August 2013 Case 1

A 40 year old Caucasian male presented with a raised lesion on the left buttock

Ryan Okal, M.D., Melina Flanagan, M.D., Jeffrey Stead, M.D.


A 40 year old Caucasian male presented with a raised lesion on the left buttock. The lesion was excised.

Gross Description

Specimen consisted of a 4.2 x 2.0 cm skin ellipse overlying a 3.0 x 2.0 x 2.0 cm lesion which is red-brown, soft, and partially cystic, with a focus which is tan and firm (figure 1). Microscopic examination shows an uninvolved epidermis (figure 2). The lesion is in the dermis and is highly cellular with a biphasic pattern consisting of nested/ neuroid structures (figure 3) and fascicular areas (figure 4). Prominent pigmentation is seen throughout the lesion and rare mitoses are identified (figure 5).

Ancillary studies were performed. A MIB-1 (Ki-67) stain did not show an increase in proliferative activity (figure 6). A four probe FISH panel (Melano-site) was negative.

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Figure 1
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Figure 2
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Figure 3
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Figure 4
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Figure 5
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Figure 6


What is the most likely diagnosis ?


Please select an answer above.


Cellular blue nevus (CBN) is a variant of the more frequently encountered classical or common blue nevus. The typical features of a cellular blue nevus include a normal epidermis with spindle shaped melanocytes in the dermis[6]. The increased cellularity and the biphasic growth of the case depicted represent the main distinguishing features between. The lack of necrosis and mitoses would favor a benign entity instead of a melanoma or malignant blue nevus. The size of this lesion (3 cm) and presence of mitotic activity are features that some authors would consider atypical.

Some controversy exists as to when to classify a CBN as atypical. Some authors consider any mitotic activity an indication for calling the lesion atypical [4,5,7], while other authors require higher rates of mitotic activity [2,3]. These same authors also disagree on the size necessary for a diagnosis of atypia – ranging from greater than 1 cm to greater than 3cm.

A general consensus on true criteria distinguishing a cellular blue nevus from atypical and more malignant counterparts seems to still be debatable. One study has shown that when reviewing a series of cases including melanomas, cellular blue nevi, atypical cellular blue nevi, and blue nevi, a majority consensus was not reached in 73% of cellular blue nevi cases[1].
The Melano-site 4 probe cocktail is performed by fluorescence in situ hybridization (FISH). The four probes used target RREB1 (chromosome 6), CEN6 (chromosome 6), MYB (chromosome 6), and CCND1 (chromosome 11). In this specimen, the signaling patterns were all within normal ranges. The reported validation by NeoGenomoics showed that a negative result had 98% specificity for benign nevi without atypia. Of note, however, 16% of melanomas studied also had a negative result.
CBN is infrequently seen in clinical practice. High cellularity and pigmentation may cause even experienced pathologists to be concerned about the possibility of malignant melanoma. Recognizing the biphasic growth pattern, lack of junctional component and necrosis, and relative lack of mitotic activity should allow an appropriate diagnosis most of the time. For problematic cases, additional evidence supporting a benign diagnosis may be obtained by demonstrating a low MIB-1 proliferation rate by immunohistochemistry and by molecular testing, as described above.
The lesion was reported as an atypical cellular blue nevus. Additional tissue subsequently removed from the area did not reveal any residual CBN. Complete excision and clinical follow up is recommended for CBN.


  1. Barnhill, et al. Atypical cellular blue nevi (cellular blue nevi with atypical features): Lack of consensus for diagnosis and distinction from cellular blue nevi and malignant melanoma (“malignant blue nevus”). Am J Surg Pathol. 2008;32: 36-44
  2. Busam KJ, Barnhill RL. Dermal melanocytosis, blue nevi and related conditions. In: Barnhill RL, Piepkorn M, Busam KJ, eds. Pathology of Melanocytic Nevi and Malignant Melanoma. 2nd ed. New York: Springer-Verlag; 2004.
  3. Caloneja, E., Brenn, T., Lazar, A., and McKee, P. Mckee’s pathology of the skin. Fourth edition. China: Elsevier Saunders. 2012; 1216-17.
  4. Elder DE, Murphy GF. Melanocytic Tumors of the Skin. Atlas of Tumor Pathology. Washington: AFIP; 1990.
  5. Maize JC Jr, McCalmont TH, Carlson JA, et al. Genomic analysis of blue nevi and related dermal melanocytic proliferations. Am J Surg Pathol. 2005;29:1214–1220.
  6. Rapini, R. Practical Dermatology. Second Edition. China: Elsevier Saunders. 2012; 277-306.
  7. Tran, T.A., Carlson, J.A., Basaca, P.C., et al. Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases. J Cutan Pathol. 1998;25:252–258.