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Natural History, Mimicry, and Sleepless Nights


Mark A. Hurt MD

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By Mark A. Hurt, MD

[b]Definitions[/b]

Natural History -- The natural development of something (as of an organism or disease) over a period of time. ("natural history." Webster's Third New International Dictionary, Unabridged. Merriam-Webster, 2002. http://unabridged.merriam-webster.com (6 May 2012).)

Mimicry -- A superficial resemblance that some organisms exhibit to other organisms or to the natural objects among which they live and thereby secure concealment, protection, or some other advantage. ("mimicry." Webster's Third New International Dictionary, Unabridged. Merriam-Webster, 2002. http://unabridged.merriam-webster.com (6 May 2012).)

[i]It is an old conflict, and it is one that all dermatopathologists must face in their careers. Why must they face it? Before I answer, allow me to provide an example of the problem.[/i]

Recently, I attended on the case of a woman's biopsies taken from her back, two biopsies from the same lesion. The case was referred to me because one of my associates discovered that I had attended on an earlier biopsy, from the same location, in 2008. My diagnosis then was a junctional lentiginous melanocytic nevus.

Both of the current biopsies contained melanoma, at least in situ. There was an area on one of the biopsies that contained a dermal component of melanocytes within a scar, so I reasoned that it was possible that the dermal component could have been part of a melanocytic nevus.

What was striking, however, was the biopsy from 2008. It contained features, in retrospect, that were similar, somewhat, to the melanoma in situ of the current case, but the features were not as well developed; there was sparing of the suprapapillary plates in most areas, and the melanocytes were confined mainly to the tips of the retia. Even with the use of Melan-A and even in retrospect, the features supported the histopathology of a melanocytic nevus, in my opinion.

I had 24 hours to think about this case before I contacted the dermatologist. My thinking ranged from the question of whether I was simply wrong about the biopsy from 2008 to whether melanoma mimicked a melanocytic nevus to whether there was a nevus in 2008 and, perhaps, there was a sampling issue that precluded me from identifying that both nevus and melanoma were in the same lesion. It was a sleepless night, as I turned this over, again and again, in my mind.

I decided, ultimately, to simply explain this differential on the report, and I discussed it with the clinician, who, to my relief, understood fully my dilemma. He even explained to me how this happens to him with clinical lesions.

So, back to my initial statement: It is an old conflict, and it is one that all dermatopathologists must face in their careers. Why must they face it?

The answer is this: we must face it because the natural history of a malignancy includes morphological patterns that mimic benign lesions.

Early in my career, I once held that benign lesions could "transform" to malignant ones; I no longer hold this to be true. What really happens is that lesions begin as small versions of what we learn to recognize when they become classic lesions (as presented, say, in a textbook). It is tempting to think that "transformation" can occur, but that's like saying that when you are born you are one person, and you transform to another person when you are 10, and still another when you are 40. No. That is not what happens to a person, and it is not what happens to a lesion.

The natural history of a person is to begin as an infant, to grow to a child, then to an adolescent, then an adult, then to die in old age, unless interrupted by accident or disease.

The natural history of a neoplasm is to begin as a rudimentary version of what we learn to recognize later as a classic version; if it were not this way, it would be impossible to develop a concept of natural history, because whatever we observed would be impossible to categorize. Melanomas begin small; they don't "transform" from nevi. It is true that they can develop from a melanocyte within a nevus (whether "of" the nevus or a control melanocyte "in" the nevus), but this is the exception, and when it happens, the entire nevus doesn't "transform"; rather, a melanocyte transforms by complex mechanisms that basic scientists are only beginning to discover.
As diagnosticians, we are concerned with mimicry, not with "transformation." It is mimicry that is the constant challenge, diagnostically, and it is mimicry that is the fundamental basis for the development of a differential diagnosis.

Unfortunately, this realization will not prevent a few sleepless nights, but it might help clarify the diagnostic problems that we all face from time to time. This is the nature of our work as dermatopathologists.
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I am a bit confused Dr. Hurt. Are you saying that benign lesions do not become malignant and that malignant lesions do not arise from benign precursors?
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Mark A. Hurt MD

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A cell can transform, but not a lesion, as such. The source of the cell can be a control cell or a cell from within a lesion (presumably).

I have postulated that there are even control cells within some benign lesions. For instance, are all melanocytes within a nevus part of the nevus? Perhaps some, if not many, are native or control melanocytes. This might explain some of the examples of nevus in conjunction with melanoma, the latter arising within control melanocytes.

Thus, in my view, malignant neoplasms can arise from control cells within control skin, from control cells within a lesion (either malignant or benign), or, conceivably, from a cell of a benign or malignant neoplasm (possibly explaining mixed differentiation in some neoplasms).

The point I am attempting to make is that the changes are mediated through cells, not lesions.
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Dr. Hafeez Diwan

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An excellent post! This is a dilemma that we all face. Hindsight, as they say, is 20/20. I once had a similar experience with a post-radiation angiosarcoma. It looked so, so innocuous in the initial biopsy - not one in a thousand would have called it angiosarcoma. But then it mushroomed into a full blown angiosarcoma. When I went back to review the original biopsy, I had a similar experience to the one you have described.
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