TRPS1::PLAG1 Fusion in a Primary Cutaneous Myoepithelial Carcinoma: A Case Report and Literature Review

ABSTRACT

Myoepithelial neoplasms are rare tumors that are found in the salivary glands, the breast, soft tissue, and skin. Myoepithelial carcinomas typically have a poor prognosis with a high rate of local recurrence and metastasis in the cutaneous setting. There are fewer than 30 described cases of primary cutaneous myoepithelial carcinoma in the literature. We performed a literature review and identified 26 known cases of primary cutaneous myoepithelial carcinoma. Here, we describe a case of occipital primary cutaneous myoepithelial carcinoma occurring in a 56‐year‐old patient. RNA sequencing was performed on the tumor which identified a TRPS1::PLAG1 fusion event which is to our knowledge, the first time this has been reported in the literature for a primary cutaneous myoepithelial carcinoma.

1. Introduction

Myoepithelial neoplasms arise in salivary glands, the breast, soft tissue, and skin. Among these sites, primary cutaneous myoepithelial neoplasms are rare. The tumor exists on a spectrum from benign myoepithelioma, to myoepithelial carcinoma [1]. The histopathology of myoepithelial neoplasms is broad, ranging from an epithelioid to spindled morphology, with reticular to trabecular growth patterns. Some tumors demonstrate a minor ductal component that closely resembles their salivary gland mixed tumor counterparts. By immunohistochemistry, the majority of the tumors are positive for broad‐spectrum keratins, S100 protein and calponin [2]. The only reliable features that distinguish a benign myoepithelioma from a myoepithelial carcinoma include moderate to severe nuclear pleomorphism and a high mitotic rate.

To‐date there are fewer than 30 primary cutaneous myoepithelial carcinomas reported in the literature [3]. These tumors occur equally in men and women and typically present in the 5th to the 6th decade of life. In the soft tissue setting, they are commonly associated with oncogenic EWSR1 RNA fusion events, followed by FUS fusions [4]. While mixed tumors and benign myoepitheliomas in the soft tissue have a relatively indolent course, myoepithelial carcinomas are associated with recurrence and metastases in upwards of 40%–50% of cases [5]. Unfortunately, this is closely mirrored in the cutaneous setting, and patients may present with metastases and regional lymph node involvement at the time of diagnosis [3].

2. Case Report

A 56‐year‐old man was referred to our clinic with a 6‐year history of a slowly enlarging asymptomatic occipital, cutaneous mass. Physical exam revealed a 15 cm firm tumor on the occipital area (Figure 1). There was no regional lymphadenopathy on physical exam, and he did not have any constitutional symptoms concerning for metastases. An initial biopsy revealed a dermal‐based myoepithelial neoplasm, composed of spindled and focally plasmacytoid cells within a fibrillary matrix. A diagnosis of myoepithelial neoplasm was rendered. A staging soft‐tissue CT scan of his head and neck was performed following the initial biopsy which showed parotid gland hypertrophy and lymphadenopathy. A follow‐up fine needle aspirate of the patient's parotid was performed which was negative for malignancy.

FIGURE 1.

Clinical photograph of the occipital, ulcerated mass measuring 15 cm in maximum dimension.

The patient underwent surgical resection of the tumor. Histopathological examination demonstrated a relatively circumscribed and dermal‐based tumor with extension into both the epidermis and subcutaneous tissue. The tumor was composed of cells with a predominance of spindled to epithelioid morphology with occasional foci of ductal differentiation set within a collagenous/chondromyxoid matrix (Figure 2). Mitoses were numbered at 5 mitotic figures/high‐powered field; there was moderate nuclear pleomorphism present and there were areas of cystic degeneration and necrosis. The resection margins were negative for malignancy.

FIGURE 2.

(A) Hematoxylin and eosin (H&E) stain of a representative section of the resection specimen denoting cystic degeneration and infiltrative borders (40×). (B) CK7 immunohistochemical stain of a representative section (40×). (C) Area of ductal differentiation within the tumor (H&E, 200×). (D) p63 immunohistochemical stain of a representative section (40×). (E) Area of brisk mitotic activity and discohesive, epithelioid cells with atypia and atypical mitoses within the tumor (H&E, 400×). (F) S100 immunohistochemical stain of a representative section (40×).

Immunohistochemistry showed positivity for AE1/AE3, CK5/6, CK7 (patchy), EMA (ductal component), GFAP (patchy), INI1 (intact), p63, S100 (patchy), and SOX10. SMA and GFAP showed focal/patchy staining throughout the tumor. The Ki‐67 proliferative index was 15%. The tumor was negative for CK20, Desmin and MelanA. AB/PAS highlighted areas consistent with chondromyxoid stroma.

A pan‐solid tumor RNA fusion panel was performed on the tumor tissue using the Ion Torrent Genexus System platform. A TRPS1::PLAG1 (exon 1 at genomic position chr8:g.116680772 in the TRPS1 gene and within the PLAG1 gene in exon 2 at genomic position chr8:g.57092072) fusion was identified which has been previously associated with adnexal carcinomas, uterine leiomyosarcomas and myoepithelial neoplasms [6, 7, 8]. Given the above immunohistochemistry, histomorphology and sequencing features, the diagnosis was favored to represent a primary cutaneous myoepithelial carcinoma arising in a mixed tumor. Following surgical resection, the patient underwent local radiotherapy treatment of 60 gray in 30 fractions. At 26 months of follow‐up, there was no clinical evidence of local recurrence, and a soft‐tissue CT of the head and neck was also negative for recurrence. Informed consent for the case report was obtained directly from the patient in writing.

3. Literature Review

We identified 26 cases of primary, cutaneous myoepithelial carcinoma in the literature (we included cases of “malignant myoepithelioma” and “myoepithelioma with malignant features” which fit the histopathological features suggestive of malignancy as described in the 5th edition of the Bone and Soft Tissue WHO Blue Book). The age of patients diagnosed with primary cutaneous myoepithelial carcinoma ranged from 21 days old to 85 years of age with a median age of 58 years (Table 1). The proportion of males to females was approximately 1:1. The mean age at the time of diagnosis was 50.56 years (standard deviation ±24.70 years). Most patients were treated with primary excision, and three patients were treated with systemic therapy. None of the patients were treated with adjuvant radiotherapy. One patient was treated with palliative chemotherapy, one patient was treated with resection plus adjuvant chemotherapy, and one patient with neoadjuvant chemotherapy plus resection.

TABLE 1.

Clinical features of 26 identified case reports of primary cutaneous myoepithelial carcinoma.

Age‐sex	Location	Size (cm)	Initial metastasis	Treatment	Follow‐up duration (months)	New metastases
14‐F [9]	Great toe	2	NR	Amputation	NR	NR
70‐F [1]	Cheek	1	—	Excision	24	—
79‐M [1]	Retroauricular region	0.7	—	Excision	24	—
21d‐F [10]	Abdomen	NR	—	Excision	NR	NR
76‐M [11]	Plantar foot	NR	NR	Excision	NR	NR
62‐F [12]	Back	7	—	Excision	15	+
13‐F [13]	Parietotemporal scalp	NR	+	Excision + SLNB	NR	NR
NR‐NR [14]	NR	NR	NR	NR	NR	NR
9‐M [15]	Great toe	1.3	—	Amputation	20	—
51‐F [16]	Femoral region	1	—	Excision	20	—
70‐M [17]	Left buttock	6	LN+	Excision	8	—
80‐M [18]	Scalp	2	—	Excision	18	—
85‐F [19]	R shoulder	8	LN+	Excision	3	+
47‐M [20]	Scalp	6	+	Chemo	5	NR
65‐F [21]	Left ankle	NR	—	Excision	10	LR
39‐F [3]	R groin	NR	—	Excision	60	NR
59‐F [3]	L groin	NR	—	Excision	3	+
59‐M [22]	Scalp	4	+	Biopsy + palliation	NR	NR
84‐M [23]	Scalp	2.2	—	Excision	5	+
46‐F [24]	R hip	5	LN+	Excision	NR	NR
58‐F [24]	R thigh	3	—	Excision	NR	NR
64‐M [25]	Left thigh	20	LN+	Neoadjuvant chemo + resection	24	—
44‐M [26]	Left axilla	3	LN+	Excision and chemo	NR	—
26‐M [27]	R medial great toe	3	NR	Excision	24	—
34‐M [27]	Foot	1.5	NR	Excision	132	LR
30‐F [27]	Volar wrist	5	NR	Excision	96	+

Abbreviations: LN, lymph node; LR, Local recurrence; NR, not reported.

Most cases had a pan‐cytokeratin stain performed (pan‐cytokeratin, cytokeratin AE1/AE3 or some other variation of a broad‐spectrum keratin immunohistochemical stain) which was positive except in two cases, one of which demonstrated < 5% reactivity with PAN‐K, and 0% reactivity with AE1/AE3 (Table 2). Interestingly, there was considerable variation in the other immunohistochemical stains performed. Calponin, S100 and p63 showed variable positive and negative staining for those tumors for which they were tested. In the cases for which it was tested, Desmin and melanocytic markers were universally negative.

TABLE 2.

Immunohistochemical profile of 26 identified case reports of primary cutaneous myoepithelial carcinoma.

Age‐Sex	Positive	Negative
14‐F [9]	PAN‐K (< 5% reactive), CK 8/18, EMA, GFAP, Calponin, SMA	AE1/AE3, CK14, S100, Desmin, p63
70‐F [1]	Vimentin, pan‐cytokeratin, EMA, α‐SMA, Calponin	S100, GFAP, Desmin
79‐M [1]	Vimentin, pan‐cytokeratin, and α‐SMA, S100, Calponin	Desmin, GFAP
21d‐F [10]	S100, calponin, AE1/AE3, EMA	CD31, CD30, CD45, CD20, CD34, CK20, MART‐1/HMB45, Desmin SMA
76‐M [11]	AE1/AE3, Vimentin, S100	SMA, CK14, EMA, HMB45, Melan‐A
62‐F [12]	EMA, pan‐cytokeratin, CK14, 34beta‐E12, Vimentin, p63, α‐SMA, S100, GFAP	CK7, Calponin, CEA
13‐F [13]	Pan‐cytokeratin, Calponin, SMA, S100	NR
NR‐NR [14]	Pan‐cytokeratin, SMA, p63, S100	NR
9‐M [15]	Calponin	NR
51‐F [16]	Pan‐cytokeratin, EMA, Vimentin, α‐SMA, MSA, S100	Desmin, CD34, HMB45
70‐M [17]	34betae12, EMA, Vimentin, α‐SMA, p63, S100	Cytokeratin, CEA, MSA, Desmin, GFAP
80‐M [18]	KL‐1, CK 5/6, CK7, vimentin, SMA
85‐F [19]	CK7, S100, Calponin, H‐caldesmon, SMA, α‐SMA, p63, CK5/6, INI1, NSE, CD56	34BE12, CK20, GCDFP15, HHF35, HMB45, Synaptophysin, Chromogranin, CD34
47‐M [20]	AE1/AE3, S100, p63,	Calponin, Desmin, Melan‐A, CK7, Brachyury
65‐F [21]	EMA, S100, KBA62	CD34, CD45, CD56, Mart‐1, HMB45, CK20, Chromogranin, Synaptophysin, Desmin, p63, pan‐cytokeratin
39‐F [3]	Vimentin, CK7, AE1/AE3, EMA, α‐SMA, S100, ER	CK20, GFAP, BAF47 (SMARCB1)
59‐F [3]	AE1/AE3, EMA, α‐SMA, S100, GFAP	BAF47 (SMARCB1)
59‐M [22]	AE1/A23, S100, α‐SMA	p63, CEA
84‐M [23]	S100, AE1/3, MNF, CK5, P63, GFAP, SMA	NR
46‐F [24]	p63, S100, pan‐cytokeratin	HMB45, CD34
58‐F [24]	Pan‐cytokeratin, S100	p63
64‐M [25]	Calponin, α‐SMA, HHF‐35, PLAG1	NR
44‐M [26]	Pan‐cytokeratin, SMA	NR
26‐M [27]	S100, SOX10, AE1/AE3, CK5/6, CK7, PLAG1	GFAP, CK20, p63, p40, Desmin
34‐M [27]	S100, AE1/3, CK7, SMA	CK20, EMA, p63, Desmin
30‐F [27]	S100, AE1/AE3, EMA, Desmin, SMA	NR

Abbreviation: NR, not reported.

A BRAF V600E mutation was reported in one case of primary cutaneous myoepithelial carcinoma and DNA sequencing data was reported in a recent paper [21, 26]. RNA fusion data was not available for any of the cases included in our literature review. An “atypical myoepithelial neoplasm” with an EWSR1::NR4A3 fusion which did not meet the inclusion criteria for our literature review as it did not meet diagnostic criteria for a myoepithelial carcinoma has been previously reported [28]. Otherwise, we are not aware of any other primary cutaneous myoepithelial carcinomas with published DNA mutations or RNA fusions.

4. Discussion

Myoepithelial carcinoma arises from myoepithelial cells which are commonly found in the salivary glands, the breast, and the dermis. The WHO Blue Book outlines the diagnostic criteria for myoepithelial neoplasms arising in the soft tissue as morphologically, displaying a wide variety of permutations including epithelioid to spindled appearance [2]. Myoepithelial neoplasms in the soft tissue are classified as being of “uncertain differentiation” as it is unclear whether these tumors truly arise from resident myoepithelial cells. The myoepithelial “carcinoma” designation is reserved for tumors with significant mitotic activity and nuclear atypia. Immunohistochemically, keratin markers such as pan‐cytokeratin and myogenic markers including calponin, MSA, GFAP and p63 can help support the diagnosis of myoepithelial carcinoma in soft tissue. If the diagnosis is still in question, molecular testing for EWSR1 and PLAG1 rearrangements has been reported in a large proportion of tumors found outside of the salivary glands [5, 8].

Primary myoepithelial carcinoma arising from the skin is a rare entity. As per our literature review, there are fewer than 30 cases reported. The morphological and immunohistochemical features are concordant with myoepithelial neoplasms described in the soft tissue. Reported sites for this tumor include the back, the head, groin and lower extremities. This tumor has a reportedly high rate of local recurrence and metastasis and close clinical follow‐up is usually recommended [3]. To date, no guideline for systemic therapy is available; however we included case reports whereby chemotherapy was used to treat patients with advanced disease including paclitaxel, cisplatin, carboplatin, cytarabine and aclarubicin [25, 26].

To the best of our knowledge, this is the first published case of a TRPS1::PLAG1 RNA fusion identified in a primary cutaneous myoepithelial carcinoma. In the cutaneous setting, TRPS1::PLAG1 fusions are known to occur in mixed neoplasms with ductal differentiation [8]. TRPS1::PLAG1 fusions have also been previously associated with adnexal carcinomas, uterine leiomyosarcomas and myoepithelial neoplasms [6, 7, 8].

PLAG1 encodes a zinc finger nuclear transcription factor that binds to the promoter region of the insulin‐like growth factor II (IGF2) gene located on the short arm of chromosome 11 [29]. Fusion events involving PLAG1 often lead to its overexpression, by co‐opting the promoter region of its fusion partner, which may in turn upregulate IGF2 transcription [7]. IGF2 is a tightly regulated growth factor critical for normal embryonic development, particularly in cell growth and differentiation. However, when overexpressed or dysregulated, IGF2 can activate IGF‐1 receptors, triggering downstream signaling pathways with anti‐apoptotic and mitogenic effects [30]. These effects promote cellular proliferation and survival, contributing to tumorigenesis.

The immunohistochemical profile of our case, including positivity for S100, p63 and pan‐keratin and negativity for CK20 and melanocytic markers, is in accordance with previously published data on the key diagnostic features of primary cutaneous myoepithelial carcinoma. Given the relatively low number of available cases in the literature regarding the RNA fusion events and markers associated with primary cutaneous myoepithelial carcinoma, this represents a potential avenue for further research in comparing this entity with its salivary and primary soft tissue counterparts.

Author Contributions

T.G. prepared the first draft of the manuscript, obtained scanned images of the primary cutaneous myoepithelial carcinoma case report slides and performed the initial literature review. J.H. and F.J. were involved clinically in the case and provided editorial support throughout the preparation of the manuscript.

Consent

Informed, written consent was obtained from the patient for publication of this manuscript, and all efforts have been made to anonymize any personal identifying information.

Conflicts of Interest

The authors declare no conflicts of interest.

Gillis T., Howell J., and Jafarian F., “ TRPS1::PLAG1 Fusion in a Primary Cutaneous Myoepithelial Carcinoma: A Case Report and Literature Review,” Journal of Cutaneous Pathology 53, no. 2 (2026): 169–174, 10.1111/cup.70010.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.