Combined cutaneous tumors with a melanoma component: A clinical, histologic, and molecular study

Amin, Sapna M.; Cooper, Chelsea; Yélamos, Oriol; Lee, Christina Y.; Sholl, Lauren Meldi; Fouchardière, Arnaud de la; Guitart, Joan; Gerami, Pedram

doi:10.1016/j.jaad.2015.06.005

Cited by 19 publications

(22 citation statements)

References 41 publications

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“…An alternative possibility to explain the observed melanocytic differentiation is through the occurrence of melanocytic metaplasia, a process known to take place in a variety of nonmelanocytic neoplasias, with the most common being breast, 40 thyroid, 41 and skin. 42 Similarly, smooth muscle metaplasia is known to occur in normal endometrium and female breast, 43 and it has been reported in extrauterine endometriosis 44 and renal carcinoma. 45 Interestingly, it has been reported that lymph node LECs express the melanocytic specific protein tyrosinase, 46 which catalyzes the production of melanin from tyrosine by oxidation.…”

Section: Discussionmentioning

confidence: 96%

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Yue

Pacheco

Cheng

et al. 2016

The American Journal of Pathology

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Angiomyolipoma (AML) is a tumor closely related to lymphangioleiomyomatosis (LAM). Both entities are characterized by the proliferation of smooth muscle actin and melanocytic glycoprotein 100 (recognized by antibody HMB-45)epositive spindle-shaped and epithelioid cells. AML and LAM are etiologically linked to mutations in the tsc2 and tsc1 genes in the case of LAM. These genes encode the proteins tuberous sclerosis complex (TSC)-1 and TSC2, which are directly involved in suppressing the mechanistic target of rapamycin cell growth signaling pathway. Although significant progress has been made in characterizing and pharmacologically slowing the progression of AML and LAM with rapamycin, our understanding of their pathogenesis lacks an identified cell of origin. We used an AML-derived cell line to determine whether TSC2 restitution brings about the cell type from which AML arises. We found that AML cells express lymphatic endothelial cell markers consistent with lymphatic endothelial cell precursors in vivo and in vitro. Moreover, on TSC2 correction, AML cells mature into adult lymphatic endothelial cells and have functional attributes characteristic of this cell lineage, suggesting a lymphatic endothelial cell of origin for AML. These effects are dependent on TSC2-mediated mechanistic target of rapamycin inactivation. Finally, we demonstrate the in vitro effectiveness of norcantharidin, a lymphangiogenesis inhibitor, as a potential co-adjuvant therapy in the treatment of AML. (Am J Pathol 2016 http://dx

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Section: Discussionmentioning

confidence: 96%

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Yue

Pacheco

Cheng

et al. 2016

The American Journal of Pathology

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“…Collision tumors are defined as two neoplasms composed of different cell origins that present in close proximity but maintain a well‐defined boundary . Combined tumors are defined as neoplasms composed of two phenotypically distinct yet intermingled cell populations, for which the use of immunohistochemical studies is usually required to highlight the two distinct cell populations . Overlap between these tumors may occur in which tumors show a mixed pattern that can fall into both collision and combined categories .…”

Section: Discussionmentioning

confidence: 99%

“…Colonized tumors develop when one type of tumor cell population permeates but remains within a second tumor . Lastly, biphenotypic tumors are defined as tumors that develop from single precursor tumor cells that have undergone dual differentiation, in which, the individual tumor cells would have to exhibit dual features either immunohistochemically or ultrastructurally …”

Section: Discussionmentioning

confidence: 99%

Cutaneous neoplasms composed of melanoma and carcinoma: A rare but important diagnostic pitfall and review of the literature

et al. 2019

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We report two cases of combined cutaneous tumors composed of melanoma and carcinoma. The first tumor presented as a 5-mm pink-blue macule over the right zygomatic arch in an 85-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of melanoma (highlighted by SOX10 and MART-1, with high Ki-67 proliferative index) intermixed with nodular basal cell carcinoma (highlighted by pan-cytokeratin and Ber-EP4). The neoplastic melanocytes were confined to the basal cell carcinoma nodules, and a diagnosis of combined melanoma in situ and basal cell carcinoma was rendered. After therapeutic excision, the patient was disease-free at 9 months after the initial diagnosis. The second tumor presented as a 6-mm pink-brown crusted papule on the right forehead in an 89-yearold man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of malignant melanoma (MM) (highlighted by S100 and MART-1) intermixed with squamous cell carcinoma (SCC) (highlighted by cytokeratin and p63), and a diagnosis of combined MM-SCC was rendered. These two cases highlight the importance of recognizing these rare types of melanocytic-epithelial cutaneous neoplasms to arrive at an accurate diagnosis that may inform appropriate disease stage and therapy. K E Y W O R D Sbasal cell carcinoma, combined tumors, melanoma, squamous cell carcinoma

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“…Others such as Pierard et al considered these malignancies to be “confluent” and favored a field cancerization phenomenon in which carcinogenic environmental exposure (such ultraviolet [UV] radiation exposure) primed a field in which 2 neoplasms were likely to proliferate in one anatomic space. Still other authors postulated that these biphasic lesions develop from a common progenitor cell that was capable of undergoing dual differentiation …”

Section: Discussionmentioning

confidence: 99%

“…Amin et al examined 16 combined‐cutaneous tumors with a melanoma component (3 of which were MM‐BCC) and surmised that combined cutaneous tumors were potentially more indolent than melanomas occurring on their own, postulating that the atypical melanocytes may be dependent upon the epithelial component of the tumor to grow and invade. Alternatively, one could argue that an overestimation of depth contributed to the better than expected survival rates.…”

Section: Discussionmentioning

confidence: 99%

Colliding, colonizing or combining? Four cases illustrating the unique challenges presented by melanoma arising in conjunction with basal cell carcinoma

et al. 2018

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Biphasic lesions comprised of melanocytic and epithelial components are rare entities believed to arise either as a collision of 2 histologically distinct lesions in the same anatomic location or as a singular progenitor tumor differentiating along 2 differing lineages. Regardless of mechanism of origin, these tumors present unique challenges in pathologic interpretation and in determining appropriate measurements, which assigns subsequent prognosis to the patient. We present 4 tumors of melanoma co-existing with basal cell carcinoma (BCC) and discuss relevant literature regarding these biphasic entities. Patients consisted of 3 males and 1 female, ranging in age from 62 to 93, with lesions located on the shoulder, frontal scalp, forearm and nose. Three of 4 lesions showed melanoma cells limited to BCC tumor lobules, without evidence of direct dermal invasion by melanoma cells, raising the question of whether or not these tumors should be classified as in situ or invasive melanoma. These cases highlight the complexity that such lesions pose to dermatopathologists, in terms of their uncertain origin and variable microscopic appearance. In the absence of data regarding outcomes for these tumors (given their rarity), it is important to utilize a case-by-case approach, with careful clinical correlation and appropriate use of ancillary techniques.

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Combined cutaneous tumors with a melanoma component: A clinical, histologic, and molecular study

Cited by 19 publications

References 41 publications

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Cutaneous neoplasms composed of melanoma and carcinoma: A rare but important diagnostic pitfall and review of the literature

Colliding, colonizing or combining? Four cases illustrating the unique challenges presented by melanoma arising in conjunction with basal cell carcinoma

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