Dermatology: Practical and Conceptual


DERMATOLOGY PRACTICAL & CONCEPTUAL
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Observation  |  Dermatol Pract Concept 2014;4(2):4 23

Introduction

In general, epithelial neoplasm can be classified into three 

categories, namely, benign neoplasm, carcinoma in situ (non-

invasive 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 [2-6]. Adenocarcinoma in situ of skin as a 

concept and as a diagnostic category has not been established 

in the field of dermatopathology [7-9]. 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 inter-

preted the lesion as papillary eccrine adenoma.

Case 2
The patient was a 47-year-old female with a 1.5 cm skin nod-

ule on her right leg. The lesion was excised and was reported 

to be adenocarcinoma with negative margins.

Papillary adenocarcinoma in situ of the skin: 
report of four cases

Sheng Chen1, Masoud Asgari2

1 Department of Pathology and Laboratory Medicine and Department of Dermatology, Hofstra North Shore-LIJ School of Medicine, NY, USA

2 Department of Pathology and Laboratory Medicine, Staten Island University Hospital, NY, USA

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

Citation: Chen S, Asgari M. Papillary adenocarcinoma in situ of the skin: report of four cases. Dermatol Pract Concept. 2014;4(2):4. http://
dx.doi.org/10.5826/dpc.0402a04

Received: September 26, 2013; Accepted: January 7, 2013; Published: April 30, 2014

Copyright: ©2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: None.

Competing interests: The authors have no conflicts of interest to disclose.

All authors have contributed significantly to this publication.

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. schen@nshs.edu

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.

ABSTRACT

mailto:schen@nshs.edu


24 Observation  |  Dermatol Pract Concept 2014;4(2):4

The clinical summaries of the four cases are listed in 

Table 1.

Results

Histopathologic and immunocytochemical features: By light 

microscopy, the tumors in all our cases consisted of circum-

scribed 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).

Discussion

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 [2-6], adenocarcinoma in situ of the 

skin as a concept and as a diagnostic category has not been 

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.

 TABLE 1. Clinical summary of the four cases  

Case Age Sex
Lesion 

location
Lesion 

size

1 82 Female Right 2nd toe 1.2 cm

2 47 Female Right leg 1.5 cm

3 43 Male Right index 
finger

1.4 cm

4 68 Female Right leg 1.8 cm

Figure 1. Case 2, papillary adenocarcinoma in situ. (A) Low power view showing a circumscribed lesion located in a fibrotic dermis (H&E, 

x20); (B) Medium power view showing dilated ducts with prominent papillary projections (H&E, x100); (C) High power view showing 

clearly the presence of intact myoepithelial cell layer (H&E, x400). [Copyright: ©2014 Chen et al.]



Observation  |  Dermatol Pract Concept 2014;4(2):4 25

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 diag-

nostic 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 child-

hood. 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 micro-

scopically 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 papil-

lary 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 

established [7-9]. 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 

Figure 2. Case 3, papillary adenocarcinoma in situ. (A) Low power view showing a lesion in a fibrotic dermis (H&E, x40); (B) Medium 

power view showing prominent papillary structure formation (H&E, x 200); (C) High power view showing the presence of necrosis and 

peripheral myoepithelial cell layer (H&E, x400). [Copyright: ©2014 Chen et al.]

Figure 3. Case 3, papillary adenocarcinoma in situ. Immunocy-

tochemical stain for P63 (A, x400) and Ki67 (B, x400). P63 stain 

highlights the intact layer of myoepithelial cells. At least 30% of 

neoplastic cells are positive for Ki67. [Copyright: ©2014 Chen et al.]



26 Observation  |  Dermatol Pract Concept 2014;4(2):4

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 adenocarci-

noma 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 fin-

ger 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 

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 adenocarci-

noma 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 ade-

noma have been published by different authors, but the 

majority of them are single case reports or a small series of 

cases [13-30]. 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].

 TABLE 2. Diagnoses offered by different pathology/dermatopathology consultants

Case 1st opinion 2nd opinion 3rd opinion

1 Sweat duct carcinoma (by 
dermatopathologist)

Papillary eccrine adenoma 
(by dermatopathologist)

Not applicable

2 Adenocarcinoma (by 
pathologist)

Not applicable Not applicable

3 Papillary eccrine carcinoma in 
situ (by dermatopathologist)

Aggressive digital papillary 
adenocarcnioma (by 
dermatopathologist)

Aggressive digital papillary 
adenocarcnioma (by 
dermatopathologist)

4 Eccrine carcinoma in situ (by 
dermatopathologist)

Not applicable Not applicable



Observation  |  Dermatol Pract Concept 2014;4(2):4 27

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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 periph-

eral 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 Acker-

man of apocrine origin [33]. Other authors pointed out a 

bimodal differentiation, to wit, originating from both apo-

crine 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 immunocyto-

chemical features that can distinguish it for sure. For practi-

cal 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.

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