Primary cutaneous carcinosarcoma: report of a case with poroid and fibrohistiocytic differentiation

El carcinosarcoma primario cutáneo es un tumor infrecuente de la piel y corresponde a una neoplasia bifásica compuesta por un componente epitelial y otro mesenquimático, ambos con características de malignidad, de causa incierta. El componente epitelial frecuentemente presenta diferenciación escamoide o basaloide, pero puede adquirir otra diferenciación como anexial. El componente mesenquimático puede presentar diferenciación variada, como por ejemplo muscular lisa, nerviosa, osteoblástica, condroblástica, miofibroblastica, angiomatosa, fibrosarcomatosa entre otras. Se ha reportado que tiene recurrencia local con bajo potencial metastásico. Presentamos el caso de un paciente hombre de 89 años, con un tumor exofítico en la parte posterior de la pierna izquierda, cuyo examen histopatológico mostró un Carcinosarcoma cutáneo, con diferenciación anexial (porocarcinoma) y de Sarcoma pleomórfico con diferenciación fibrohistiocitaria.


Correspondent
author: Natalia Gómez Allende Email: negomez@uc.cl C arcinosarcoma is a biphasic neoplasm composed of malignant epithelial and mesenchymal elements that are intimately admixed 1 . It has been described in many different organs such as the uterus, bladder, lung, kidney, breast, oropharynx, and the gastrointestinal tract, but it very rarely develops in the skin 2 .The prognosis is uncertain and depends on the epithelial component, but local recurrence and metastasis rates are lower when compared to similar tumors located elsewhere in the body.

cAse RepoRt
An 89-year-old man presented with an ulcerated solitary exophytic nodule located on the back of the left leg that had steadily grown over the past year to a diameter of 2.6 cm. It was ulcerated and bled occasionally but lymph nodes were unaffected. An excisional biopsy and skin graft were performed, and no residual tumor was detected (figure1).
The pathologic findings showed an ulcerated invasive biphasic mass with a mesenchymal component formed by large irregular dyscohesive pleomorphic mono and multinucleated cells with wide eosinophilic cytoplasm, and some cells with eosinophilic intracytoplasmic globules. They also had irregular nuclei with vesicular and granular chromatin, and prominent nucleoli. Three atypical mitoses per high power field were identified. The epithelial component was circling its mesenchymal counterpart, and consisted of atypical cohesive cells with clear cytoplasm, round and oval-shaped nuclei with vesicular chromatin and prominent nucleoli, forming a trabecular pattern, nests, and some tubular structures ( figure 2A-2D).
Immunohistochemical staining showed a positive reaction for EMA and it was negative for CD10, CD31 and MyoD1 in the epithelial component. In the mesenchymal component, there was a positive reaction for CD10, and negative for EMA, CD31 and MyoD1 (figure 3A-3D).
The histopathological findings were consistent with a cutaneous carcinosarcoma with adnexal differentiation (porocarcinoma), and pleomorphic sarcoma with fibrohistiocytic differentiation.

Discussion
Carcinosarcoma is a malignant biphasic tumor described in different anatomical sites but infrequently develops in the skin. The first description of carcinosarcoma was made by Virchow in 1864 3 but a primary cutaneous carcinosarcoma was first described by Grime in 1948 4 in a biopsy showing squamous cell carcinoma with fibrosarcoma that had developed in a post-burn scar. Since then, we found 80 cases of cutaneous carcinosarcoma reported in the English literature (Table 1). According to these case reviews, the average age of clinic presentation is 76 years old, and ranges from 48 to 92 years old. It is more frequent in men (n: 57) than in women (n: 23), 71.2% compared to 28.7%. In the skin the most frequent locations are photoexposed areas, mainly in the face and ears although they have been described in places like the armpit and gluteus 1,2 .
The prognosis is variable and depends directly on the epithelial carcinoma component differentiation. If it comes from the epidermis (basaloid or squamous), the disease-free survival rate at 5 years is 70%. However, The epithelial component can arise from the epidermis (basaloid or squamous) or derived from eccrine, apocrine, follicular, matrical, or trichilemmal skin appendages 5  Clinically the presentation is variable and often presents as an exophytic nodular lesion that can mimic a basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, or Merkel-cell carcinoma 6 .
There are several morphological criteria that define a carcinosarcoma. First, dual neoplasia with epithelial and mesenchymal components must be confirmed by histology and immunohistochemical reactions. Second, a collision tumor or metastasis must be excluded. Lastly, cells must be coherent and show solid pattern proliferation without stromal sarcomatous changes in the surrounding tissue 7,8 .
The histogenesis of carcinosarcoma remains unknown, although four theories have been proposed [9][10][11] . First among them is the theory of collision or convergence, which posits that the tumor is composed of two different synchronic neoplasms originating from two or more undifferentiated progenitor cells. Second is the theory of conversion, in which a part of the carcinoma shows a metaplastic transformation into a sarcomatous component. Third is the theory of composition that hypothesizes that the mesenchymal component is not a tumor but reactive stroma with "pseudosarcomatous" changes. Finally there is the divergent or combination theory that both the epithelial and the mesenchymal components are originated from a common pluripotential progenitor cell 4 .
Biernat et al 10 demonstrated the similar expression of p53 in both the epithelial and sarcomatous components which supports the theory that they have a common origin, favoring the divergence or conversion theories.
The diagnosis can be made by biopsy analysis, using Hematoxylin and Eosin staining in addition to complementary immunohistochemical analyses that allows the origin of the cell line to be more accurately classified. The treatment is surgical resection by Mohs surgery with strict clinical follow up.
The differential diagnosis includes cutaneous metastasis from sarcoma, squamous cell carcinoma, melanoma, or atypical fibroxanthoma.

conclusion
We have presented the case of an 89-year-old man with an exophytic tumor histopathologically diagnosed as cutaneous carcinosarcoma with adnexal differentiation (porocarcinoma) and pleomorphic sarcoma with fibrohistiocytic differentiation. Primary cutaneous carcinosarcoma is an infrequent neoplasm of uncertain etiology, potentially locally recurrent and metastatic. The prognosis is primarily determined by the epithelial component (adnexal or epidermic), and the elected treatment is surgical excision by Mohs surgery with strict clinical follow up.