LETTERS
TO THE
EDITOR
Spitz Nevus Intermingling With Hemangioma, Angiomatoid Spitz Nevus, Angiotropism, and Vascular Co-option Viewed With Differing Availability Heuristics To the Editor: We read the article by Drs. Fernandez-Flores and Saeb-Lima1 regarding a “Spitz nevus intermingling with a hemangioma” with great interest. The authors describe a Spitz nevus on the right thigh of a 10-year-old boy intermingled with a hemangioma. The authors reference research by Wu et al suggesting that abnormalities in regulatory pathways might contribute to vascular proliferation in association with a Spitz nevus and research by Barnhill et al regarding angiotropic neonatal congenital melanocytic nevus and angiotropism in cutaneous melanoma,2–4 but dismiss the relevance of these findings to their case by stating that “more cases would be expected in the literature if either of the 2 pathogenic explanations (a common defect to the melanocytic nevus and the hemangioma on one hand and the tropism by the melanocytes to the blood vessels on the other) was right”.1 Although the authors review reports of Spitz nevi associated with vascular tumors,5–8 they do not refer recent research on vascular cooption and angiotropism in melanocytic neoplasia9 or the literature on angiomatoid Spitz nevi.10 We feel that the growing body of research regarding the relationship of melanocytic proliferations with vasculature should not be so easily dismissed. We report a recently encountered case of an angiomatoid Spitz nevus with a microvenular hemangioma-like vascular pattern as an example. Our The authors declare no conflicts of interest.
FIGURE 1. A symmetric pink papule on the anterior lower leg.
experience is that vascular proliferation is not uncommon in Spitz nevi and that recent research findings suggest a plausible explanation for this phenomenon.
CASE A 61-year-old man in excellent health was noted to have a raised papule with variable hyperpigmentation on his anterior lower leg (Fig. 1). The lesion had grown over the past few months and was excised. The clinical impression was that of a dermatofibroma and the
initial pathologist suspected a sclerosing hemangioma type of dermatofibroma but forwarded the case for consultation because of the prominent spindle-cell population noted. Review of the biopsy revealed increased numbers of spindle and epithelioid cells associated with a prominent vascular network (Figs. 2 and 3). The vascular network resembled a microvenular hemangioma but was limited to areas of melanocytic proliferation. A CD34 stain highlighted the prominent vascular network (Fig. 4) and S-100
FIGURE 2. Low-powered examination reveals a dome-shaped proliferation of spindle cells (hematoxylin and eosin stained sections; original magnification ·40).
Am J Dermatopathol Volume 0, Number 0, Month 2017
www.amjdermatopathology.com |
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
1
Letters to the Editor
Am J Dermatopathol Volume 0, Number 0, Month 2017
and Melan-A (Fig. 5) stains highlighted the melanocytic proliferation.
DISCUSSION
FIGURE 3. Closer inspection reveals proliferation of spindle cells associated with increased numbers of delicate branching vascular channels dissecting through collagen fibers (hematoxylin and eosin stained sections; original magnification ·200).
FIGURE 4. CD34 decorates the many small blood vessels associated with the melanocytic proliferation (original magnification ·200).
FIGURE 5. S-100 stain highlights the spindle-cell proliferation associated with blood vessels (original magnification ·200).
2
| www.amjdermatopathology.com
Vascular co-option of tumor cells through interactions with abluminal vascular surfaces has been suggested as a mechanism for angiotropism and pericytic mimicry.9 The vascular component in our case exhibits features of a microvenular hemangioma by demonstrating “a dermal proliferation of thin-walled, often branching vascular channels dissecting through collagen fibers”11 but is intimately associated with the melanocytic component and eosinophilic stroma. The findings are typical of an angiomatoid Spitz nevus.10 The matching and intermingling silhouettes of the 2 proliferations provide compelling circumstantial evidence that proliferation of vasculature and melanocytes may at times be related. Spitz nevi typically present as pink papules suspected of being a hemangioma. Pericytes and various stromal cells can be important contributors to melanoma development, and it is reasonable to suspect that they also may play a role in benign melanocytic neoplasia as well.12 Dismissing a hypothesis simply because “more cases would be expected in the literature if either .pathogenic explanations .was right” serves as an example of availability heuristic bias.13 We have a different bias based on familiarity with the hypotheses of cooption and extravascular migratory metastasis and the cases encountered in our referral practices. Exciting research on serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2 (SERPIN B2) immunostaining of human metastatic melanoma in brain demonstrate how melanocytes and blood vessels might interact. Heterotypic interactions of melanoma cells with tumor-associated stroma cells reveal a complex interaction of tumor with surrounding stroma.14 Reports of single cases such as ours and the report by Drs. Fernandez-Flores and SaebLima are both fraught with the possibility of heuristic bias. Angiomatoid Spitz nevi represent only a minor subset of Spitz nevi, but architectural features suggest that the vascular proliferation is likely reactive in many cases. We
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 0, Number 0, Month 2017
suspect that the observations of Drs. Fernandez-Flores and Saeb-Lima point to something more than coincidence. Thomas N. Helm, MD Klaus F. Helm, MD Department of Dermatology, Buffalo Medical Group, Williamsville, NY Mr. Klaus Helm is now with the Departments of Dermatology and Pathology, Penn State Health Hershey Medical Center, Hershey, PA
ACKNOWLEDGMENTS We thank Dr. Mazin Dhafir for generously sharing the clinical image in Figure 1 and his patient for permitting publication of the clinical photograph. REFERENCES 1. Fernandez-Flores A, Saeb-Lima M. Spitz nevus intermingling with hemangioma. Am J Dermatopathol. 2016;38:780–783.
2. Wu PA, Mancini AJ, Marghoob AA, et al. Simultaneous occurrence of infantile hemangioma and congenital melanocytic nevus: coincidence or real association? J Am Acad Dermatol. 2008;58:S16–S22. 3. Barnhill RL, Chastain MA, Jerdan MS, et al. Angiotropic neonatal congenital melanocytic nevus: how extravascular migration of melanocytes may explain the development of congenital nevi. Am J Dermatopathol. 2010;32: 495–499. 4. Barnhill R, Dy K, Lugassy C. Angiotropism in cutaneous melanoma: a prognostic factor strongly predicting risk for metastasis. J Invest Dermatol. 2002;119:705–706. 5. Hartley AH, Rasmussen JE. Hemangiomas and Spitz nevi. Pediatr Rev. 1990;11:262–267. 6. Hamm H, Hoger PH. Skin tumors in childhood. Dtsch Arztebl Int. 2011;108:347–353. 7. Arica DA, Arica IE, Yayli S, et al. Spitz nevus arising upon a congenital glomuvenous malformation. Pediatr Dermatol. 2013;30:e25–e26. 8. Zelger BG, Wambacher B, Steiner H, et al. Cutaneous epithelioid hemangioendothelioma, epithelioid cell histiocytoma and Spitz nevus. Three separate epithelioid tumors in one patient. J Cutan Pathol. 1997;24:641–647.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editor 9. Bentolila LA, Prakash R, Mihic-Probst D, et al. Imaging of angiotropism/vascular cooption in a murine model of brain melanoma: implications for melanoma progression along extravascular pathways. Sci Rep. 2016;6: 23834. 10. Tetzlaff MT, Xu X, Elder DE, et al. Angiomatoid Spitz nevus: a clinicopathological study of six cases and a review of the literature. J Cutan Pathol. 2009;36: 471–476. 11. Napekoski KM, Fernandez AP, Billings SD. Microvenular hemangioma: a clinicopathologic review of 13 cases. J Cutan Pathol. 2014;41: 816–822. 12. Trevino-Villarreal JH, Cotanche DA, Sepulveda R, et al. Host-derived pericytes and Sca-1+ cells predominate in the MART1-stroma fraction of experimentally induced melanoma. J Histochem Cytochem. 2011;59: 1060–1075. 13. Detmer DE, Fryback DG, Gassner K. Heuristics and biases in medical decision-making. J Med Educ. 1978;53:682–683. 14. Valiente M, Obenauf AC, Jin X, et al. Serpins promote cancer cell survival and vascular cooption in brain metastasis. Cell. 2014;156: 1002–1016.
www.amjdermatopathology.com |
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
3
TO THE
EDITOR
Spitz Nevus Intermingling With Hemangioma, Angiomatoid Spitz Nevus, Angiotropism, and Vascular Co-option Viewed With Differing Availability Heuristics To the Editor: We read the article by Drs. Fernandez-Flores and Saeb-Lima1 regarding a “Spitz nevus intermingling with a hemangioma” with great interest. The authors describe a Spitz nevus on the right thigh of a 10-year-old boy intermingled with a hemangioma. The authors reference research by Wu et al suggesting that abnormalities in regulatory pathways might contribute to vascular proliferation in association with a Spitz nevus and research by Barnhill et al regarding angiotropic neonatal congenital melanocytic nevus and angiotropism in cutaneous melanoma,2–4 but dismiss the relevance of these findings to their case by stating that “more cases would be expected in the literature if either of the 2 pathogenic explanations (a common defect to the melanocytic nevus and the hemangioma on one hand and the tropism by the melanocytes to the blood vessels on the other) was right”.1 Although the authors review reports of Spitz nevi associated with vascular tumors,5–8 they do not refer recent research on vascular cooption and angiotropism in melanocytic neoplasia9 or the literature on angiomatoid Spitz nevi.10 We feel that the growing body of research regarding the relationship of melanocytic proliferations with vasculature should not be so easily dismissed. We report a recently encountered case of an angiomatoid Spitz nevus with a microvenular hemangioma-like vascular pattern as an example. Our The authors declare no conflicts of interest.
FIGURE 1. A symmetric pink papule on the anterior lower leg.
experience is that vascular proliferation is not uncommon in Spitz nevi and that recent research findings suggest a plausible explanation for this phenomenon.
CASE A 61-year-old man in excellent health was noted to have a raised papule with variable hyperpigmentation on his anterior lower leg (Fig. 1). The lesion had grown over the past few months and was excised. The clinical impression was that of a dermatofibroma and the
initial pathologist suspected a sclerosing hemangioma type of dermatofibroma but forwarded the case for consultation because of the prominent spindle-cell population noted. Review of the biopsy revealed increased numbers of spindle and epithelioid cells associated with a prominent vascular network (Figs. 2 and 3). The vascular network resembled a microvenular hemangioma but was limited to areas of melanocytic proliferation. A CD34 stain highlighted the prominent vascular network (Fig. 4) and S-100
FIGURE 2. Low-powered examination reveals a dome-shaped proliferation of spindle cells (hematoxylin and eosin stained sections; original magnification ·40).
Am J Dermatopathol Volume 0, Number 0, Month 2017
www.amjdermatopathology.com |
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
1
Letters to the Editor
Am J Dermatopathol Volume 0, Number 0, Month 2017
and Melan-A (Fig. 5) stains highlighted the melanocytic proliferation.
DISCUSSION
FIGURE 3. Closer inspection reveals proliferation of spindle cells associated with increased numbers of delicate branching vascular channels dissecting through collagen fibers (hematoxylin and eosin stained sections; original magnification ·200).
FIGURE 4. CD34 decorates the many small blood vessels associated with the melanocytic proliferation (original magnification ·200).
FIGURE 5. S-100 stain highlights the spindle-cell proliferation associated with blood vessels (original magnification ·200).
2
| www.amjdermatopathology.com
Vascular co-option of tumor cells through interactions with abluminal vascular surfaces has been suggested as a mechanism for angiotropism and pericytic mimicry.9 The vascular component in our case exhibits features of a microvenular hemangioma by demonstrating “a dermal proliferation of thin-walled, often branching vascular channels dissecting through collagen fibers”11 but is intimately associated with the melanocytic component and eosinophilic stroma. The findings are typical of an angiomatoid Spitz nevus.10 The matching and intermingling silhouettes of the 2 proliferations provide compelling circumstantial evidence that proliferation of vasculature and melanocytes may at times be related. Spitz nevi typically present as pink papules suspected of being a hemangioma. Pericytes and various stromal cells can be important contributors to melanoma development, and it is reasonable to suspect that they also may play a role in benign melanocytic neoplasia as well.12 Dismissing a hypothesis simply because “more cases would be expected in the literature if either .pathogenic explanations .was right” serves as an example of availability heuristic bias.13 We have a different bias based on familiarity with the hypotheses of cooption and extravascular migratory metastasis and the cases encountered in our referral practices. Exciting research on serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2 (SERPIN B2) immunostaining of human metastatic melanoma in brain demonstrate how melanocytes and blood vessels might interact. Heterotypic interactions of melanoma cells with tumor-associated stroma cells reveal a complex interaction of tumor with surrounding stroma.14 Reports of single cases such as ours and the report by Drs. Fernandez-Flores and SaebLima are both fraught with the possibility of heuristic bias. Angiomatoid Spitz nevi represent only a minor subset of Spitz nevi, but architectural features suggest that the vascular proliferation is likely reactive in many cases. We
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 0, Number 0, Month 2017
suspect that the observations of Drs. Fernandez-Flores and Saeb-Lima point to something more than coincidence. Thomas N. Helm, MD Klaus F. Helm, MD Department of Dermatology, Buffalo Medical Group, Williamsville, NY Mr. Klaus Helm is now with the Departments of Dermatology and Pathology, Penn State Health Hershey Medical Center, Hershey, PA
ACKNOWLEDGMENTS We thank Dr. Mazin Dhafir for generously sharing the clinical image in Figure 1 and his patient for permitting publication of the clinical photograph. REFERENCES 1. Fernandez-Flores A, Saeb-Lima M. Spitz nevus intermingling with hemangioma. Am J Dermatopathol. 2016;38:780–783.
2. Wu PA, Mancini AJ, Marghoob AA, et al. Simultaneous occurrence of infantile hemangioma and congenital melanocytic nevus: coincidence or real association? J Am Acad Dermatol. 2008;58:S16–S22. 3. Barnhill RL, Chastain MA, Jerdan MS, et al. Angiotropic neonatal congenital melanocytic nevus: how extravascular migration of melanocytes may explain the development of congenital nevi. Am J Dermatopathol. 2010;32: 495–499. 4. Barnhill R, Dy K, Lugassy C. Angiotropism in cutaneous melanoma: a prognostic factor strongly predicting risk for metastasis. J Invest Dermatol. 2002;119:705–706. 5. Hartley AH, Rasmussen JE. Hemangiomas and Spitz nevi. Pediatr Rev. 1990;11:262–267. 6. Hamm H, Hoger PH. Skin tumors in childhood. Dtsch Arztebl Int. 2011;108:347–353. 7. Arica DA, Arica IE, Yayli S, et al. Spitz nevus arising upon a congenital glomuvenous malformation. Pediatr Dermatol. 2013;30:e25–e26. 8. Zelger BG, Wambacher B, Steiner H, et al. Cutaneous epithelioid hemangioendothelioma, epithelioid cell histiocytoma and Spitz nevus. Three separate epithelioid tumors in one patient. J Cutan Pathol. 1997;24:641–647.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editor 9. Bentolila LA, Prakash R, Mihic-Probst D, et al. Imaging of angiotropism/vascular cooption in a murine model of brain melanoma: implications for melanoma progression along extravascular pathways. Sci Rep. 2016;6: 23834. 10. Tetzlaff MT, Xu X, Elder DE, et al. Angiomatoid Spitz nevus: a clinicopathological study of six cases and a review of the literature. J Cutan Pathol. 2009;36: 471–476. 11. Napekoski KM, Fernandez AP, Billings SD. Microvenular hemangioma: a clinicopathologic review of 13 cases. J Cutan Pathol. 2014;41: 816–822. 12. Trevino-Villarreal JH, Cotanche DA, Sepulveda R, et al. Host-derived pericytes and Sca-1+ cells predominate in the MART1-stroma fraction of experimentally induced melanoma. J Histochem Cytochem. 2011;59: 1060–1075. 13. Detmer DE, Fryback DG, Gassner K. Heuristics and biases in medical decision-making. J Med Educ. 1978;53:682–683. 14. Valiente M, Obenauf AC, Jin X, et al. Serpins promote cancer cell survival and vascular cooption in brain metastasis. Cell. 2014;156: 1002–1016.
www.amjdermatopathology.com |
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
3
