Case 5 -
Skin, back: Malignant melanoma, nodular type, ulcerated, with epithelioid tumorigenic and mitogenic vertical growth phase, and Spitzoid features, extending to Clark's level IV at a greatest Breslow thickness of at least 1.1 mm, transected at the specimen base
David E. Elder, Hospital of The University of Pennsylvania, Philadelphia, PA
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- A 9 year old child presented with a nodular lesion of the back.
- The lesion had appeared suddenly and grown rapidly over several weeks, more recently developing a crust and occasionally bleeding.
- A fragment of skin was received, with a central ulcerated nodule.
Case 5 - Figure 5
Tumor cells are arranged in nests, rather loosely placed in a vascular fibrous stroma.
Case 5 - Figure 6
Frequent mitoses are present (e.g. in the green circle).
Case 5 - Figure 7
The tumor cells at the base resemble those near the surface (failure of maturation) - compare with figures 4 and 5. Mitotic activity is also present near the base.
This nine-year-old child presented with a lesion of the back that had appeared suddenly and grown
rapidly, developing a crust which had recently bled, causing spotting of his sheets and clothing.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Histological sections showed a moderately to highly cellular nodular tumor comprised of relatively
large epithelioid cells which were melanocytic as judged by MelanA and S 100 reactivity. The cells were
arranged mainly in nests, extending from near the surface which was extensively ulcerated, to the base of
the biopsy specimen. There was no evidence of maturation from superficial to deep. There was no
extensive in situ component of a melanoma and no characteristic junctional component of a nevus, although
the lesional cells appeared to be in contact with the epidermis at the edges of the ulcer. Although the
possibility of a benign Spitz nevus/tumor was considered, this lesion did not demonstrate the typical
"large spindle and/or epithelioid" cell type of Spitz tumors, and nor did it have a characteristic
junctional component. However, a single Kamino-like body was noted in a superficially located dermal
nest. The presence of extensive consumption of the epidermis and of extensive ulceration was also
against the diagnosis of a Spitz tumor. Finally, the dermal mitotic rate was very high at 11 per square
millimeter. The ulcer was greater than 3 mm in diameter. Radial growth phase regression, microscopic
satellites, and vascular, lymphatic or neural invasion could not be satisfactorily evaluated in this
superficial biopsy. For these reasons, this lesion was interpreted as follows below. A subsequent
reexcision procedure was negative for residual tumor. Multiple axillary sentinel nodes were biopsied,
and one of these contained deposits of metastatic tumor, in the form of scattered small metastatic tumor
deposits within the sinus and superficial parenchyma. Four additional sentinel nodes were negative for
tumor. These findings were interpreted as follows below.
Differential diagnoses include an ulcerated compound nevus, a Spitz nevus/tumor, an atypical Spitz
nevus/tumor, a Spitzoid melanoma of childhood, or a malignant melanoma.
Skin, back: Malignant melanoma, nodular type, ulcerated, with epithelioid tumorigenic and mitogenic vertical growth phase, and Spitzoid features, extending to Clark's level IV at a greatest Breslow thickness of at least 1.1 mm, transected at the specimen base. Right Axillary Sentinel Node Number
Three, Biopsy: Metastatic Melanoma involving one lymph node (1/1), without extracapsular extension.
Skin and Subcutaneous Tissue, Right Lower Back, Wide Excision: Scar and healing surgical site changes,
no residual melanoma identified.
This case exemplifies the difficulty in diagnosing Spitzoid tumors in patients of all ages. These
lesions are most common in children. Metastasis to sentinel nodes is surprisingly common in these
lesions, however the overall survival experience has been excellent in a number of reported series,
albeit with somewhat limited follow-up intervals.
Review of the Literature/Treatment Options (if applicable):
The lesion described by Sophie Spitz has caused problems of interpretation ever since her seminal
publication . Initially, these were thought to be "juvenile melanomas", perhaps with a better
prognosis than adult melanomas. However, one of the lesions described in her paper had resulted in the
death of the child. Although most of these lesions are indeed benign, similar difficulties of prediction
persist to this day in some atypical lesions which are rare in routine practice but common in
consultation practices. It has therefore become the rule to refer to these lesions as "Spitz tumors"
rather than "Spitz nevi" . The term "melanocytoma" has also been used recently to convey a sense that
the behavior of these lesions is somewhere between benign lesions (the usual situation), or lesions with
various degrees of malignancy . The single defining characteristic of a typical Spitz tumor is the
presence of large spindle and/or epithelioid cells, a term attributable to Ackerman . Characteristic
Spitz tumors are small and symmetrical. The lesional cells are characteristically monotonously similar
from side to side across the lesion at any given level, and show evidence of maturation to a smaller cell
type toward the base. At the base, the cells disperse as single cells into the reticular dermis. The
overlying epidermis is typically hyperplastic without evidence of "consumption of the epidermis" or
ulceration. Curious globoid eosinophilic "Kamino bodies" are typically present near the interface.
Typically there is little or no pagetoid scatter of lesional cells into the epidermis above the dermal
component or adjacent to it. The mitotic rate is generally low, without abnormal mitoses and without
mitoses in the lower third of the lesion . Deviations from this ideal morphology may lead to
characterization of the lesions as representing "atypical Spitz tumors", "Spitzoid melanocytomas of
uncertain malignant potential", or "Spitzoid melanomas", depending on their severity . Criteria for
Spitz tumors as discussed above will usually permit a competent distinction of these lesions from
invasive melanoma. However, some lesions demonstrate hybrid characteristics between classical Spitz
tumors and vertical growth phase melanoma. These diagnostically challenging lesions have been termed
"atypical Spitz tumors", as has been proposed by Barnhill and Spatz and colleagues
lesions, it was proposed that points could be assigned if certain features were present (designated by
asterisks in Table I). A patient age of > 10 years or a diameter > 10 mm are each assigned 1
point, the presence of fat involvement, of ulceration or a mitotic rate of 6-8 per square mm are each
assigned 2 points, and a mitotic rate of > 8 is assigned 5 points. On this scale, 0-2 points
indicates low risk, 3-4 indicates intermediate risk, and 5-11 indicates high risk. This system worked
well in a series of 30 childhood Spitz tumor patients, eleven of whom had a history of metastasis and 19
of whom had long disease-free follow-up. However, validation in an external system is required, and
therapeutic guidelines do not readily flow from this classification. Another study of 33 cases of Spitz
tumor and 19 of malignant melanoma in patients aged 20 years or less identified prominent pagetoid
spread, cellular pleomorphism, nuclear hyperchromasia and mitotic activity as the most striking
differences between Spitz tumors and melanomas. These authors stressed the importance of cytological as
well as architectural features in distinguishing between these two groups, and emphasized that there is
overlap in the histologic features . Although it is well known that mitoses may be seen in Spitz
tumors, the mitotic rate is generally very low. Commonly there are no mitoses at all in a Spitz tumor.
Failure to find mitoses after a careful search can be a very reassuring negative finding in a lesion that
may have given rise to concern for some other reason, such as the presence of a few cells in the
epidermis, or its size and depth. While mitoses may be seen in Spitz tumors, they are most common in the
epidermis and in the upper third of the dermis; mitoses in the lower third of the lesion are uncommon
except in young children . Abnormal mitoses are quite rare in Spitz tumors
, although it is said
that they may occur . Certainly, a clearly abnormal mitotic figure should prompt careful
consideration of other aspects of the lesion before an unqualified benign diagnosis is issued. Few if
any benign Spitz tumors exhibit a "high" mitotic rate (more than 6 mitoses per square mm). In the
studies of Crotty et al, the presence of abnormal mitoses, a dermal mitotic rate of >2/mm2, and
mitotic figures within 0.25 mm of the deep border of the lesion were features that favored melanoma .
In Spitz tumors, mitotic figures may be seen in hyperplastic keratinocytes, a finding rare in common
nevi, but not unusual in melanomas. Spontaneous ulceration or necrosis is very uncommon in a benign
Spitz tumor , as is the interesting phenomenon of "consumption of the epidermis" . There are a
few ulcerated Spitz tumors that presented with a history of trauma, especially in children who may pick
at these occasionally itchy lesions. Spitz tumors that show several of the atypical features discussed
above may be very difficult to distinguish from melanoma, and sometimes a descriptive diagnosis is all
that can be rendered in a very difficult case. In a study in which nine cases selected for their
diagnostic difficulty were circulated among "expert" pathologists, the reproducibility of the diagnosis
of Spitz tumor was very poor . In another study of diagnostic reproducibility for selected difficult
and metastasizing lesions each of which exhibited some criteria for the Spitz tumor, evaluation of 17
Spitzoid lesions, some of which had metastasized, yielded no clear consensus as to diagnosis; in only one
case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably,
some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz
tumors . Yet another study of diagnostic reproducibility found disagreement to be concentrated in the
category of Spitz tumors" and "Spitzoid" melanomas, for which there was a 35-40% overall disagreement
rate among 6 reference pathologists who reviewed a series of 72 cases chosen for their potential
diagnostic difficulty; in contrast the agreement was very good for most other categories of lesions .
Metastasis of "Spitzoid" lesions, although uncommon, cannot be dismissed as a possibility in an atypical
Spitzoid lesion. In a literature review, Urso found about 100 cases of "metastasizing Spitz tumors".
Although histologic data were not uniformly recorded, this review indicated that any number of the
following histologic features could be found in a metastasizing lesion : 1. Nodular growth in the
dermis and/or large confluent, solid, cellular sheets with no collagen fibers interposed between cells.
2. Extension of the neoplastic proliferation to the mid-deep dermis or to subcutaneous fat, especially if
associated with absent or impaired maturation. 3. Dermal mitoses, especially in the deeper part of the
tumor. 4. Marked nucleolar and/or nuclear pleomorphism. 5. Heavy melanization in the deeper part of the
tumor. 6. Asymmetry. 7. Necrosis. 8. Epithelioid epidermal melanocytes below parakeratosis and/or
epidermal ulceration. 9. Neoplastic cells in lymphatic vessels. Many of these tumors, in our opinion,
are best regarded as "melanocytic tumors of uncertain malignant potential. Recently, a group of cases
assembled by Lorenzo Cerroni, MD was studied by a group of experts and discussed at the annual meeting of
the International Society of Dermatopathology in Graz, Austria . These cases were selected as bulky
tumors comprised of a uniform population of epithelioid or spindled cells. Not all were especially
"Spitzoid"; some had features of deep penetrating nevi, pigmented epithelioid melanocytomas, or cellular
blue nevi. Despite the size of the lesions, only a few small ulcers were observed and there was no in
situ melanoma component. The lesional cells had abundant cytoplasm with large round or ovoid nuclei with
regular nuclear membranes, pale chromatin and a single prominent nucleolus. Mitoses were absent in many
lesions and if present the rate was low. About one third of these lesions had metastases, most often to
regional nodes, and about 20% were fatal, often after a protracted at least initially indolent course.
There were several instances of relatively long term survival after regional metastases, suggesting that
some of these metastases, like the primary lesions, may be of uncertain malignant potential. It was
considered that these lesions represented a form of relatively low grade malignancy compared to ordinary
melanomas of similar depth, and use of the term melanocytoma was suggested as an expression of their
intermediate characteristics between benign nevi and malignant melanomas. In addition to being
noncommittal about prognosis, this term could encompass the range of morphologies observed in these
lesions. Risk factors for aggressive behavior included the presence of mitoses, mitoses in the lower
third of the lesion, and the presence of a lymphocytic infiltrate. Tentatively it has been proposed to
classify these lesions into four risk groups: Minimal risk with none of these adverse factors, low risk
with one of them, intermediate risk with two, and high risk with all three of the factors. Greater
pigmentation and older age also correlated adversely with behavior to a lesser extent. Although as a
gross generalization it may be true that "difficult" lesions are usually benign in terms of long-term
follow-up , this is not invariably so. In our opinion, equivocal lesions exhibiting conflicting
between those of benign and Spitz tumors and Spitzoid melanomas, if considered to fall short of an
unequivocal diagnosis of melanoma, should be classified as "melanocytic tumors of uncertain potential
(MELTUMP)" and the differential diagnosis of melanoma should be presented, with a discussion of staging
attributes. More aggressive management of these atypical Spitz lesions may be warranted , and this in
our opinion should be tailored to the individual case, including analysis of prognostic attributes that
might apply if the lesion were interpreted as a melanoma. Management of problematical "Spitzoid" lesions
should usually include a re-excision procedure, and follow-up of the patient. A sentinel lymph node
sampling procedure may also be considered. In several reported studies the sentinel node has not
uncommonly been positive
Interestingly, among these multiple reported cases of patients with
atypical Spitzoid lesions and positive sentinel nodes, recurrences and especially deaths have been very
rare. A recent study concluded that "pediatric patients have a higher incidence of SLN metastases than
adults yet have a lower incidence of recurrence", and further "Sentinel lymph node status does not
predict early recurrence in pediatric patients with melanoma or atypical Spitz nevi" . Therefore, it
seems likely that atypical Spitzoid lesions and even "Spitzoid melanomas" (at least those in children)
may be associated with excellent survivals even after the finding of a positive sentinel node metastasis.
For this reason, we will typically sign out these cases as "metastatic melanocytic tumor of uncertain
malignant potential", recognizing that this is a descriptive and not a definitive diagnosis.
In our present case, because of the very high mitotic rate, the ulceration, and lack of maturation of
the dermal component, as well as other features, we regarded this young patient as having a malignant
melanoma, with features consistent with a "Spitzoid melanoma of childhood". As discussed above, the
prognosis is unpredictable, but better than one might expect for a usual form of melanoma with the same
attributes. Currently, about 6 months after his sentinel node procedure, he remains free of disease.
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