Malignant melanoma arising from nevi, p53, p16, and Bcl-2: expression in benign versus malignant components

BACKGROUND: The etiology of malignant melanoma has been the subject of much study. Tumour suppressor genes p53 and p16 and the antiapoptotic, Bcl-2, are implicated in the development and progression of malignant melanoma. OBJECTIVE: To compare the expression of p53, p16, and the Bcl-2 genes in both benign and malignant components of malignant melanoma arising from pre-existing nevocellular nevi. METHODS: Twenty cases of malignant melanoma arising from pre-existing nevi were selected and studied by immunohistochemistry for the expression of p53 (D07) CDK4I/MTS-1/INK <4, which detects both wild and mutant type, p16 CDK4I/MTS-1/INK <4, and Bcl-2 using an avidin-biotin technique on formalin-fixed, paraffin-embedded sections. RESULTS: Fifteen cases demonstrated p53 immunoreactivity in the malignant components ranging from 5 to 20% with no expression being seen in the benign components. The p16 gene showed strong nuclear reactivity in the benign components of 14 cases and weak reaction in 6 cases; the malignant components expressed weak nuclear staining in 18 cases and cytoplasmic staining in all cases. The Bcl-2 gene was expressed strongly to moderately in benign components and weakly in malignant components of nine cases, and was negative in 11 cases. CONCLUSION: Immunostaining for p53 is expressed only in the malignant component, whereas p16 and Bcl-2 showed decreased staining and a different pattern in malignant compared with benign components. These findings suggest that expression and alterations in the subcellular localization of the cell cycle regulators may contribute to the mechanism of tumourigenesis.     

p53 expression in two cases of spiradenocarcinomas

p53 protein is a nuclear 53-kDa phosphoprotein that acts as a suppressor protein. There are several studies on the expression of p53 in skin tumors, but few deal with adnexal malignant tumors because of their rarity. We performed immunohistochemistry for the detection of p53 and Ki-67 in two cases of malignant spiradenomas and six cases of spiradenomas retrieved from our files. In our cases, p53 was expressed only in the malignant areas of the lesions, whereas the benign areas of the spiradenocarcinomas and all the spiradenomas were negative (nuclear positivity <10%). These results seem to support the idea that p53 is implicated in the malignant transformation of adnexal tumors.     

Basaloid/follicular hyperplasia overlying connective tissue/mesenchymal hamartomas simulating basal cell carcinomas

BACKGROUND: Basaloid hyperplasia has been described overlying dermatofibromas as well as in the epidermis overlying nevus sebaceus. Although the morphology of these areas may resemble that of basal cell carcinoma (BCC), in the majority of cases aggressive behavior of the proliferation is not seen. In fact, the basaloid proliferation often shows follicular differentiation and may be stimulated and maintained by its relationship with the underlying stromal cells. OBJECTIVE: We wanted to determine whether immunohistochemical staining for antibodies, which may suggest differences in pathogenesis, were different in basaloid hyperplasia overlying connective tissue/mesenchymal hamartomas and BCC. METHODS: We report 3 cases of connective tissue/mesenchymal hamartomas with overlying basaloid hyperplasia, in which the areas of the basaloid proliferation showed follicular differentiation. Immunohistochemical stains included Ber-EP4, PCNA, Ki-67, Bcl-2, p53, SM-Actin, CD31, factor XIIIa, KP-1, and CD34. RESULTS: There was a diffuse positive reaction for Ber-EP4 in all specimens and there was increased nuclear staining for PCNA and Ki-67. There was focal cytoplasmic staining for Bcl-2 in the areas of basaloid hyperplasia. Immunohistochemical staining for p53 showed only scattered positive cells except in a small focus in the areas of basaloid hyperplasia. The connective tissue component of all lesions showed diffuse staining for CD34 surrounding areas of basaloid hyperplasia in the mesenchymal component as well as in abundant S-100(+) nerves. CONCLUSION: The areas of basaloid hyperplasia in these hamartomas exhibited an immature phenotype similar to that seen in both BCCs and follicular tumors; however, the patterns of proliferation markers, p53, Bcl-2, and the surrounding stromal cell markers were similar to those of benign follicular tumors. Thus the staining pattern for this group of antibodies suggests that areas of basaloid hyperplasia are not BCC.     

Hidradenocarcinoma showing prominent mucinous and squamous differentiation and associated pagetoid cells

Herein, we report a 63‐year‐old man presenting with hidradenocarcinoma showing prominent mucinous and squamous differentiation on his back. The tumor was dermal‐based, solid and cystic. Tumor cells with squamous differentiation and with keratin pearl formation were identified predominantly in the superficial dermis, and mucinous cells were identified principally in the cystic lesion in the deep dermis. Interestingly, the additional feature of pagetoid cells was identified in the overlying epidermis. Both the mucinous cells in hidradenocarcinoma and pagetoid cells had intracytoplasmic mucin; however, they had different histopathologic findings and immunophenotypes. Mucinous cells in hidradenocarcinoma had small nuclei and abundant intracytoplasmic mucin presenting goblet cells with low rate of positive immunostaining for p53 and Ki67. In contrast, pagetoid cells had larger nuclei with less intracytoplasmic mucin. Both p53‐ and Ki67‐positive cells were increased in pagetoid cells. Additionally, mucinous cells in hidradenocarcinoma were MUC1(+)/MUC2(?)/MUC5AC(+)/MUC6(+), but pagetoid cells were MUC1(+; focal)/MUC2(?)/MUC5AC(?)/MUC6(+; focal). The derivation of pagetoid cells is unclear; however, the localized small region of pagetoid cells over the hidradenocarcinoma in the present case may suggest a common histogenesis of these two malignant neoplasms.     

Low-grade trichoblastic carcinosarcoma of the skin

We present an unusual case of cutaneous carcinosarcoma with the epithelial component closely resembling nodular basal cell carcinoma, and the mesenchymal component composed of cells constituting extended follicular papillae. A solitary tumor was excised in an 80-year-old man. Histologic sections revealed an ulcerated, asymmetric, poorly circumscribed neoplasm composed of epithelial cells arranged in lobules with peripheral palisading or in a cribriform pattern. The epithelial cells were darkly basophilic with scant cytoplasm and round or oval nuclei with an indistinct chromatin pattern and nucleoli. Nuclei crowding and mitotic figures were observed. Some lobules contained melanin. There were no shadow cells, sebaceous or apocrine glandular differentiation. Each epithelial nodule was surrounded by multiple rows of cells with pale vesicular nuclei and scant cytoplasm. Smaller epithelial aggregations were encircled by these cells concentrically; in larger ones these cells were aligned across a broad front resembling so-called "continuous papillae". Additionally, numerous small follicular germ-like structures associated with papillae were seen. The cells composing "continuous papillae" showed nuclear pleomorphism, numerous mitotic figures including atypical ones, and nuclear crowding. At foci, the transition from the multilayered arrangement of these cells into their diffuse proliferation in the stroma was seen. There were no transitions between the epithelial and stromal component; both were intermingled as though being mutually dependent, with no areas revealing a high-grade tumor or dedifferentiation. Immunohistochemically, the epithelial cell component stained with cytokeratins. The cells of the mesenchymal component tested positive for vimentin and negative for desmin and cytokeratins. The proliferation index (Ki-67) was high in both components. There were also a high number of p53-positive cells in both compartments. We propose the term "low-grade trichoblastic carcinosarcoma" for this neoplasm. We are not aware of a similar tumor published in the English literature.     

Malignant eccrine spiradenoma (spiradenocarcinoma): a clinicopathologic study of 12 cases

Malignant eccrine spiradenoma is a very rare tumor. The clinicopathologic features of 12 cases are reported herein. Six patients were men, six were women, and the average patient age was 62 years. Seven tumors were located on the trunk, three on the extremities, and two in the head and neck region. All tumors were large (average size-7.5 cm). Lesions had been present from 7 months to 30 years before surgical removal. In all cases, continuity between benign eccrine spiradenoma and areas with malignant change was observed. Malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, and hyperchromasia, loss of nested and trabecular growth patterns, and absence of a dual cell population. In most cases (8 of 12), the malignant component comprised the bulk of the lesion. Two distinctive histologic patterns were observed. Five of 12 tumors exhibited abrupt transition between a benign eccrine spiradenoma and a high-grade carcinoma component. The others lacked a clear-cut transition between benign and malignant components and were diagnostically challenging. Diagnosis in such cases was established based on the loss of two cell populations, increased nuclear to cytoplasmic ratio, hyperchromasia, and marked mitotic activity. Two tumors showed focal squamous differentiation. Five of seven patients on whom there was follow-up information were free of disease (average duration of follow-up = 3.4 years). One patient developed metastases to local lymph nodes 5 years after the primary tumor was resected. This patient had no evidence of disease 16 months after resection of her lymph node metastases.     

Sebaceous carcinoma within rippled/carcinoid pattern sebaceoma

Although the histogenesis of sebaceous carcinomas remains unclear, the occurrence of intraepidermal or intraepithelial sebaceous carcinoma in the epidermis or conjunctiva may suggest de novo histogenesis. This report describes a case of sebaceous carcinoma within preexisting rippled/carcinoid pattern sebaceoma. This lesion was composed of two (benign and malignant) components, and the benign component of the lesion showed the typical features of a rippled/carcinoid pattern sebaceoma. Although evidence of trauma as well as a vertical orientation was seen in this lesion, the malignant component of the lesion showed histopathological evidence of malignancy (sebaceous carcinoma), such as the aggregations with irregular and infiltrated borders, a sheet‐like growth pattern, and the cytopathological findings of the neoplastic cells, showing a high‐grade of malignancy (a high mitotic index and abnormal mitotic figures). The immunohistochemical staining for p53, Ki‐67 and D2‐40 also favored this diagnosis. This sebaceous carcinoma component was considered to be the incipient stage of carcinoma within preexisting sebaceoma, therefore, it was still considered to be a vertically oriented lesion. This case shows the possibility that abnormal (malignant) sebaceous germinative cells may originate within a sebaceoma, thereby suggesting that some sebaceous carcinomas may develop from preexisting sebaceomas.     

The etiology of malignant melanoma

The etiology of malignant melanoma has been intensely studied over the last decade. Much of the recent work focuses on oncongenes and tumour suppressor genes and the role of apoptosis in melanoma. Loss of tumour suppressor proteins such as p16 has been documented in melanoma and correlates with tumour progression. Mutations in the tumour suppressor p53 have also been documented in melanoma. The proto-oncongene Bcl-2 encodes a protein that inhibits apoptosis. Bcl-2 is found in normal melanocytes and benign nevi. However, lower levels are seen in melanoma. To investigate the relationship between melanoma and nevi, in our Basic and Clinical Science section, Dr. Radhi examines the expression of p53, p16, and Bcl in malignant melanoma arriving in benign nevi. P53 immunoreactivity was found only in the malignant component, with no expression being seen in the benign components of the lesion. This suggests that this tumour suppressor gene is involved in the pathogenesis of melanoma.     

Malignant peripheral nerve sheath tumor with perineurial differentiation: "malignant perineurioma"

BACKGROUND: Although benign tumors derived from the nerve sheath perineurial cell have been described from a variety of anatomic sites and are known to be a component of a number of benign neoplasms, malignant nerve sheath tumors of perineurial origin are exceedingly uncommon. METHODS: We report an unusual case of a 70-year-old male who presented with a rapidly growing mass of the left arm, subsequently shown to be a malignant nerve sheath tumor with perineurial differentiation. A brief microscopic differential diagnosis and review of the literature are discussed. RESULTS: Histologic sections show a partially circumscribed tumor of atypical spindle cells arranged in sweeping fascicles embedded in a myxoid matrix with focal whorling. Nuclear pleomorphism was evident among scattered typical and atypical mitotic figures (mean mitotic index of 7/10 high-power fields). The immunophenotypic profile consisted of only vimentin and epithelial membrane antigen (EMA) positivity, while antibodies to S-100, CD34, smooth muscle actin, and pankeratins were negative. Ultrastructural features included spindle cells with long cytoplasmic processes invested by interrupted basal lamina and pinocytotic vesicles, consistent with perineurial differentiation. CONCLUSIONS: While the histogenic source of the benign perineurioma, the perineurial cell has only rarely been described in conjunction with malignant tumors. All cases to date have shown EMA-positive and S-100-negative atypical spindled cells arranged in fascicles embedded in a myxoid matrix. In addition to immunohistochemistry, ultrastructural examination may be necessary to support the diagnosis. The diagnostic differential includes melanoma, spindle cell squamous cell carcinoma, atypical fibroxanthoma, leiomyosarcoma, and conventional malignant peripheral nerve sheath tumor, most commonly of Schwannian differentiation. Recognizing perineurial differentiation is important since few cases have been reported to date and the biological potential of these neoplasms is not known.     

p53 immunoreactivity in human malignant melanoma and dysplastic naevi

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wildtype p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P<0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P=0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.     

Expressions of p53, cyclinD1 and histopathological features in basal cell carcinomas

Background: We planned this study to analyze probable associations between p53, cyclinD1, Ki67 and histopathological features in basal cell carcinomas (BCC).
Methods: Histological differentiation types, histological growth patterns and tissue responses were analyzed in 50 cases of BCC. In immunohistochemical analysis, p53, cyclinD1 and Ki67 antibodies were investigated. P53 expression was evaluated based on a cut-off value of 25% positivity. CyclinD1 expression was graded from 0 to 3+ according to the percentage of positive nuclear staining. The percentage of positively staining cells for Ki67 was recorded.
Results: The following significant correlations were detected. Solid infiltrative type differentiation was related to the infiltrative histological growth pattern. The rates of p53 positivity and severe fibrosis in the groups of mixed and infiltrative growth patterns were higher than others. Besides, p53-positive cases showed more severe fibrosis and had a higher mean value for Ki67 index. Epidermal p53 and cyclinD1 clones in normal epidermal areas adjacent to tumors were noticed in 42% and 52% of the cases, respectively.
Conclusions: P53 expression seems to be related to Ki67 index and some histopathological features of BCC, such as infiltrative histological growth pattern and probably fibrosis.     

High‐grade trichoblastic carcinoma arising through malignant transformation of trichoblastoma: Immunohistochemical analysis and the expression of p53 and phosphorylated AKT

Trichoblastoma (TB) is a benign cutaneous adnexal neoplasm. The lesion typically presents as a slow‐growing, solitary, well‐circumscribed nodule measuring up to 3 cm in diameter. On rare occasions, TB causes malignant transformation into an aggressive form described as high‐grade trichoblastic carcinoma. Four such cases have been reported to date; all were described as high‐grade trichoblastic carcinomas. Here, we describe the case of a 72‐year‐old Japanese male patient with a rapidly enlarging subcutaneous tumor on his lower back, which was diagnosed as high‐grade trichoblastic carcinoma. Histopathologically, the tumor featured both benign and malignant components, and a transition zone between these states was clearly evident. In the immunohistochemical analysis, a malignant component was positive for p53 and showed stronger staining of phospho‐RAC‐α serine/threonine‐protein kinase (AKT) Ser473 in comparison with a benign component. These results suggest that loss of p53 function and activation of phosphatidylinositol 3‐kinase–AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.     

Sebaceous carcinoma with apocrine differentiation

A 54-year-old male had a dome-shaped and skin-colored nodule on his nose. Histopathologically, we diagnosed this neoplasm as a low-grade sebaceous carcinoma rather than a sebaceoma based on the scanning magnification and cytology. This low-grade sebaceous carcinoma was associated with glandular structures. We regarded the glandular structures as those of apocrine glandular differentiation based on 1) the histopathologic features of the glandular structures formed by columnar luminal cells with evidence of decapitation secretion; 2) the expression of cytokeratin (CK) 19, CK8, CK8/18, and CK7 in the luminal cells; 3) the positive reaction of carcinoembryonic antigen and epithelial membrane antigen on the luminal surface and in the cytoplasm of the luminal cells; and 4) the common embryologic origin of the folliculosebaceous-apocrine unit. We found CK15 expression in undifferentiated cells within the mantles of normal hair follicles, suggesting that sebaceous stem cells might exist in mantles as follicular stem cells exist in bulge areas. Pluripotent stem cells in the folliculosebaceous-apocrine unit can give rise to follicular stem cells, sebaceous stem cells, and apocrine stem cells. Our patient's neoplasm showed apocrine glandular differentiation and partial immunohistochemical positivity for CK15 in the neoplastic aggregations. We believe this neoplasm originated from pluripotent stem cells destined to become sebaceous stem cells or from sebaceous stem cells, which also have the ability to differentiate within apocrine glands.     

p53 protein expression in cutaneous T-cell lymphomas

p53 is an oncosuppressor gene located on chromosome 17p. Point mutations of the p53 gene are seen frequently in human malignancies, and are closely associated with malignant transformation under in vitro conditions. Mutated p53 protein shows a slow cell turnover rate, and accumulates in cells at the nuclear and/or cytoplasmic level. As a result, mutated p53 protein can be detected more readily by immunohistology than the wild-type protein. In this study, we used a monoclonal anti-p53 antibody (clone D07) to examine the expression of p53 protein in 25 cutaneous T-cell lymphomas (CTCL) of low- and high-grade malignancy, i.e. mycosis fungoides (n = 6), Sézary's syndrome (n = 2), and large cell lymphomas of pleomorphic (n = 14) or anaplastic (n= 3) subtype. The results showed that easily detectable p53 protein was present in many of the neoplastic cells in half of the high-grade lymphomas. In contrast, in the low-grade lymphomas no, or only very few, p53-positive neoplastic cells could be detected. These findings suggest that molecular and/or genetic alterations of p53 may be implicated in the pathogenesis of high-grade CTCL, but are unlikely to be of critical importance in low-grade CTCL.     

Syringocystadenocarcinoma Papilliferum in Situ: A Case Report and Review of the Literature

Syringocystadenocarcinoma papilliferum is an exceedingly rare malignant neoplasm of the apocrine glands. There are only about half a dozen cases reported in the literature with one case being an in situ lesion. A 32‐year‐old Nigerian female presented with a 1‐cm, hyperpigmented, slow‐growing verrucous nodule located on her mid‐posterior neck. The lesion had been present since birth. Histopathological examination revealed bilocular cystic cavities with papillary projections lined by double layers of epithelium. The luminal layer was composed of columnar cells with decapitation‐type secretion. The fibrovascular stroma within the papillary projections contains numerous plasma cells with some lymphoid cells. The cystic cavities showed close apposition to the epidermis of the skin with focal, keratinizing squamous epithelium lining that was contiguous to the infundibular epithelium in foci. Necrosis en masse was present within the tumor. There were focal areas of solid aggregates of tumor cells with crowded, pleomorphic, and hyperchromatic nuclei. Many mitoses, some of them atypical, were identified. The tumor was confined within the cystic cavities with no dermal invasion. A diagnosis of syringocystadenocarcinoma papilliferum in situ was made.     

Syringomatous carcinoma in a young patient treated with Mohs micrographic surgery

Syringomatous carcinoma (SC) has typically been observed in middle-aged and older patients. We report a case of SC mimicking an epidermoid cyst in a 23-year-old Asian man. Histopathologic examination results showed a dermal neoplasm consisting of nests of basaloid cells, focal areas of ductal differentiation, moderate dermal fibrosis, and moderate nuclear atypia consistent with a diagnosis of SC. No perineural involvement was noted. Results of 2005. immunohistochemical analysis revealed positivity for high- and low-molecular-weight cytokeratins, as well as for carcinoembryonic antigen (CEA). There was scattered immunoreactivity to S-100 protein. The tumor was completely excised Pennsylvania. using Mohs micrographic surgery (MS). This case demonstrates the importance of differentiating SC from other benign or malignant entities, the value of a prompt diagnosis of SC, and the effective treatment of SC with MMS.     

Low-grade adnexal carcinoma of the skin with multidirectional (glandular, trichoblastomatous, spiradenocylindromatous) differentiation

The conjoint occurrence of follicular, sebaceous, or apocrine differentiations in a cutaneous adnexal neoplasm is a known event, more often encountered in benign neoplasms, whereas reports of cutaneous malignant adnexal tumors with bilineage or trilineage differentiation are few. A new case of a cutaneous malignant adnexal neoplasm with multidirectional differentiation is reported here. A 57-year-old woman presented with a long-standing, slowly growing, asymptomatic solitary tumor the size of a large nut in the coccygeal area, which was surgically excised. Ten years after the surgery, there was no evidence of recurrence or metastasis. Microscopically, the neoplasm was located in the dermis with focal extension into the subcutis. It was asymmetric, horizontally oriented, and mostly composed of small nodules that varied in shape from round and oval aggregations to elongated strands and irregular islands; the nodules were either clustered, formed a jigsaw puzzle-like pattern or were dispersed. The nodules were composed of small basaloid cells sometimes intermixed with larger cells with ample cytoplasm forming glandular structures. Rare nodules resembled elements seen in a spiradenoma by containing scattered lymphocytes and globules of hyalinized eosinophilic basal membrane material. The stroma was paucicellular, but focally it resembled that seen in perifollicular mesenchyme. Mitotic figures, including abnormal ones, were infrequent, but mild nuclear pleomorphism, nuclear crowding, and individual cell necrosis were easily appreciable in both small basaloid cells and cells with clear cytoplasm. Perineural invasion was apparent. We classified this tumor as a well-differentiated adnexal carcinoma demonstrating combined follicular and apocrine differentiation. It differs from previously published cases of malignant adnexal tumors with multidirectional differentiation and further exemplifies the spectrum of diversity encountered in malignant proliferations with differentiation toward the folliculosebaceous-apocrine unit.     

Biphasic sarcomatoid basal cell carcinoma (carcinosarcoma): four cases with immunohistochemistry and review of the literature

BACKGROUND: Biphasic sarcomatoid carcinoma (BSC), or carcinosarcoma, is an uncommon biphasic neoplasm that has been reported in diverse anatomical sites. The tumor is composed of a malignant epithelial component intimately associated with a malignant mesenchymal component, which may be homologous or heterologous. Twenty-three cases of primary cutaneous BSC have been reported in the English literature. In only eight of these cases was basal cell carcinoma the epithelial component. METHODS: We report a further four cases of primary cutaneous biphasic basal cell carcinoma, and include the clinical, histological and immunohistochemical features. RESULTS: The four cases showed basal cell carcinoma associated with a pleomorphic sarcomatous stroma. In addition, myofibroblastic differentiation and foci of osteoid were present in one case, and leiomyosarcomatous areas in another. The epithelial components were positive for several epithelial markers. The mesenchymal components were positive for vimentin and CD99, and negative for epithelial markers. p53 was positive with equal intensity in both epithelial and mesenchymal components. A significantly worse outcome was observed in patients with tumors measuring 40 mm or more at excision. CONCLUSIONS: The sarcomatous component of the tumor is best regarded as a metaplastic transformation of the carcinomatous component. These tumors are potentially aggressive if incompletely excised, and complete resection is recommended.     

Cutaneous composite hemangioendothelioma with satellitosis and lymph node metastases

The term hemangioendothelioma has been used in recent years to name a heterogeneous group of vascular neoplasms, intermediate in both biological behavior and histopathologic appearance between benign tumors (hemangiomas) and frankly malignant tumors (angiosarcomas). Thus, within the spectrum of hemangioendothelioma have been successively included epithelioid hemangioendothelioma, spindle cell hemangioendothelioma, retiform hemangioendothelioma, kaposiform hemangioendothelioma, polymorphous hemagioendothelioma of the lymph nodes, papillary intralymphatic angioendothelioma (PILA) and composite hemangioendothelioma. The latter is a vascular neoplasm showing varying combinations of benign, low-grade malignant and malignant vascular components. We herein report a case of composite hemangioendothelioma showing a combination of retiform hemangioendothelioma, epithelioid hemangioendothelioma, spindle cell hemangioma and PILA. The neoplasm showed a more aggressive behavior than other reported cases of composite hemangioendothelioma and it developed satellitosis and metastases to the inguinal lymph nodes. Neoplastic cells expressed immunoreactivity for Prox-1, supporting a lymphatic line of differentiation.