ARTICLE
Auteur(s) : Jason B Lee
Department of Dermatology & Cutaneous Biology, Thomas
Jefferson University Hospital, 833 Chestnut Street, Suite 704,
Philadelphia, PA 19107, USA, Fax (+1)-215-503-4317
Differentiating a Spitz nevus from a melanoma is one of the
thorniest diagnostic conundrums for a histopathologist [1]. A
mistake in this diagnosis has profound consequences, for over
treatment may result in mutilating surgery and under treatment may
result in death. Why is differentiating a Spitz nevus from a
melanoma so difficult? Spitz nevus often has cytologic features
that are normally associated with malignant neoplasms, namely,
atypia and mitosis. In her 1948 seminal article “Melanomas of
childhood,” Sophie Spitz described 13 cases of what she thought
were authentic melanomas because of the presence of cytologic
features that were indistinguishable from those present in adult
melanomas [2]. But of the 13 cases, only one proved to be fatal and
the rest of the cases represented the eponymous melanocytic nevi,
that is, Spitz nevi. Because, at times, the distinction between
Spitz nevus and melanoma is difficult and may be impossible, new
designations of melanocytic neoplasms have emerged, which has
fueled further confusion for clinicians rather than clarification.
The new designations include atypical Spitz tumor, metastasizing
Spitz tumor, malignant Spitz nevus, borderline and intermediate
melanocytic tumor, and melanocytic tumor of uncertain malignant
potential (MELTUMP) [3-5]. What is not clear in all of these
designations is whether the issue is the inability of the
histopathologist to discriminate between benign and malignant, in
which case they represent euphemisms for “I don’t know,” or whether
the issue is that these difficult lesions actually lie somewhere
between the spectrum of benign and malignant in accordance with the
muti-step theory of carcinogenesis. And if they do lie somewhere
between benign and malignant, what place exactly in the spectrum
does the lesion occupy, toward benign or toward malignant?What is
clear in the realm of melanocytic neoplasms is that disagreements
about the nature and diagnosis abound among histopathologists,
particularly when it comes to Spitz nevus and melanoma. In 1990,
ten expert histopathologists were asked to render their opinions on
37 cases of classic melanocytic neoplasms in a National Institutes
of Health sponsored event titled Workshop without Walls [6]. There
was complete agreement in only 35% of the cases. A decade later in
2000, at the 21st Symposium of the International Society of
Dermatopathology, 6 expert dermatopathologists were asked to render
their opinions on 67 difficult melanocytic lesions [7]. There was
complete agreement in 49% of the cases. In the category of Spitz
nevus, the complete agreement was only 25% and in the category of
nevoid/spitzoid melanoma, 33%.Why the lack of concordance? In the
era of flow cytometry, polymerase chain reaction, and DNA
microarray, the gold standard for diagnosing melanocytic neoplasms
is still routine light microscopy. Unlike aforementioned tests
where precision and accuracy may be verified and corrected,
interpretation of hematoxylin and eosin sections at the microscope
is wholly subject-relative. A given lesion may be interpreted as an
atypical Spitz nevus by one histopathologist but as a typical one
by another, a borderline lesion by one but non-borderline by
another, and the malignant potential may be known by one but not by
another. Concordance rate is unlikely to improve in the near future
because a histopathologist can opine what the nature of a
particular lesion is, but there is no way to verify the accuracy of
the opinion in most cases, except for those few cases in which
metastasis results in death. Most questionable lesions, whether
they are in reality benign, malignant or lie in the spectrum
between benign and malignant, are completely removed often with
wide margins. Case and point, the ( figure 1A ) to D show a
melanocytic proliferation that was seen in consultation by two
expert dermatopathologists. The opinions were polar opposite: Spitz
nevus and melanoma. Who was correct? Excision with wide margins and
sentinel node dissection were performed concomitantly. The sentinel
node was uninvolved. Was the patient saved from a potentially
deadly disease or was the surgery and the lymphedema that resulted
from the surgery wholly unnecessary? How will we know?The lack of
concordance among histopathologists led to outcries for
standardizing terminology, definitions, and criteria. Even if every
histopathologist agrees on terminology, definitions, and criteria,
correct and consistent application of the criteria is another
matter. The methodology at the microscope, for the most part,
works. Every medical student can be taught to recognize, for
example, Henderson-Patterson bodies of molluscum contagiosum,
infundibular tunnels of seborrheic keratosis, and multinucleated
epithelial cells of herpesvirus infection. When the diagnosis is
based on one or two identifying histopathologic changes, rarely are
there disagreements and errors in judgment, but when the criteria
consist of a table with a long list of differentiating features [5,
8], frequently are there disagreements and errors in judgment.
Diagnosing diseases through the microscope is dependent not only on
the training and the experience of the histopathologist, but also
on the predisposition (mood, fatigue, mental acuity, etc.) of the
person at the microscope at the moment the judgment is rendered.
That is, judgments rendered at the microscope are subject to
fallibility of the mind. As the saying goes, “To err is human.”
When the diagnosis is based on a long list of criteria, the mind is
more prone to err even if the criteria do work. Thus, when an error
in judgment occurs at the microscope, the sources of the error may
be due to inability of histopathologist, human error, and/or due to
the failure of the diagnostic methodology itself employed by the
histopathologist.The matter of Spitz nevus has exposed the
limitation of the diagnostic methodology most commonly employed by
a histopathologist. There will be always melanocytic lesions that
are unconventional, which are difficult to interpret, and unanimity
in opinion will be the exception rather than the rule. The current
methodology does not consistently discriminate what in reality is
benign, malignant, or “borderline.” In addition, the accuracy of
the diagnoses rendered at the microscope cannot usually be measured
when it comes to these unconventional cases. One day a more
accurate and precise test may emerge as an objective arbiter for
these unconventional melanocytic neoplasms, but until such a test
becomes the gold standard, discordance and controversy will not
cease and clinicians and histopathologists must acknowledge the
limitation of the current diagnostic method.
Acknowledgements
The illustrated case was provided by Dr. Carmen Campanelli.
References
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25: 223-38.
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