DP
ISSN: 2160-9381
Article Information
Download PDF
Copyright: ©2014 Chen et al
Received Day: 26 Month: 9 Year: 2013
Accepted Day: 07 Month: 1 Year: 2013
collection publication date: Month: 4 Year: 2014
Electronic publication date: Day: 30 Month: 4 Year: 2014
Volume: 4 Issue: 2
First Page: 23 Last Page: 28
PubMed Id: 24855569
ID: 4029249
DOI: 10.5826/dpc.0402a04
Publisher Id: dp0402a04

Papillary adenocarcinoma in situ of the skin: report of four cases
Sheng Chen1
Masoud Asgari2
1Department of Pathology and Laboratory Medicine and Department of Dermatology, Hofstra North Shore-LIJ School of Medicine, NY, USA
2Department of Pathology and Laboratory Medicine, Staten Island University Hospital, NY, USA
Correspondence: Corresponding author: Sheng Chen, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School of Medicine, 6 Ohio Drive, Suite 202, Lake Success, NY 11042, USA. Tel. 516.304.7284; Fax. 516.304.7270. Email.


In general, epithelial neoplasm can be classified into three categories, namely, benign neoplasm, carcinoma in situ (noninvasive carcinoma) and invasive carcinoma. When the term carcinoma used unmodified, it generally refers to invasive carcinoma. However, since the introduction of the concept of carcinoma in situ by Broder in 1932 [1], there have been only occasional case reports of adenocarcinoma in situ of skin in the literature [26]. Adenocarcinoma in situ of skin as a concept and as a diagnostic category has not been established in the field of dermatopathology [79]. In this essay, four cases of papillary adenocarcinoma in situ (PACIS) of skin are reported. Furthermore, the notion that lesions previously reported in the medical literature under the term of papillary eccrine adenoma are actually PACIS is discussed.

Materials and methods
Case history
Case 1

The patient was a 82-year-old female with a 1.2 cm painful mass in her right second toe. The lesion was excised and diagnosed by a dermatopathologist as sweat duct carcinoma, involving the specimen margins. Subsequently, amputation of the right second toe was performed. Upon review of the amputation specimen along with the prior excision specimen, another dermatopathologist in a different institution interpreted the lesion as papillary eccrine adenoma.

Case 2

The patient was a 47-year-old female with a 1.5 cm skin nodule on her right leg. The lesion was excised and was reported to be adenocarcinoma with negative margins.

Case 3

The patient was a 43-year-old male, who presented with a 1.4 cm lesion on his right index finger. The lesion was excised and reported as papillary eccrine carcinoma in situ. Subsequently the patient requested a second opinion from two dermatopathologists from two separate institutions, who both interpreted the lesion as aggressive digital papillary adenocarcinoma.

Case 4

The patient was a 68-year-old female with 1.8 cm nodule in her right leg. The nodule was excised and interpreted as eccrine carcinoma in situ extending to surgical margin. Re-excision was performed and showed focal residual tumor with negative surgical margin. One month earlier, the patient had right breast mastectomy with sentinel lymph node biopsy, which showed the presence of a 3.0 cm low-grade invasive ductal carcinoma with mucinous features in the breast. Four sentinel lymph nodes were negative for tumor. Two years later, the patient had radical right hemicolectomy for a 10.5 cm moderately to poorly differentiated adenocarcinoma of the cecum with 5/17 positive lymph nodes and liver metastasis.

The clinical summaries of the four cases are listed in Table 1.


Histopathologic and immunocytochemical features: By light microscopy, the tumors in all our cases consisted of circumscribed but not encapsulated intradermal proliferations of variously-sized tubules and ducts embedded in a sclerotic stroma (Figures 1 and 2). Many of them were lined by a double layer of cells. The outer layer composed of flattened myoepithelial cells. The inner cells were cuboidal to columnar and formed in most lumens papillary projections. Squamous metaplasia was also noted in one case. Cytologically, the cells showed mild to moderate nuclear atypia. Mitotic figures and single cell necrosis were noted. An intact myoepithelial layer was evident on H&E-stained sections of all four cases and this was further confirmed by immunohistochemistry for P63, which was performed on two cases (Cases 2 and 3), and revealed strong positive reaction in outer layer (Figure 3A). Ki-67 staining was performed on one case (Case 3) and was positive in at least 30% of neoplastic cells (Figure 3B). Various diagnoses ranging from papillary eccrine adenoma, carcinoma in situ, and carcinoma were rendered by different pathologists or dermatopathologists (Table 2).


Since the introduction of the concept of carcinoma in situ in 1932 [1], although rare cases of adenocarcinoma in situ of the skin have been reported [26], adenocarcinoma in situ of the skin as a concept and as a diagnostic category has not been established [79]. Conceptually cases of adenocarcinoma in situ of skin must exist. The four cases presented here, in our opinion, are such examples. These lesions show cytological malignancy (nuclear atypia, single cell necrosis and mitotic figures) with intact myoepithelial cell layer (no evidence of invasion), fulfilling the criteria for carcinoma in situ set forth by Broder in 1932 [1]. If one employs the diagnostic criteria of breast pathology, these lesions are morphologically identical to the micropapillary type of ductal carcinoma in situ in the breast [10]. Although these cases were variably interpreted as invasive adenocarcinoma, they are obviously not invasive adenocarcinoma because of the presence of an intact myoepithelial cell layer. The main reason they were interpreted as invasive adenocarcinoma is that cutaneous adenocarcinoma in situ has not been established as a diagnostic category or entity. When pathologists encounter these kinds of lesions, they would classify them either as adenoma or invasive adenocarcinoma.

In 1973, Panet-Raymond and Johnson described a very similar lesion under the term of adenocarcinoma of the eccrine sweat gland [11]. They reported a case of a 49-year-old man who had a slow growing tumor on his left forearm since childhood. The tumor rapidly began to grow and for this reason it was excised. The histopathologic features were deemed by the authors to be adenocarcinoma of the sweat gland. However, based on what the authors described and illustrated microscopically in their article, the lesion is identical to the cases presented here. They called it carcinoma “on the basis of non-encapsulation, areas of intracystic papillary projections, and the presence of hyperchromatic nuclei, a moderate number of mitoses and some atypical cells in these latter areas.”

We believe that lesions reported under the term papillary eccrine adenoma are not adenoma but PACIS. In 1977, Rulon and Helwig described an identical lesion but named it for the first time “papillary eccrine adenoma” [12]. They reported on 14 cases of distinctive cutaneous glandular neoplasm, which they stated, “were difficult to interpret and had been believed to occupy the gray zone separating benign and malignant neoplasms of the sweat glands. Since none was found to have metastasized, this lesion is provisionally considered benign. The diagnostic term of papillary eccrine adenoma is suggested.” The lesions varied in size from 0.5 to 2.0 cm and could be found in any part of the skin including fingers and toes. Histologically the lesions they described are very similar, if not identical, to the four cases described here in the present study. Regarding treatment and nature of the lesions, Rulon and Helwig stated “surgical excision with assurance of complete removal by histologic examination of the surgical margins is considered the treatment of choice. The lesion is considered benign on the basis of available follow-up information.” As one can see, Rulon and Helwig considered the lesions benign, namely, papillary eccrine adenoma, based on no recurrence or metastases following complete surgical excision or digital amputation. However, this does not argue against the notion that the lesions were actually adenocarcinoma in situ, since carcinoma in situ would behave exactly the same way, namely, no recurrence or metastases following complete surgical excision.

Subsequent studies using the term papillary eccrine adenoma have been published by different authors, but the majority of them are single case reports or a small series of cases [1330]. Very few authors questioned the true nature of the lesion under discussion and most simply followed Rulon and Helwig and considered their own cases as adenomas.

In 1987, Urmacher and Lieberman reported four cases using the term of papillary eccrine adenoma [31]. They did mention that three patients were seen prior to 1977 and diagnosed with sweat gland carcinoma. Because the histology in all four cases was similar to what Rulon and Helwig described as papillary eccrine adenoma in 1977, they reassessed the diagnosis and described them with the term papillary eccrine adenoma. Aloi and Pich admitted difficulty in differentiating between papillary eccrine adenoma and low-grade sweat gland carcinoma [32].

In all the above examples, we think the confusion was due to unawareness of adenocarcinoma in situ as a concept and as one diagnostic category in the skin.

In 2003, Denianke and Ackerman published an article and claimed that the so-called papillary eccrine adenoma is really apocrine papillary carcinoma [33]. Although we agree with Denianke and Ackerman that the so-called papillary eccrine adenoma is not adenoma, namely, a benign glandular neoplasm, we believe for the reasons stated above that the lesion under discussion is best categorized as PACIS, not carcinoma, which when used unmodified generally means invasive carcinoma.

Of note, our Case 3 was interpreted as aggressive digital papillary adenocarcinoma by two dermatopathologists from two independent institutions. This is not surprising, since to our knowledge at least two similar cases, which were reported as aggressive digital papillary adenocarcinoma in the literature, are actually adenocarcinoma in situ in our opinion. One case appeared in an article published in 2006 by Crowson et al [34]. The authors illustrated a case (figures 15 and 16 in the article) under the term digital papillary adenocarcinoma and commented that histopathologically the lesion was “cognate to that of ductal carcinoma in situ of the breast.” From the photomicrographs illustrated there, it appears that an intact peripheral myoepithelial cell layer was present, so we believe the case is actually adenocarcinoma in situ rather than digital papillary adenocarcinoma. The other case was presented in an article in 2010 by Hsu et al [35]. The authors described an 8 mm nodule on the finger of a 28-year-old woman diagnosed as aggressive digital papillary adenocarcinoma. According to the authors, the lesion was excised with a positive margin, and there was no evidence of disease progression at the six-year follow-up. The photomicrographs of H&E and P63 stain provided by the authors for their case (figures 2 and 3 in the article) showed clearly the presence of an intact myoepithelial cell layer. This led us (M.A. and S.C.) to conclude that the lesion actually represented so-called papillary eccrine adenoma (PACIS in our current opinion, see above) misinterpreted as aggressive digital papillary adenocarcinoma [36].

Of interest, in a recent book published in 2012 titled Cutaneous Adnexal Tumors by Kazakov et al., in the pages regarding digital papillary adenocarcinoma the existence of adenocarcinoma in situ is mentioned briefly in these words: “In several cases, the authors have noticed that a constant feature is the presence of a recognizable myoepithelial cell layer around the glands and sometimes at the peripheral of the cystic-papillary areas. Invasion into the stroma is sometimes seen and no myoepithelial cells are present in the invasive foci. On the contrary, the authors have encountered a case in which the whole lesion was endowed with a peripheral myoepithelial cell layer consistent with the concept of carcinoma in situ” [37]. In our opinion, this is probably the first time adenocarcinoma in situ was ever mentioned in the acral location.

Is PACIS eccrine or apocrine origin? Rulon and Helwig thought it of eccrine origin [12], while Denianke and Ackerman of apocrine origin [33]. Other authors pointed out a bimodal differentiation, to wit, originating from both apocrine and eccrine (apoeccrine) origin [38]. We believe that PACIS can derive from eccrine as well as apocrine glands. Currently there are no reliable histological or immunocytochemical features that can distinguish it for sure. For practical purposes, there is really no need to distinguish them. It does not matter clinically whether it is of eccrine or apocrine origin. It should be treated the same way, namely, simple complete but conservative excision. Thus, we would suggest using the term PACIS without using either of the modifiers eccrine or apocrine.


fn1-dp0402a04Funding: None.

fn2-dp0402a04Competing interests: The authors have no conflicts of interest to disclose.

fn3-dp0402a04All authors have contributed significantly to this publication.

1.. Broders AC. Carcinoma in situ contrasted with benign penetrating epitheliumJAMAYear: 1932992016704
2.. Castro CY,Deavers M. Ductal carcinoma in-situ arising in mammary-like glands of the vulvaInt J PatholYear: 20012027783
3.. Castelli E,Wollina U,Anzarone A,et al. Extramammary Paget disease of the axilla associated with comedo-like apocrine carcinoma in situAm J DermatopatholYear: 200224351712142618
4.. Obaidat NA,Awamleh AA,Ghazarian DM. Adenocarcinoma in situ arising in a tubulopapillary apocrine hidradenoma of the peri-anal regionEur J DermatolYear: 200616576817101482
5.. Shah SS,Adelson M,Mazur MT. Adenocarcinoma in situ arising in vulvar papillary hidradenoma: report of 2 casesInt J Gynecol PatholYear: 200827453618580327
6.. Weinreb I,Bergfeld WF,Patel RM,Ghazarian DM. Apocrine carcinoma in situ of sweat duct originAm J Surg PatholYear: 200933155718971780
7.. LeBoit PE,Burg G,Weedon D,et al. Pathology and Genetics of Skin Tumours (IARC WHO Classification of Tumours)LyonIARCPressYear: 2006
8.. Weedon D. Skin Pathology8th edNew YorkElsevierYear: 2010
9.. Elder D,Elenitsas R,Johnson BL Jr,et al. Lever’s Histopathology of the Skin9th edPhiladelphiaLippincott Williams & WilkinsYear: 2005
10.. Rosen PP. Rosen’s Breast Pathology3rd edPhiladelphiaLippincott Williams & WilkinsYear: 2009
11.. Panet-Raymond G,Johnson WC. Adenocarcinoma of the eccrine sweat glandArch DermatolYear: 19731079464264700
12.. Rulon DB,Helwig EB. Papillary eccrine adenomaArch DermatolYear: 19771135968857729
13.. Elpern DJ,Farmer ER. Papillary eccrine adenomaArch DermatolYear: 19781141241677931
14.. Sina B,Dilaimy M,Kallayee D. Papillary eccrine adenomaArch DermatolYear: 1980116719207377809
15.. White SW,Rodman OG. Papillary eccrine adenomaNatl Med AssocYear: 1982745736
16.. Cooper PH,Frierson HF. Papillary eccrine adenomaArch Pathol Lab MedYear: 19841085576546338
17.. Falck VG,Jordaan HF. Papillary eccrine adenoma. A tubulopapillary hidradenoma with eccrine differentiationAm J DermatopatholYear: 1986864723518523
18.. Kanitakis J,Hermier C,Thivolet J. Papillary eccrine adenomaAm J DermatopatholYear: 19881018022853581
19.. Sexton M,Maize JC. Papillary eccrine adenoma. A light microscopic and immunohistochemical studyJ Am Acad DermatolYear: 1988181114203290282
20.. Tellechea O,Truchetet F,Grosshans E. Papillary eccrine adenoma [Portuguese]Med Cutan Ibero Lat AmYear: 19891785912666801
21.. Jerasutus S,Suvanprakorn P,Wongchinchai M. Papillary eccrine adenoma: an electron microscopic studyJ Am Acad DermatolYear: 198920111142754059
22.. Hashimoto K,Kato I,Taniguchi Y,et al. Papillary eccrine adenoma. Immunohistochemical and ultrastructural analysesJ Dermatol SciYear: 1990165712100547
23.. Requena L,Peña M,Sánchez M,Sánchez Yus E. Papillary eccrine adenoma—a light-microscopic and immunohistochemical studyClin Exp DermatolYear: 19901542582279339
24.. Megahed M,Hölzle E. Papillary eccrine adenoma. A case report with immunohistochemical examinationAm J DermatopatholYear: 19931515058494116
25.. Biernat W,Kordek R,WoŸniak L. Papillary eccrine adenoma—a case of cutaneous sweat gland tumor with secretory and ductular differentiationPol J PatholYear: 199445319227697336
26.. Mizuoka H,Senzaki H,Shikata N,Uemura Y,Tsubura A. Papillary eccrine adenoma: immunohistochemical study and literature reviewJ Cutan PatholYear: 19982559649508346
27.. Guccion JG,Patterson RH,Nayar R,Saini NB. Papillary eccrine adenoma: an ultrastructural and immunohistochemical studyUltrastruct PatholYear: 19982226399793207
28.. Kurtz DH,Finnell JA,Mehler AS. Papillary eccrine adenoma of the heel: a case reportJ Foot Ankle SurgYear: 2000392495210949805
29.. Blasini W,Hu S,Gugic D,Vincek V. Papillary eccrine adenoma in association with cutaneous hornAm J Clin DermatolYear: 200781798217492846
30.. Laxmisha C,Thappa DM,Jayanthi S. Papillary eccrine adenomaIndian J Dermatol Venereol LeprolYear: 200470370217642667
31.. Urmacher C,Lieberman PH. Papillary eccrine adenoma. Light-microscopic, histochemical, and immunohistochemical studiesAm J DermatopatholYear: 1987924393631452
32.. Aloi F,Pich A. Papillary eccrine adenoma. A histopathological and immunohistochemical studyDermatologicaYear: 199118247512013355
33.. Denianke K,Ackerman AB. The issue of eccrine versus apocrine differentiation of cutaneous neoplasms affiliated with tubules, Dermatopatholology: Practical & ConceptualYear: 200394
34.. Crowson AN,Magro CM,Mihm MC. Malignant adnexal neoplasmsMod PatholYear: 2006Suppl 2S9312616446719
35.. Hsu HC,Ho CY,Chen CH,et al. Aggressive digital papillary adenocarcinoma: a reviewClin Exp DermatolYear: 201035113919874325
36.. Asgari M,Chen S. Papillary eccrine adenoma should not be mistaken for aggressive digital papillary adenocarcinomaClin Exp DermatolYear: 201439223424274672
37.. Kazakov DV,Michal M,Kacerovska D,et al. Cutaneous Adnexal TumorsPhiladelphiaLippincott Williams & WilkinsYear: 20129599
38.. Fox SB,Cotton DW. Tubular apocrine adenoma and papillary eccrine adenoma. Entities or unity?Am J DermatopatholYear: 199214149541566975

Article Categories:
  • Observation

Keywords: papillary eccrine adenoma, adenocarcinoma in situ, aggressive digital papillary adenocarcinoma, eccrine gland, apocrine gland.

Previous Document:  Papulonecrotic tuberculid-clinicopathologic and molecular features of 12 Indian patients.
Next Document:  Tufted hemangioma: clinical case and literature review.