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Dermatopathology: Practical & Conceptual April - June 2008
5. New Heights: “Animal-type” melanoma and entities related to it (Part I): Evolution of a concept
François Milette, M.D.
A. Bernard Ackerman, M.D.
Contents of Part I
I. Melanosis in horses and men? (Dick, 1832)
II. A précis of equine melanotic disease (Levene, 1971)
III. Melanoma arising in “blue nevi”? (Darier, 1925)
IV. Diffuse mesodermal pigmentation? (Carleton and Biggs, 1948)
V. Melanotic disorders in horses and men? (Levene, 1979)
VI. Pilar neurocristic hamartoma? (Tuthill, Clark, and Levene, 1982)
VII. Malignant melanoma arising in a blue nevus? (Pathy, Helm, Elston, Bergfeld and Tuthill, 1993)
VIII. Cutaneous malignant melanotic neurocristic tumor arising in neurocristic hamartoma? (Pearson, Weiss, Headington, 1996)
IX. Malignant melanoma with prominent pigment synthesis: “Animal-type melanoma”? (Crowson, Magro, Mihm, 1999)
X. Animal type melanoma? (Requena, de la Cruz, Moreno, Sangueza, Requena, 2001)
XI. Animal-type melanoma? (Kazakov, Rütten, Kempf, Michal, 2004)
XII. In the textbooks?
XIII. Melanomas in horses as described in veterinary medicine literature? (Valentine, 1995; Seltenhammer, 2004)
III. Melanoma arising in "blue nevi"? (Darier, 1925)
Darier is purported to have reported on "cellular blue nevus," but under a designation different, namely, "melanosarcoma," he having compared it to the disease melanotic in horses.
In an article lengthy in which Darier sought to demonstrate the existence (beside the "nevocarcinoma" often beginning in the epidermis [which he, himself, had presented earlier in 1913]) of a lesion melanocytic devoid of a component intraepidermal, he believing that it originated from special "mesenchymal melanoblasts" rather than from "epithelial melanoblasts" positioned at the base of the epidermis. [
] Darier wrote at a time when debates lively were routine concerning the nature (epithelial vs. mesenchymal) of the cells responsible for producing melanin. In order to elaborate on his thesis, Darier told of three patients with lesions of character different.
Darier's Patient 1 had a melanoma that developed in an agminated congenital "blue nevus" situated on the neck. The behavior malignant of it became apparent when the patients was age 22 in the form of progressive adenopathies eventuating in a state of cachexia and death, at age 36, a course of 14 years. No autopsy was performed so that no determination could be made about extension of cells neoplastic to internal organs. This history is of a situation straightforward: a melanoma arose in a congenital nevus, metastasized, and caused death. Unfortunately, the drawing in the article of Darier consists only of histopathologic findings representative of the congenital component benign and not of any of the one malignant.
Patient 2 was a 17-year-old girl with a blue lesion present since birth that grew slowly to attain a size of 9 x 7 centimeters. Some nodularity was appreciated on palpation, but adenopathy could not be detected. The drawing by Darier of a section of tissue of the specimen obtained after treatment of the lesion by electrolysis shows characteristics of a congenital nevus of the type designated conventionally "blue." There was no sign of recurrence of the lesion after 2 years.
Patient 3 had a macular and nodular bluish lesion on the neck at the site of resection earlier (at age 11) of what was said to be an angioma that had not been subjected to examination by microscopy conventional. The patient was in poor health, but adenopathy palpable was noted to have regressed in the absence of therapy, an indication that the cause of the enlargement of lymph nodes was a process inflammatory. The lesion in the skin was treated by electrolysis and disappeared. Re-excision after treatment showed only a scar without any melanin residual. Because the lesion did not recur after six years, the patient was considered by Darier to be cured.
Although follow-up may not have been of length sufficient to assess adequately the course of the processes in two of the three patients, the description of histopathologic findings in all of them was consonant with a type of congenital nevus, in one of which a melanoma came into being.
In his discussion, Darier likened the lesions in his three patients to melanotic disease in horses. This is what he wrote in that regard:
"In horses melanosis grows progressively but slowly. Horses do not die of the disease except from secondary hemorrhage or rupture of the spleen. They are sacrificed when they become cachectic because of destruction of viscera by huge metastases."
(translated from the French by F.M.) [
But is the description of Darier of attributes in these horses in keeping only with metastases of melanoma? What about the slow growth of the lesions? Need a melanoma always have a course "aggressive"?
His recognition of parallels notwithstanding, the lesions presented by the patients of Darier were in many ways different from equine melanocytic disease. For one, two patients were considered "cured," whereas in horses surgery does not affect the course. Second, the lesions were monocentric, whereas in horses they are multicentric. Third, they occurred in young individuals and even may have been congenital, whereas they appear late in the life of horses.
Darier seems to have been impressed by the pace petty at which the diseases progressed both in his patients and in horses. That, along with pigmentation intense, was the main resemblance between the two circumstances, it being communicated by him in the sentence following:
"The slow evolution of horse melanosis is like what I observed in humans . . ."
] That Darier also was aware of differences is apparent in this statement by him:
"However in humans the formation of huge tumors is reduced to a minimum."
] Nevertheless, Darier's Patient 1 died secondary to dissemination of the process neoplastic and it is apparent that "formation of huge tumors" in that patient was not "reduced to a minimum."
In sum, we interpret the lesions in Darier's three patients to be congenital nevi of the type referred to conventionally as "blue nevus." In one of the three, a melanoma developed and was responsible, ultimately, for death.
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