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Case Report
Case report and literature review: Management of squamous cell carcinoma in
situ of the nipple
Anne Bowers
*
, Alexandra Monteverde, Alan Heimann, Edna Kapenhas, Antoinette Notaro
Ellen Hermanson Breast Center, Southampton, NY, USA
article info
Article history:
Received 22 August 2017
Received in revised form
2 September 2017
Accepted 2 September 2017
Available online 14 September 2017
1. Introduction
Squamous cell carcinoma (SCC) of the nipple is extremely
rare and has only been documented in the English literature in
twelve separate case reports found after an extensive literature
search. There were no consistent risk factors amongst those
reports but pertinent risk factors include personal history of
breast cancer, history of breast radiation therapy, extensive sun
exposure, pregnancy, HIV, human papilloma virus, and history of
tongue cancer. Of the twelve case reports, three were male and
nine were female. The overwhelming majority presented with a
scaly rash of the nipple with the exception of four cases, one
with fungating mass, one with nipple nodule, one with exo-
phytic mass and the other with non-healing ulceration. The
outcomes after follow up were excellent with eight of the pa-
tientsreportedasdiseasefreeafteratimeperiodrangingfrom
six months to five years. The other four case reports did not
describe any follow up results. In our case, we describe a squa-
mous cell carcinoma in situ of the nipple in an elderly female
with a history of one year of intermittent nipple urticaria and
erythema. This case report and literature review was written to
show how to recognize a rare disease process and to treat the
patient in a manner which is safe, effective and has a satisfactory
outcome. Our patient had the common presentation of a nipple
rash which was biopsied and proved to be squamous cell car-
cinoma in situ. She was treated with Moh' surgery and has been
disease-free since the surgery as well as aesthetically pleased
with the minimally invasive outcome. This case report follows
the SCARE guidelines [14].
2. Case presentation
A72 year-old female presented to our breast clinic with primary
complaint of right nipple redness, itching and pain. She had
recently been prescribed Doxycycline and Betamethasone cream by
an Urgent Care center a couple of weeks prior with no improve-
ment of her symptoms. The patient also stated that she had an
approximately one year history of “flare ups”of her nipple with
redness and itching that resolved spontaneously. At one point, she
did have a biopsy by her dermatologist of the right medial breast for
the same symptoms with pathology of spongiotic superficial peri-
vascular and interstitial dermatitis with eosinophils consistent
with contact dermatitis or insect bite. She has not had a biopsy of
the right nipple. Recent bilateral mammography was benign (BIR-
ADS II). The patient's Gail model risk was calculated as 5.2% five-
year risk and13% lifetime risk. The patient's history was signifi-
cant for a mother with postmenopausal breast cancer. Her past
medical history included hypercholesterolemia and mitral valve
prolapse She has no pertinent psychosocial history or history of
drug use. The patient has not had any genetic testing. On physical
exam, the right nipple was erythematous with no scaly rash pre-
sent. No lymphadenopathy was present. A punch biopsy, per-
formed by her dermatologist, of the right nipple revealed benign
reactive stromal changes with prominent lymphovascular changes
and mild perivascular lymphocytic inflammation.
Subsequently the symptoms improved and the nipple itching
had resolved with topical triamcinolone cream. A few months later,
the symptoms returned which prompted another nipple biopsy by
her dermatologist revealing squamous cell carcinoma in situ of the
right nipple (Fig. 1). The patient opted to undergo Moh's surgery
instead of wide local excision as she wanted optimal cosmetic
result in combination with disease free state. The lesion measured
43cm prior to Moh's surgery completed by her dermatologist.
The patient is now four years out from intervention with Moh's
surgery and has no evidence of recurrence. She has had resolution
of her symptoms as well as continued benign findings (BIRADS II)
on her mammograms. The patient has been pleased both physically
and emotionally with her results and continues to follow up on a
regular basis with routine mammograms. The patient did give
informed consent for this case report.
*Corresponding author.
E-mail address: anne.wills@lmunet.edu (A. Bowers).
Contents lists available at ScienceDirect
International Journal of Surgery Open
journal homepage: www.elsevier.com/locate/ijso
http://dx.doi.org/10.1016/j.ijso.2017.09.001
2405-8572/Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).
International Journal of Surgery Open 9 (2017) 10e12
3. Discussion
Squamous cell carcinoma is the second-most common skin
malignancy and is highly associated with sun-exposure to fair skin.
Because ionizing and ultraviolet radiation is a major risk factor for
squamous cell carcinoma, it often occurs on the head and neck.
Other risk factors include therapeutic radiation, human papilloma
virus infection, immune suppression, origin in chronic wounds or
scars, congenital diseases with higher sensitivity to UV light, and
certain chemicals like pesticides. Patients will present with a va-
riety of appearances of the skin including a raised pink papule or
plaque that may be scaly, crusted, or ulcerated. The skin may be flat,
cyst-like, horned, or deep and penetrating. The grading system
used for classification is the TNM system accounting for tumor size,
depth, lymphovascular invasion and metastases. Larger and/or
deeper lesions are more likely to metastasize as well as recur.
Metastases are most likely to occur at primary regional lymphatics.
Treatment of squamous cell carcinoma of the skin is based on the
high versus low risk nature of the tumor. Options include cryo-
therapy or surgical excision with histologic margin for small, low
risk tumors. Radiation therapy may be attempted if the patient
cannot tolerate surgery. For high-risk tumors, a multidisciplinary
approach is warranted [7].
The twelve cases of squamous cell carcinoma reviewed in the
literature differed in presentation, risk factors, and management
(Table 1). Each case was confirmed with punch biopsy prior to
definitive treatment. One case presented a 34 year-old female with
scaly lesion of the nipple who underwent excisional biopsy and has
been disease free for twelve months [1]. The next case was an 87
year-old female who underwent modified radical mastectomy,
(which included isolation of eleven lymph nodes negative for ma-
lignancy), after presenting with a fungating mass of the nipple [2].
Another female, 66 years-old, African American, presented with
abnormal enhancement of the nipple on MRI ten years after breast
conservation surgery and radiation for ductal carcinoma in situ of
the ipsilateral breast. She underwent wide excisional biopsy and
was lost to further follow-up [3]. A 29 year-old pregnant female has
been disease free for fifteen months after presenting with a nodule
of the nipple and undergoing wide local excision with regional
lymph node dissection [4]. A 41 year-old HIV and HPV positive male
presenting with scaly lesions of the nipple has been disease free for
three years after a simple mastectomy with sentinel lymph node
biopsy [5]. Another case, a 58 year-old female with history signif-
icant for tongue cancer status post-surgical excision and chemo-
therapy presented ten years later with a crusted eschar of the
nipple. She was treated with simple mastectomy and sentinel
lymph node biopsy. Her follow up is not reported [6]. A 67 year-old
female presenting with exophytic mass was treated with mastec-
tomy and axillary lymph node dissection and is reported disease
free at five years [8]. Another presentation of scaly rash in an 84
year-old female underwent wide local excision and has been dis-
ease free for thirty months [9]. A 76 year-old male with unknown
risk factors was treated with wide local excision after presenting
with scaly rash found to be squamous cell carcinoma. No follow up
reported [10]. One paper presented two interesting cases with good
follow up documentation. A 71 year-old female with history of
breast cancer and radiation was first treated with cryotherapy twice
when found to have squamous cell carcinoma and returned with
residual disease both times. Therefore, she underwent photody-
namic therapy and became disease free for nine months. The other
case was a 69 year-old female with unknown risk factors presenting
with scaly rash found to be squamous cell carcinoma and treated
with wide local excision twice before being reported as disease free
for six months [11]. The last patient found after extensive literature
review was a 62 year-old male with history of ten years of sun
exposure to the breasts presenting with scaly lesion of the nipple
treated by wide local excision and subsequently lost to follow up
[13].
The choice of therapy in treating SCC should be assessed on a
patient-to-patient basis; with the primary goal of the treatment
being complete tumor eradication. Other goals of therapy should
include minimizing the risk of recurrence and metastasis, restoring
normal function after treatment and providing good cosmesis.
Other essential factors influencing the plan of care should include
Fig. 1. Squamous cell carcinoma in situ. Section shows full-thickness, high-grade
dysplastic cells without evidence of maturation. (200X).
Table 1
Squamous cell carcinoma of the nipple and areola details per case reports reviewed.
Age/Sex Presentation Risk factors Therapy Outcome
(*) 34yo Female [1] Scaly rash Unknown WLE DF X 12 months
(^) 87yo Female [2] Fungating mass Unknown Modified radical mastectomy DF X 5 years Unknown
(^) 66yo Female [3] Non healing ulcer Breast Cancer, XRT WLE Unknown
(^) 29yo Female [4] Nipple nodule Pregnant WLE þregional LN dissection DF X 15 months
(*) 41yo Male [5] Scaly rash HPV, HIV Mastectomy, SLNB DF X 3 years
(*) 58yo Female [6] Scaly rash Tongue Cancer; XRT Simple mastectomy with SLNB Unknown
(*) 67yo Female [8] Exophytic mass Unknown Mastectomy, ALND DF X 5 years
(*) 84yo Female [9] Scaly rash Unknown WLE DF X 30 months
(*) 76yo Male [10] Scaly rash Unknown WLE Unknown
(*) 71yo Female [11] Scaly rash Breast cancer, XRT Photodynamic &Cryotherapy Residual disease X 2; DF X 9 months
(*) 69yo Female [11] Scaly rash Unknown WLE Recurrence at 3 months; re- excision;
DF X 6 months
(*) 62yo Male [13] Scaly rash Sun exposure WLE Unknown
WLE ¼wide local excision; DF ¼disease free; XRT ¼radiation therapy; SLNB ¼sentinel lymph node biopsy; ALND ¼axillary lymph node dissection; HPV ¼human.
(*) denotes squamous cell carcinoma in situ; (^) denotes invasive squamous cell carcinoma.
A. Bowers et al. / International Journal of Surgery Open 9 (2017) 10e12 11
the patient's general medical condition and quality of life, location
of the tumor, and social components such as cost and likelihood of
follow-up [14].
Mohs Micrographic Surgery (MMS) is a technique utilized for
removal of complex or ill-defined skin cancers. It combines surgical
excision with histological exam of 100% of the peripheral and deep
surgical margins. The tumor tissue is removed, mapped and divided
into pieces, which are subsequently embedded into an individual
tissue block for histopathologic examination using either
hematoxylin-eosin or toluidine blue. It provides the best long-term
cure rate for SCC and because of its complete margin assessment; it
is also the treatment of choice for both high-risk and recurrent SCC.
Based on the Appropriate Use Criteria (AUC) guidelines, MMS is
appropriate for areas where maximal preservation of normal tissue
is preferred or required. Because MMS is a tissue-sparing technique,
smaller surgical margins are taken and scarring and functional
impairment are minimized compared with standard surgical exci-
sion (SSE) and Electrodesiccation and Curettage (ED&C). This in-
cludes, but is not limited to the face, ears, hands, feet, genitalia,
nipples/areola, and mucous membranes [14]. In a recent study done
at the University of Virginia Health System between May 2011 and
December 2011, they used the appropriate-use criteria to retro-
spectively evaluate the use of MOHs microsurgery on 1059 skin
cancers. They found tumor location to be the most important factor
to determine appropriate use. Of the 72% of skin cancers that met
criteria, 59.3% were areas including the head, neck, hands, feet,
ankles, genitalia, and nipples/areola [12].
Other benefits of Mohs procedure include low risk profile, good
cosmetic outcomes, and low cost. In a study done at Duke Univer-
sity during the year 2000, 1358 MMS cases were prospectively
enrolled, with complete follow-up information available for 1343
participants (98.9%). Of the 1358 participants enrolled, there were
only 22 reported incidents of post-op complication (1.64%) This
included 3 separate and isolated occurrences of day-of-surgery
hematoma, and 1 incidence of day-of-surgery hemorrhage; none
of which were severe enough to warrant overnight hospitalization.
All other complications were considered delayed complications
(>24 hours postop) and included graft/flap necrosis, hematoma,
postoperative hemorrhage and only 1 incidence of infection, and 1
incidence of wound dehiscence [15]. Because these procedures can
typically be done in the outpatient setting, costs are significantly
lower.
4. Conclusion
Although squamous cell carcinoma is a common disease pro-
cess, it is extremely rare to present on the nipple as in situ or
invasive disease. Only twelve case reports have been documented
in the English literature. Of the 12 reported cases, eight presented
with a scaly rash, one with a fungating mass, one with an exophytic
mass, one with a non-healing ulcer, and one with a nipple nodule.
Treatment options varied from cryotherapy (being the least inva-
sive) to modified radical mastectomy (being the most invasive)
with most patients opting for wide local excision. Eight out of the
twelve patients were reported disease free six months to five years
after diagnosis regardless of treatment modality. The other four
cases had no reported follow-up. Our patient presented with an
erythematous nipple, but no scaly rash. She is the first documented
case to be treated with MMS and has been disease free for four
years. Because of the patients' great response to treatment
regardless of the modality, we advocate that MMS should be
strongly considered for the treatment of squamous cell carcinoma
in situ due to its low invasive nature, quick recovery time, and
excellent long-term cure rate. In addition, MMS provides great
cosmetics, low cost, and can be performed in the outpatient setting.
This paper focused on a literature review of the various pre-
sentations, treatment considerations and long term outcomes of a
disease process that is uncommonly encountered with the goal of
consolidating the literature available to date to help guide practi-
tioners when a case of squamous cell carcinoma in situ is
encountered.
Disclaimer
There were three cases of invasive squamous cell carcinoma and
with the limited literature at this time, we exclude those cases from
our recommendations.
Conflict of interest
The authors declare that there is no conflict of interest regarding
the publication of this paper.
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