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INTRODUCTION
This case report refers to an elderly female patient who presented with a scalp tumor that was biopsied and diagnosed as well-differentiated mucinous adenocarcinoma with coincident margins. In a note, the pathologist recommended that an immunohistochemical study be performed to distinguish between primary mucinous carcinoma of the sweat glands of the skin and metastatic breast neoplasia.
Primary malignant neoplasms of the apocrine glands are rare, accounting for less than one percent of all primary malignant skin lesions1. Cutaneous apocrine carcinoma presents characteristics similar to those of cutaneous metastases from breast carcinoma. This is a rare case2 and it is very difficult to differentiate one from the other, whether by clinical history, anatomical pathology or even by immunohistochemical study.
The objective of this case report was to demonstrate this difficulty and the importance of differentiating the diagnosis between the tumor mentioned being primary to the sweat gland or being a metastasis of breast carcinoma.
METHODS
This is a descriptive, retrospective study with a qualitative approach, in the form of a clinical case report, carried out based on the records available in the patient’s medical records. Data were collected regarding the patient’s previous history, current history, diagnostic hypotheses, treatments performed, and complementary exams performed. The patient signed the informed consent form.
CLINICAL CASE
Information and clinical findings about the patient in report
Patient DG, female, 86 years old, white, widowed, living in the city of São Paulo, in the Brazilian state of São Paulo.
He reported that he sought the surgeon with a tumor lesion in the right occipital region of the scalp, measuring approximately 1 cm in diameter and with poorly defined margins (figure 1). He had a history of previous surgery to remove a tumor from this region two years earlier. His medical records include the pathological anatomy report from this previous intervention, which showed the diagnosis of well-differentiated mucinous adenocarcinoma with coincident margins. In a note, the pathologist recommended that an immunohistochemical study be performed to distinguish between primary mucinous carcinoma of the sweat glands of the skin and metastatic neoplasia, but there is no record that this was done at the time.
Now, in the presence of recurrence of the lesion, an ultrasound examination of the head and neck was requested for staging, which showed no changes. After this staging, the patient underwent surgery in a hospital environment to remove the lesion with margins (figure 2) and to perform an intraoperative pathological anatomy examination (frozen section examination) to evaluate the surgical margins.
In the new pathological anatomy examination performed, he described having received a lesion on the right occipital scalp consisting of an elliptical structure of skin, partially sectioned, measuring 4.0 x 1.9cm and 0.9cm in maximum thickness. On the skin surface, he presented a discreetly depressed and whitish lesion, measuring 2.4 x 1.5cm. In the cuts, the tissue is firm-elastic and grayish, evidencing a soft, reddish-brown nodular area measuring 0.9 x 0.7 x 0.6cm. The lesion is 0.2cm away from the deep surgical margin (figure 3). In macroscopy, the margins were previously stained and identified: superior (violet); inferior (blue); medial (green); lateral (orange); deep (red). Cassette specifications: A1 to A6 - lesion/medial/ lateral/deep margins: 1bl; A7 - superior/inferior margins: 1bl. All material was sent for microscopic examination.
Source: The Author.
Figure 3 Sequential sections of the surgical specimen showing a nodular lesion measuring 0.9cm in its largest axis, centered on the dermis and subcutaneous adipose tissue
Microscopically, the neoplasm presented atypical cells arranged in solid or tubular cohesive groups, immersed in abundant extracellular mucin, which comprised more than 90% of the lesion (figure 4). The nuclei demonstrated moderate atypia, sometimes with prominent nucleoli and occasional mitotic figures. The growth pattern of the lesion was predominantly expansive, reaching as far as the subcutaneous adipose tissue (Clark level V)3 (figure 5). No areas of neoplasia “in situ”, lymphovascular or perineural invasion were identified. The surgical margins were free.
Source: The Author.
Figure 4 Atypical neoplastic cells in solid cohesive clusters amid abundant extracellular mucin
Source: The Author.
Figure 5 panoramic image showing neoplastic involvement of the dermis and subcutaneous adipose tissue (Clark level V)
Immunohistochemical study was performed using an automated methodology in Autostainer Link 48 with antigen retrieval by moist heat (PT Link-Dako) and visualization through the EnVision FLEX system, in addition to the automated Ventana BenchMark GX methodology (Roche). Positive controls (internal and/or external) confirm the fidelity of the method. Microscopic examination revealed the following results for the antigens studied: Cytokeratin 7 (CK7) (OV-TL 12/30) Positive in areas; GATA3 (L50-823) Positive; Estrogen receptor protein (EP1) Positive (intense) in 90% of neoplastic cells; Progesterone receptor protein ( PgR 636) Positive (intense) in 70% of neoplastic cells; p63 (DAK-p63) Positive in foci; Cytokeratin 20 (CK20) (K20.8) Negative; Mammoglobin (304-1A5) Negative; CDX2 (DAK-CDX2) Negative; PAX8 (MRQ-50) Negative; Napsin A (MRQ-60) Negative; TTF1 (8G7G3/1) Negative; D2-40 ( podoplanin ) (D2-40) Negative. Thus, it was concluded that this type of neoplasia exhibited an immunohistochemical profile overlapping between the primary cutaneous form and the metastatic presentation of a primary lesion in the breast. It was recommended that a correlation with clinical data, imaging exams and surgical history be necessary in an attempt to define the primary site of this neoplasia.
This patient had no previous diagnosis of breast carcinoma and, given the diagnostic hypothesis of metastasis of carcinoma of mammary origin, she was referred to the mastology service, where she underwent consultation and examinations to screen for breast carcinoma. Given this situation, with immunohistochemistry compatible with mucinous carcinoma, with GATA 3 POSITIVE, ER 90%, RP 70% and P63 POSITIVE IN FOCUSES, the mastologist performed an investigation of the breasts and lower genital tract to rule out a secondary lesion. On physical examination, the patient did not present palpable nodules, her armpits did not present enlarged lymph nodes and the gynecological examination showed no evident alterations.
Breast ultrasound was also performed , with category B IRADS 2 and transvaginal ultrasound that showed a uterus characterized only in the cervical portion, measuring approximately 44x35x24mm , the left varum with a solid nodular formation of 12.8mm, left ovary measuring: 30x27x22mm; volume: 9.7cm3 and right ovary not characterized in the present study. Due to the nodular lesion described in the left ovary, the study was complemented by magnetic resonance imaging that showed the left varum with slightly increased dimensions at the expense of a solid nodule with partially defined limits, with discrete low signal on T2, hypovascularized and with restricted diffusion, measuring 2.3x1.5x1.3cm, of undetermined nature. The results of the tumor markers were as follows: Carcinoembryonic antigen ( CA125) equal to 18 U/mL ; Carcinoembryonic antigen ( CEA) equal to 4.1 ng/mL; Cancer antigen 15-3 (CA15-3) equal to 32.6 U/mL; and the tumor marker CA19-9 (CA 19-9) was equal to 14 U/mL . To complete, a Pap smear was performed and showed a class II result. The gynecologist was contacted and he informed that the nodular lesion in the left adnexa had existed for 12 years and that it had remained stable on the controls performed since then.
DISCUSSION
Primary mucinous carcinoma of the skin is an adnexal neoplasm originating from the sweat glands. Due to its rarity and the scarcity of studies on the subject, there is still controversy regarding its origin and pathophysiology. Although it is considered to be of eccrine lineage, approximately 50% of cases show apocrine differentiation when analyzed by electron microscopy4. It is believed that primary mucinous carcinoma of the skin develops from an “in situ” neoplasm, which can be identified in up to 70% of cases5,6.
The morphological presentation of this neoplasia is defined by the presence of epithelial neoplastic cells amid a significant amount of extracellular mucin. It can be classically classified as pure, when composed of more than 90% mucinous component, or as mixed, when there is an associated ductal component. The neoplastic cells generally present mild to moderate atypia, with few mitotic figures. In some cases, it is possible to identify a component of carcinoma “in situ” in PPMC, in which intraductal neoplastic cells are observed with preservation of the myoepithelial layer4,7.
In immunohistochemical studies, PPMCs are typically positive for CK7, low molecular weight cytokeratins , EMA, CEA, GATA3, estrogen receptor protein, and progesterone receptor protein (X,Z¹’³). In addition, they are usually negative for CK20 and CDX2. The HER2 oncoprotein is negative or, on rare occasions, weakly positive (1+). The use of myoepithelial markers, such as p63, calponin , and high molecular weight cytokeratins , can help identify the “in situ” component of the neoplasia4,5,8.
From the pathologist’s point of view, the morphological and immunohistochemical findings of PPCM are similar to those observed in primary mucinous carcinomas of the breast and in their metastatic spread to the skin. In this situation, the identification of an “in situ” component can be of great help in defining the diagnosis, since it proves its cutaneous origin. However, the absence of “in situ” neoplasia does not exclude the diagnosis of PPCM and, in these cases, it is essential to perform an extensive correlation with clinical data, imaging exams and to investigate the breast to determine the primary site of the lesion. In this context, the absence of “in situ” carcinoma in the present case can be attributed to the fact that the lesion in question was a recurrence of the tumor previously subjected to surgical intervention. In addition, the negativity of PPCM for CK20 and CDX2, in contrast to their positivity in mucinous carcinomas of the intestine metastatic to the skin, is a crucial aspect for excluding this differential diagnosis4,5,6.
Therefore, to differentiate them, anamnesis, the patient’s clinical data and imaging tests are important, especially if the patient has a previous history of breast carcinoma or confirmation of a primary lesion in the breast9,10.
CONCLUSION
Primary mucinous carcinoma of the skin is an adnexal neoplasm originating from the sweat glands, and its origin and pathophysiology are still controversial due to its rarity and lack of studies. Its morphological presentation is characterized by the presence of neoplastic epithelial cells amidst extracellular mucin, and it can be classified as pure or mixed. Immunohistochemical studies reveal positivity for CK7, EMA, CEA, among others, and negativity for CK20 and CDX2. The identification of an “in situ” component can be crucial in the diagnostic differentiation, as it suggests primary cutaneous neoplasia. However, the absence of this component does not exclude the diagnosis, and an extensive correlation with clinical data and imaging exams is necessary for a better diagnostic conclusion regarding the primary site of the neoplasia, especially with emphasis on the differential with primary mucinous carcinomas of the breast and its metastatic spread to the skin.
