Keywords sebaceous cyst - mucinous adenocarcinoma - eccrine glands
Introduction
Primary mucinous carcinoma (PMC) of the eyelid is a rare uncommon neoplasm arising
from sweat glands, with an incidence of 1 per 150,000 population.[1 ] Due to lack of typical characteristics, it is often misdiagnosed as pilomatricoma,
chalazion, or epidermoid cyst before resection.[2 ] Clinically PMCs are indolent in nature; hence, these lesions are often unremarkable.
They are described grossly as pedunculated, fungating, or papillomatous.[3 ]
They commonly arise in the head and neck region, with the eyelid being the most common
site of origin.[4 ] It is more commonly seen in males and appears most frequently between the ages of
50 and 70 years.[5 ] Here, we report a case of PMC of the left upper eyelid in a 64-year-old man. They
are characterized by slow growth and local invasion with a high rate of recurrence.[6 ] On hematoxylin and eosin stain, PMC usually mimics metastatic carcinoma of the breast,
gastrointestinal (GI) tract, ovary, or lung origin, and create a diagnostic dilemma.
Case Report
A 64-year-old male patient presented in the outpatient department of ophthalmology
with a swelling over the middle part of the left upper eyelid. Initially swelling
was small and gradually increased to the present size over the course of 10 years
([Fig. 1 ]). He is a known diabetic for the past 15 years. On local examination, a mass measuring
2 × 2 cm was found over the left upper eyelid, which was nontender and had cystic
consistency without localized/generalized lymphadenopathy. The transillumination test
was positive. There was no history of weight loss. All routine hematological and biochemical
tests were within normal limits. Gastrointestinal endoscopy was done, which was normal.
Computed tomography of the head and neck, chest, abdomen, and pelvis revealed no lymph
node or distant metastases.
Fig. 1 Clinical image showing polypoidal lesion on the left upper eyelid.
Excision biopsy with lid reconstruction was performed and sent for histopathological
examination. Gross examination revealed a partially skin-covered irregular soft tissue
mass measuring 1 × 1 × 0.5 cm in size. On microscopic examination, sections showed
epidermis with dermis having a poorly circumscribed tumor consisting of predominantly
large pools of basophilic mucin compartmentalized by delicate fibrous septa with floating
islands of neoplastic epithelial cells within the pools of mucin. These tumor cells
were arranged in tubular and cribriform patterns. Individual tumor cells had scant
cytoplasm with hyperchromatic round nuclei and mild atypia ([Fig. 2 ]). There was no tumor necrosis, and lymphovascular and perineural invasion. Resected
margins were negative for tumor involvement. Periodic acid–Schiff (PAS) stain was
positive for mucin pools ([Fig. 3 ]). Immunohistochemically the tumor was positive for estrogen receptor (ER), progesterone
receptor (PR), and pancytokeratin AE1/AE3 immunohistochemical markers ([Fig. 4 ]). Based on all the findings, a final diagnosis of primary mucinous tumor of eyelid
with stage IA was made. No recurrence was discerned at follow-up examination 6 months
later.
Fig. 2 (a ) Microscopy showing a well-circumscribed tumor consisting of cells in pools of mucin:
hematoxylin and eosin (H&E), ×100. (b ) Individual tumor cells had scant cytoplasm with hyperchromatic round nuclei and
mild atypia: H&E, ×400.
Fig. 3 Periodic acid–Schiff (PAS) stain showing mucin positivity (×400).
Fig. 4 Immunohistochemical staining of tumor cells showing (a ) estrogen receptor positivity (×200), (b ) progesterone receptor positive (×400), and (c ) PanCK AE1/AE3. Positive (×200).
Discussion
PMC is a very rare slow-growing tumor that was first described in 1952 by Lennox et
al with an incidence of 1 per 150,000 population. They primarily affect middle-aged
or older individuals, with 54.7 to 70% of cases occurring in men and periorbital involvement
observed in 40 to 49.7% of cases. It is a slow-growing, small, flesh-colored or pale
blue, smooth nodule. Because of the lack of typical characteristics, it is often misdiagnosed
as an epidermoid cyst, pilomatrixoma, or chalazion before resection with subsequent
enucleation performed unintentionally.[1 ]
[2 ]
[5 ] It is a malignant tumor of sweat gland origin, with 40% of the cases originating
periorbitally. It is a locally destructive tumor infiltrating into the muscle, orbital
fat, and bone with frequent recurrence but rare metastasis.[7 ] In the present case, the patient is 64-year-old.
Although it was controversial and debate exists whether it arises from eccrine or
apocrine differentiation, most authors favor the eccrine differentiation based on
the evidence from the immunohistochemical studies and structural analysis by electron
microscopy.[8 ]
Mucinous carcinoma rarely originates in the skin and the majority are actually metastatic
to it.[9 ] Common sites of origin of mucinous carcinomas are the breast, gastrointestinal tract,
salivary glands, lacrimal glands, nose, paranasal sinuses, bronchi, renal pelvis,
and ovary.[10 ] The criterion to distinguish a primary from a secondary mucinous carcinoma is the
presence of an in situ component, which indicates a tumor with skin as its origin
because a metastatic carcinoma from a distant place cannot have an in situ component.
Moreover, since mammary neoplasms have a strong preference for the chest, breast,
and axilla, the location of the tumor may be useful in the differential diagnosis.
The PMC diagnosis in our case is supported by the tumor's location on the upper eyelid
and the presence of low-grade atypical cells.[11 ] Primary lesions can be differentiated from metastatic lesions by their more organized
epithelial cells and less hyperchromatic and fewer mitoses in individual cells. In
addition, in the case of metastatic carcinoma, tumor cells invade between the collagen
bundles at the margin of the nodule, which was not seen in our case.
PMCs are sharply circumscribed tumor in the dermis with no connection to the epidermis.
It should always be differentiated from sweat gland and sebaceous gland carcinomas.
On histopathology, PMC is composed of small clusters of tumor cells in ducts and trabeculae
floating in pools of basophilic extracellular mucin. The mucin is PAS positive.[11 ] This case also showed the same microscopic features.
It is important to distinguish from metastatic adenocarcinoma and it is mainly by
immunohistochemical profile. This case showed a strong expression for ER, PR, and
pancytokeratin. Since endoscopy and CT findings were normal, other markers like MUC1
and MUC5AC were not done.
Treatment of PMC is primarily surgical. The majority of morbidities in patients with
PMC are due to incomplete lesion resection.[10 ]
[11 ] The prognosis following local excision confirmed with tumor-free margins is good.
Several reports of successful treatment using Mohs micrographic surgery have been
described. The treatment of choice was excision in our case as well. Other treatments,
such as chemotherapy and radiation, are generally not employed in the management of
these tumors. Patients should be counseled about the importance of frequent follow-ups
for evaluation of local tumor recurrence or development of regional lymphadenopathy.
Conclusion
PMCs are rare challenging neoplasms and often resemble common lesions. The ophthalmologists
should be aware of this tumor due to its high recurrence rate and should consider
these carcinomas in the differential diagnosis of any cystic/solid lesion of the eyelid
in the periorbital region.
