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Background
The blue nevus is a variant of a common mole. It is composed of melanocytes, the cells which produce the melanin pigment, which have a spindled to epithelioid appearance. This nevus gets its name from the distinct clinical appearance because of the pigmented cells within the dermis. It is benign and is usually more of a cosmetic problem.
On a personal note, when I was a first year medical student, learning physical examination, my physician preceptor noted a mole on my back. He told me that he thought it was benign but because it was blue, I should have it removed. I didn't know if he was joking when he then told me, "I don't know much about dermatology but I do recall being told that if it is blue, it is BAD!" I rushed over to the dermatologist's office who performed the biopsy. One week later, this was the diagnosis. I am not sure if this incident precipitated my interest in dermatopathology but it certainly increased my paranoia about pigmented lesions! (PKS)
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Tieche's nevus
Blue nevus of Jadassohn-Tieche
CLINICAL VARIANTS CHARACTERIZATION ERUPTIVE MULTIPLE BLUE NEVI OF THE PENIS
Eruptive multiple blue nevi of the penis: a clinical dermoscopic pathologic case study.
De Giorgi V, Massi D, Brunasso G, Salvini C, Mastrolorenzo A, Zuccati G, Carli P.
Department of Dermatology, and Department of Human Pathology and Oncology, University of Florence, Florence, Italy.
J Cutan Pathol. 2004 Feb;31(2):185-8 Abstract quote.
Multiple blue nevi have rarely been reported, and the majority of the lesions are located on the trunk and lower extremities. The blue nevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions such as genital melanocytic macules, lentigo simplex, and malignant melanoma.
Here, we describe an unusual patient who presented with a sudden onset in adulthood of multiple blue nevi on the glans penis. The epiluminescence examination revealed a substantially homogenous bluish pigmentation, which led us to favor a diagnosis of blue nevus, whereas not entirely excluding the possibility of a regressing melanoma or a metastatic melanoma.
Because of the well-known diagnostic value of the blue hue in the diagnosis of malignancy by dermoscopy, a careful examination of these lesions should be made in order to minimize any risk of misclassification with melanoma.GIANT CONGENITAL BLUE NEVUS
Giant congenital cellular blue nevus of the scalp of a newborn with an underlying skull defect and invasion of the dura mater.Marano SR, Brooks RA, Spetzler RF, Rekate HL.
Neurosurgery 1986 Jan;18(1):85-9 Abstract quote A case of a giant congenital cellular blue nevus of the scalp of a newborn with focal areas of malignant melanoma is presented. The nevus was associated with focal invasion of the underlying soft tissues, calvarium, epidural space, and dura mater.
The later appearance of pigmented nevi in the submandibular region, sternocleidomastoid muscle, and testicular hydrocele raises the question of future metastases despite the nonmalignant microscopic appearance.
Therapy consisted of total excision with cranioplasty and rotation and split skin grafts after temporary closure with silicone mesh.
HISTOLOGICAL TYPES CHARACTERIZATION General Two main types:
Cellular and common, distinguished by the degree of fibrosis
Pathologic Anatomy Service, Gaetano Rummo General Hospital, Benevento, Italy.
Background: In recent years, several histopathologic variants of blue nevus have been identified, whose clinical and dermoscopic correlates need further clarification.
Methods: A comparative evaluation of histopathologic and dermoscopic features was carried out on 52 melanocytic proliferations belonging to the morphologic spectrum of blue nevus.
Results: On dermoscopy, all lesions showed a homogeneous, structureless pigment pattern, with a curious variety of colors (blue, white-blue, black, brown, and polychromatic). Histopathologically, the majority of blue lesions were common blue nevi (11/19); the majority of white-blue lesions were 'hypochromic' (sclerotic, hypomelanotic, and amelanotic) blue nevi (17/22); all the black lesions were 'compound' blue nevi (2/2); the majority of brown lesions were combined blue nevi (3/4); the unusual polychromatic dermoscopic appearance was often associated with a histopathologic diagnosis of deep penetrating nevus (2/5).
Conclusion: A dermoscopic-pathologic approach now allows us to identify 'blue' (common) blue nevi, 'white' (hypochromic) blue nevi, 'black' (compound) blue nevi, 'brown' (combined) blue nevi, and 'polychromatic' (deep penetrating) blue nevi. A better recognition of the many dermoscopic faces of blue nevi is expected to give a morphologic guideline for the clinical management of these lesions.VARIANTS AMELANOTIC CELLULAR BLUE NEVUS
Amelanotic Cellular Blue Nevus: A Hypopigmented Variant of the Cellular Blue Nevus: Clinicopathologic Analysis of 20 Cases
Artur Zembowicz, M.D., Ph.D.; Scott R. Granter, M.D.; Phillip H. McKee, M.D.; Martin C. Mihm, M.D.Am J Surg Pathol 2002; 26(11):1493-1500 Abstract quote
Blue nevus and its variants typically present as pigmented lesions. Dermal melanin is responsible for coloration and is an expected histologic finding. Herein, we report 20 cases of an unusual amelanotic variant of cellular blue nevus.Our series showed clinical demographics similar to pigmented counterparts. Thus, there was a predilection for young individuals with a mean age of 24 years (range 6-74 years). Both sexes were affected, with a female-to-male ratio of approximately 2:1. The lower back, distal extremities, and scalp were the most common sites of occurrence. Importantly, the lack of pigmentation resulted in an atypical clinical appearance. A diagnosis of blue nevus by the attending physician was not considered in any of the reported lesions. All of the tumors extended deep into the reticular dermis or subcutaneous fat with a mean thickness of 5.5 mm (range 1.7-11 mm). Ulceration was present in two lesions. Mild cytologic atypia and pleomorphism were present in five cases. Mitotic activity (up to 3 mitoses/mm2) was observed in 11 lesions. A brisk lymphocytic host response was present in only one lesion. Tumor necrosis was not observed. Most, but not all, tumors showed reactivity for S-100 and HMB-45.
Clinical follow-up (mean 32 months) was consistent with a benign course. Local recurrence was not observed after complete excision. None of the cases was associated with clinical evidence of lymph node or distant metastases.
Recognition of amelanotic cellular blue nevus is important because the lack of expected pigmentation may result in clinical and pathologic diagnostic difficulty. In particular, amelanotic cellular blue nevus must be distinguished from malignant cellular blue nevus and other variants of melanoma.
ANCIENT BLUE NEVUS
Department of Dermatology, Medical University of Graz, Austria.
Ancient melanocytic nevi are benign melanocytic neoplasms that show degenerative and atypical changes, sometimes leading to a misdiagnosis of melanoma.
We describe 6 patients (M:F ratio 4:2; age range, 15-84 years; median, 50 years) who presented with cellular blue nevi showing stromal changes resembling those of ancient melanocytic nevi. The lesions were located on the buttocks (4 patients) and on the trunk (2 patients) and clinically consisted of heavily pigmented nodules. Histology revealed the architectural pattern of cellular blue nevi. However, the architecture was strikingly altered by stromal changes like those seen in ancient melanocytic nevi, including increased number of large, dilated vessels with pseudoangiomatous features in 4 cases, hyaline angiopathy in 4 cases, myxoid changes, sclerosis or hyalinization of the stroma in all cases, and variable amounts of edema in 4 cases. In 2 cases, a large edematous area was present in the center of the lesion, and nests of ovoidal melanocytes and single dendritic melanocytes appeared to "float" in the stroma. Pleomorphic melanocytes were observed in all cases.
Ancient blue nevi represent a morphologic variation of cellular blue nevi-Masson neuronevi with degenerative stromal changes. Recognition of these lesions can help prevent overdiagnosis of melanoma.CD34-POSITIVE cellular blue nevi
Kathleen J. Smith, etal.
J Cutan Pathol 2001;28 (3):145-150 Abstract quote
Background: Although cellular blue nevi (CBN) are well known and characterized, the histopathologic and clinical spectrum of these tumors continues to evolve. We report four CBN with a distinctive histologic and immunohistochemical pattern.
Methods: The histologic features and immunohistochemical staining for S-100 protein, HMB-45, Bcl-2 and CD34 of four CBN with distinctive features were evaluated using routine methods and compared to common CBN.
Results: All four of these distinctive CBN where known to be congenital, and all showed aggregates of plump spindled cells with round to oval nuclei in aggregates and more slender spindled cells with thin wavy nuclei. The slender, spindled cells showed an infiltrative pattern laterally into the dermis and deep into the subcutaneous fat. All four tumors showed diffuse expression of an immunohistochemical stain for CD34, as well as for S-100 protein, Bcl-2, and HMB-45.
Conclusion: Positive immunohistochemical staining with the progenitor marker CD34 defines a subset of CBN. These tumors appear to fit within the spectrum of neurocristic cutaneous hamartomas and may arise from more primitive neurocristically derived cells. Further follow-up of these tumors will be necessary to determine whether this subset of CBN defines a subset with a characteristic biologic behavior.
ATYPICAL CELLULAR BLUE NEVUS
*Departments of Dermatology and Pathology, University of Miami Miller School of Medicine, Miami, FL †Division of Dermatology, University of Washington School of Medicine, Seattle, WA ‡Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM §Department of Pathology, West Roxbury Veterans Administration Hospital, West Roxbury, MA ∥Department of Pathology, Mayo Clinic, Rochester, MN ¶Departments of Dermatology and Pathology, Northwestern University School of Medicine, Chicago ♯The Dermatology Group, Verona, NJ **Departments of Dermatology and Pathology, University of Michigan, Ann Arbor, MI ††Department of Pathology, University of South Florida and Moffitt Cancer Center, Tampa, FL ‡‡Division of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX §§Rabkin Dermatopathology Laboratory, Pittsburgh, PA ∥∥Department of Pathology, Childrenʼs Hospital and Harvard Medical School, Boston, MA ¶¶Department of Pathology, Duke University Medical Center, Durham, NC ♯♯Division of Dermatology, University of Chicago School of Medicine, Chicago, IL ***Department of Pathology, University of Calgary, Calgary, AB, Canada.
The distinction of cellular blue nevi (CBN) with atypical features ["atypical" CBN (ACBN)] from conventional CBN and malignant melanomas related to or derived from CBN remains a difficult problem.
Here, we report on the diagnosis of various cellular blue melanocytic neoplasms by 14 dermatopathologists who routinely examine melanocytic lesions. Three parameters were assessed: (1) for between rater analyses, we calculated interobserver agreement by the kappa statistic (regardless of whether the diagnosis was correct). (2) For each individual lesion, we reported whether a majority agreement (>50%) was reached and, if so, whether the majority agreed with the gold standard diagnosis, derived from standardized histopathologic criteria for melanoma, definitive outcome such as metastatic event or death of disease, or disease-free follow-up for >/=4 years. (3) For the individual pathologists, we calculated sensitivity and specificity for each type of lesion.
The study set included 26 melanocytic lesions: (1) 6 malignant melanomas developing in or with attributes of CBN; (2) 11 CBN with atypical features and indeterminate biologic potential (ACBN); (3) 8 conventional CBN; and (4) 1 common BN. The kappa values for interrater agreement varied from 0.52 (95% confidence interval 0.45, 0.58) for melanoma to 0.02 (0.05, 0.08) for ACBN and 0.20 (0.13, 0.28) for CBN. The kappa for all lesions was 0.25 (0.22, 0.28). The pathologists' sensitivities were 68.6% (61.0%, 76.1%) for melanoma, 33.1% (21.0%, 45.2%) for ACBN, and 44.6% (29.0%, 60.3%) for CBN. The specificities were 65.7% (55.8%, 75.6%) for melanoma, 84.7% (77.3%, 92.2%) for ACBN, and 89.9% (82.7%, 97.1%) for CBN. Overall, greater than 50% of the pathologists agreed and were correct in their diagnosis 38.5% (10 lesions) of the time. There was a majority agreement, but with an incorrect diagnosis, another 26.9% (7 lesions) of the time. Six of the 7 majority agreements with an incorrect diagnosis were for ACBN lesions.
In summary, the results of our study indicate that there is substantial confusion and disagreement among experienced histopathologists about the definitions and biologic nature of cellular blue melanocytic neoplasms particularly those thought to have atypical features ("atypical" CBN).CELLULAR BLUE NEVUS Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases.
Tran TA, Carlson JA, Basaca PC, Mihm MC.
Department of Pathology, Albany Medical College, New York 12208, USA
J Cutan Pathol 1998 May;25(5):252-8 Abstract quote
Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN.
Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically, they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl-2, and a proliferative index of 23+/-19 and 39+/-30 cells/10 high power field with antibodies to PCNA and Mib-1, respectively.
No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib-1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA aneuploidy in both groups. Follow-up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow-up 42/32 months, range 15-96 months). No patient during this follow-up time has experienced either a local recurrence or lymph node or visceral metastasis.
These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long-term follow-up.
CELLULAR NODULES Large plaque-type blue nevus with subcutaneous cellular nodules.
Busam KJ, Woodruff JM, Erlandson RA, Brady MS.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Am J Surg Pathol 2000 Jan;24(1):92-9 Abstract quote
Unusual or atypical melanocytic nevi can be confused with malignant melanoma. The authors present two cases of an unusual variant of blue nevus that were misdiagnosed initially as malignancy.
Both lesions were asymptomatic and characterized clinically by childhood onset, with slow enlargement during adolescence and subsequent nodule formation. One lesion, which measured 24 cm in greatest dimension, was located on the anterior chest wall of a 53-year-old woman. The other lesion, which measured approximately 15 cm in greatest dimension, was located on the lateral abdominal wall of a 20-year-old man. Both lesions were characterized by a multifocal dermal and subcutaneous proliferation of fusiform and dendritic pigmented melanocytes.
The histologic appearance of individual foci ranged from dermal melanocytosis to common blue nevus and cellular blue nevus. The cellular foci were located in the subcutis and involved, in one patient, the stroma of the breast. The cells were immunoreactive for S-100 protein, gp100 (HMB-45), and Melan-A (A103). Ultrastructural analysis revealed melanocytes typical of blue nevus. The woman underwent complete excision of the lesion, and the man underwent only partial excision of the lesion. On clinical follow-up of 32 and 19 months, respectively, both patients are alive and well with no evidence of recurrence or progression.
Because the lesions presented clinically as large plaques and were diagnosed histologically as blue nevi with subcutaneous foci of cellular blue nevus, we term this rare variant of blue nevus large plaque-type blue nevus with subcutaneous cellular nodules.
Recognition of this lesion enhances our knowledge of the morphologic spectrum of melanocytic tumors and helps to avoid confusion with malignant melanoma.
COMPOUND BLUE NEVUS Arch Dermatol 1990;126:1330-1333
Blue nevus with additional junctional dendritic component“Compound blue nevus”: A reappraisal of “superficial blue nevus with prominent intraepidermal dendritic melanocytes” with emphasis on dermoscopic and histopathologic features
Gerardo Ferrara, MD
Giuseppe Argenziano, MD
Borut Zgavec, MD
Igor Bartenjev, MD
Stefania Staibano, MD
Gaetano De Rosa, MD
H. Peter Soyer, MD
Benevento and Naples, Italy, Ljubljana, Slovenia, and Graz, Austria
J Am Acad Dermatol 2002;46:85-9 Abstract quote
We describe 5 cases of “compound blue nevus” (CBN) (“superficial blue nevus with prominent intraepidermal dendritic melanocytes,” “Kamino nevus”). Dermoscopically in 2 of 4 cases the bluish pigmentation characteristic of blue nevi was centrally replaced by a black lamella, with black dots and brown globules also observed in one case, thus revealing a structural asymmetry suggestive of melanoma.
Histopathologically, pigmented parakeratosis was the underlying histopathologic finding of black lamella and dots/globules. Immunohistochemistry highlighted the unique histopathologic feature of CBN, namely, single dendritic melanocytes at the dermoepidermal junction with striking intraepidermal prolongations.
Our findings confirm that CBN is a distinctive variant of blue nevus that may mimic cutaneous melanoma both clinically and dermoscopically.
EPITHELIOID BLUE NEVUS Am J Surg Pathol 1996;20:259-272
Am J Dermatopathol 1999;21:483-486
J Cutan Pathol 2000;27:218-223
Am J Dermatopathol 2001;22:473-488
Associated with Carney complex but sporadic cases have been reportedTwo types of melanocytes:
A globular, fusiform, or dendritic and densely pigmented
A second with polygonal abundant cytoplasm and variable pigmentationPredominately wedge shaped symmetric lesions within the papillary mid-reticular and upper reticular dermis, extending into the subcutaneous fat, often extending along adnexal structures
May represent an epithelioid combined blue nevus with features of deep penetrating nevus, congenital, and intradermal Spitz (desmoplastic nevus)
May have a junctional component
Distinct HMB45 positive and S100 negative blue nevus componentEpithelioid blue nevus: neoplasm Sui generis or variation on a theme?
Groben PA, Harvell JD, White WL.
Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, USA.
Am J Dermatopathol 2000 Dec;22(6):473-88 Abstract quote
The epithelioid blue nevus has recently been associated with the Carney complex, which is characterized by myxomas, spotty skin pigmentation, endocrine overactivity, and schwannomas.
Using the general criteria proposed by Carney and Ferreiro, similar lesions were identified in 33 patients with no evidence of the Carney complex. Those lesions presented on the face, trunk and extremities of 15 males and 18 females. The mean age was 35 years, much older than those in the Carney complex (mean 16.3 years). Clinical diagnoses included malignant blue nevus, atypical nevus, melanoma, congenital nevus, and dermatofibroma.
The lesions were symmetric, predominantly dermal melanocytic proliferations arranged as short fascicles, small nests, and single cells. Large polygonal and epithelioid melanocytes with moderate pleomorphism, and occasional nuclear pseudoinclusions were admixed with heavily pigmented dendritic and spindled melanocytes and melanophages. Rare mitotic figures were seen in some cases.
The neoplasms showed a morphologic spectrum that encompassed a group of combined blue nevi with epithelioid melanocytes and other Spitz's nevus characteristics. These epithelioid combined nevi (ECN) fell into three phenotypes with morphologies that most closely paralleled those pictured by Carney and Ferreiro in the Carney complex: the classic or Carney complex pattern (ECN-CC), those that showed overlap with deep penetrating nevus (ECN-DPN), and those that have many dermal Spitz's nevus features, [BLue + SpITZ's nevus; (ECN-BLITZ)I. In six cases, there was such an admixture of features that it was difficult to ascribe them to one of the groups. Nine lesions had associated banal congenital nevus. Follow-up that averaged over 2.5 years (31 months) (range 6-162 months) showed no evidence of malignancy or recurrent disease after excision.
Epithelioid combined nevus is a type of combined nevus with blue nevus and Spitz's nevus features, which may or may not be associated with the Carney complex. It shows morphologic overlap with the epithelioid blue nevus described by Carney (ECN-CC), deep penetrating nevus (ECN-DPN), and blue nevus with intradermal Spitz's (desmoplastic) nevus (ECN-BLITZ). Epithelioid combined nevus is thought to be a fitting nosologic designation for all of these lesions.
MALIGNANT BLUE NEVUS
From the *Department of Dermatology and Clinical Research Institute, National Sapporo Hospital, Sapporo, Japan; and daggerDepartment of Plastic and Reconstructive Surgery and Clinical Research Institute, National Sapporo Hospital, Sapporo, Japan. Reprints: Dr. N. Kato, Chief, Department of Dermatology, National Sapporo Hospital, Kikusui 4-2, Shiroishi-ku, Sapporo 003-0804, Japan
We report a 55-year-old Japanese patient with a malignant blue nevus (MBN) on the scalp. The patient had regional lymph nodes metastases at his first visit, and a distant cutaneous metastatic papule appeared on the back 1 year later despite therapeutic intervention.
Histology of the primary tumor lacked a junctional component and showed a typically biphasic pattern in the degree of pigmentation similar to a cellular blue nevus (BN). One pattern showed nests of less-pigmented, oval-shaped cells with a fairly uniform appearance, and the other pattern showed an aggregation of spindle-shaped cells containing a large amount of melanin pigment intermingled with heavily pigmented melanophages.
Histology of metastatic regional lymph nodes also showed a biphasic proliferative pattern of oval-shaped, pale cells and spindle-shaped, richly pigmented cells. A distant cutaneous metastatic papule on the back showed massive proliferation of atypically large, pale, and oval-shaped melanoma cells with heavily pigmented melanophages just beneath the uninvolved epidermis. These histologic features were different from those of metastatic tumor proliferation from conventional melanoma.
It seems probable that MBN might maintain a different biological and histopathologic character from conventional melanoma when it grows in metastatic sites.
- Atypical Blue Nevus, Malignant Blue Nevus, and Metastasizing Blue Nevus: A Critique in Historical Perspective of Three Concepts Flawed Fatally.
Mones JM, Ackerman AB.
Ackerman Academy of Dermatopathology, New York, New York.
Am J Dermatopathol. 2004 Oct;26(5):407-430. Abstract quote
The same errors that spawned, sustained, and continue to spur the notions of “atypical†Spitz’s nevus, “malignant†Spitz’s nevus, and “metastasizing†Spitz’s nevus are animating of 3 other concepts flawed equally, namely, those of “atypical blue nevus,†“malignant blue nevus,†and “metastasizing blue nevus.â€
Our intention here is to compel to the conclusion, by way of critique in historical perspective, that all neoplasms claimed to be “malignant blue nevus†and “metastasizing blue nevus;†in fact, are melanomas, that all “atypical blue nevi†are either a nevus or a melanoma, and that the trio of curious designations that serve as title of this work are mere evasions transparently from a diagnosis, straightforwardly, of 1 of only 3 possibilities, to wit, “blue nevus,†melanoma, or melanoma in association with a “blue nevus.†Rather than admit uncertainty forthrightly, those who employ circumlocutions that we deplore, such as those under scrutiny here, resort to linguistic maneuvers that, at first blush, seem to have the cachet of scholarship (the jargon used being in keeping with a slew of other well-accepted, but equally bogus diagnoses in [dermato]pathology, among those being “minimal deviation melanoma,†“borderline melanoma,†“nevoid melanoma,†“potentially low-grade melanocytic neoplasm,†and “melanocytic proliferation of uncertain biologic potentialâ€). All those terms and phrases are constructed in a manner designed to make them appear to convey unbridled confidence on the part of a histopathologist, rather than what they are in actuality, that is, a cover abjectly for tentativeness. Scrutiny of the lingo, in very abbreviated form, just catalogued reveals it to be devoid of content utterly. For example, “malignant blue nevus†and “metastasizing blue nevus†not only are contradictions in terms, but they are outrageous violations of principles fundamental to classic Virchowian pathology.
We seek here to debunk that claptrap in the same manner we did “atypical Spitz’s nevus,†“malignant Spitz’s nevus,†and “metastasizing Spitz’s nevus.†It is our hope that readers will consider our arguments worthy because they are logical, will find them convincing because they are irrefutable, and will incorporate the lessons communicated through them so that their own professional life, pathology as a discipline, and, ultimately, patients, are the beneficiaries.
Malignant blue nevus: a case report and molecular analysis.Ariyanayagam-Baksh SM, Baksh FK, Finkelstein SD, Swalsky PA, Abernethy J, Barnes EL.
Am J Dermatopathol 2003 Feb;25(1):21-7 Abstract quote Malignant blue nevus is a rare melanocytic tumor that is described by some authors as a variant of malignant melanoma, whereas others regard it as a distinct entity.
To our knowledge no molecular studies of this tumor have been performed, although the molecular pathogenesis of conventional melanomas has been extensively described. We present a case of malignant blue nevus that developed in a 15-cm congenital blue nevus on the back of a 41-year-old man. Subsequent regional lymph node and lung metastases developed within 1 and 29 months, respectively.
We performed a molecular analysis for loss of heterozygosity on microdissected samples from the spectrum of benign to malignant blue nevus, using a panel of eight genes (MTS1, MXI1, CMM1, p53, NF1, L- hOGG1, and MCC), many of which are commonly associated with conventional melanomas. No loss of heterozygosity was detected, despite informativeness in seven genes.
We suggest that malignant blue nevus may represent a distinct entity with a different molecular pathway to tumorigenesis than that of conventional melanomas.
Am J Surg Pathol 2001;25:316-323
The term ``malignant blue nevus'' refers to a rare and heterogeneous group of melanomas that arise in several clinical settings. This includes melanomas arising in association with a common or cellular blue nevus and those arising de novo and resembling cellular blue nevi.
We reviewed the clinicopathologic features of 10 cases of malignant blue nevi. Six cases proved to be de novo melanoma mimicking cellular blue nevus, but lacking a clear-cut benign component. Two melanomas arose in association with a common blue nevus, and two with a cellular blue nevus. The patients' (5 males, 5 females) ages ranged from 11 to 77 years (average age, 48.1 years). The head and neck was the most common location (6 of 10 patients), with five scalp tumors. Four tumors were located on the trunk; none was located on the extremities. Tumor size ranged from 0.5 to 2.2 cm (average size, 1.1cm). Most lesions had been present for many years before surgical removal. Pigmented dendritic cells were observed in 9 of 10 cases.
The malignant and benign components were easily distinguished in the four cases that arose in association with a common or cellular blue nevus. Abrupt transition between a benign blue nevus and melanoma was readily recognized at scanning magnification as distinctive nodules of epithelioid to spindled cells with a sheet-like growth pattern. In all cases, malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, hyperchromasia, and prominent nucleoli. All 7 patients with follow-up information experienced recurrence (3 patients) or metastasis (4 patients). Three patients died of disease.
Conclusion:
Malignant blue nevus is a heterogeneous group of melanomas that are highly aggressive and often lethal, with a propensity for metastasis to the lymph nodes and lungs.PAUCI-MELANOTIC CELLULAR BLUE NEVUS
- Congenital pauci-melanotic cellular blue nevus.
Busam KJ, Lohmann CM.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Cutan Pathol. 2004 Apr;31(4):312-7. Abstract quote
Unusual or atypical melanocytic nevi can be confused with malignant melanoma. Two patients are presented here with a rare variant of melanocytic nevus. Both were men. One was 39 years old and sought medical attention after trauma of a 'congenital mole'. The other was 24 years old and presented with a history of a slowly growing lesion, which had been known since childhood. In both patients, the lesion occurred on the buttock. They were dermal and superficial subcutaneous nodules measuring 1.5 and 2.3 cm in greatest dimension, respectively.
The tumors were composed of densely cellular fascicles of melanocytes arranged in a lobulated growth pattern. Rare nests of small epithelioid melanocytes were also seen. No melanin pigment was seen on hematoxylin and eosin-stained sections. Focal minimal pigment was noted by Fontana-Masson stain in one case. Involvement of numerous peripheral nerve trunks by fusiform melanocytes was a prominent feature. Rare mitotic figures were seen in melanocytes [1-2 mitoses per 50 high-power fields (HPF)]. The MIB-1 labeling index was low (less than 5% of the lesional cell population was immunopositive).
Both tumors were excised with negative surgical margins. One patient underwent sentinel lymph node biopsy because there was controversy regarding the biologic potential of the lesion. No melanocytic tumor deposits were found in the lymph nodes. On clinical follow up of 11 years and 18 months after complete excision, both patients are alive and well with no evidence of recurrence.
We regard these lesions as congenital monophasic and pauci-melanotic variants of cellular blue nevus. The nevi are presented here to enhance our knowledge of the morphologic spectrum of melanocytic tumors and to help avoid confusion with malignant melanoma.S-100 NEGATIVE BLUE NEVUS Am J Dermatopathol 1999;21:225-228
Applied Immunohistochem 1999;7:255-25938/1358 cases of blue nevi showed minimal or no pigment
S100 and HMB45 was focal/weak or absent in all cases
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES METASTATIC MELANOMA Am J Surg Pathol 1999;23:276-280 Am J Dermatopathol 1996;18:289-295
Cutaneous metastasis of ocular melanoma simulating a blue nevusMalignant melanoma with prominent pigment synthesis: ``animal type'' melanoma Hum Pathol 1999;30:543–50
Densely pigmented lesion with a pushing and highly infiltrative border
The tumor cells tend to aggregate along follicles. High-power inspection reveals densely pigmented tumor cells that resemble melanophages at first glance. Closer inspection reveals all cells to be melanocytes with large nuclei, prominent nucleoli, and variable nuclear-to-cytoplasmic ratios. Bleaching reveals the absence of melanophages and shows all cells to be melanoma cells.
PARAGANGLIOMA-LIKE DERMAL MELANOCYTIC TUMOR
- Paraganglioma-like Dermal Melanocytic Tumor: A Unique Entity Distinct From Cellular Blue Nevus, Clear Cell Sarcoma, and Cutaneous Melanoma.
Deyrup AT, Althof P, Zhou M, Morgan M, Solomon AR, Bridge JA, Weiss SW.
From the *Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA; daggerDepartments of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE; and double daggerDepartment of Pathology, University of South Florida, Tampa, FL.
Am J Surg Pathol. 2004 Dec;28(12):1579-1586. Abstract quote
We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity.
From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy.
Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation.
Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.
PROGNOSIS AND TREATMENT CHARACTERIZATION RECURRENCE Persistent and recurrent blue nevi.
Harvell JD, White WL.
Department of Pathology, Stanford University Medical Center, California, USA.
Am J Dermatopathol 1999 Dec;21(6):506-17 Abstract quote
Persistence of common melanocytic nevi has been fairly well characterized, clinically and histologically. In contrast, persistence of blue nevi has been reported infrequently. To define this entity better, nine cases of biologically persistent and clinically recurrent blue nevi are described.
The persistent lesions in four cases were spindle-fascicular blue nevi; one showed senescent or "ancient" change and one had additional deep penetrating/epithelioid blue nevus features with atypical changes worrisome for malignancy. These changes included increased cellularity, cellular pleomorphism, mitotic figures, and a lymphocytic infiltrate. Three were biphasic dendritic-sclerotic/spindle-fascicular blue nevi, one of which had atypical changes. One case was a dendritic-sclerotic ("common") blue nevus. The original histology in one case was unavailable, but the recurrence was a combined blue nevus. The interval from initial biopsy to biopsy of the recurrent lesion was often longer (mean 2.7 years) for recurrent blue nevi than for recurrent common compound or intradermal melanocytic nevi. In addition, in contrast to recurrent common melanocytic nevi, the recurrence, in at least one case, extended beyond the scar of the original excision.
These cases demonstrated that blue nevi of all histiotypes and combinations are capable of persistence with clinical recurrence. The persistence usually was histologically similar to the original, but in some cases was more "cellular" because, for the most part, the excisions of the persistent lesion revealed a deeper spindle-fascicular ("cellular") component not evident in the original superficial biopsy. In two cases, the original blue nevus appeared completely banal, but the persistent/recurrent lesions were histologically distinct and demonstrated atypical histologic features. Yet, follow-up (average 3.7 years) supports benign biology. Clinical recurrence is often associated with malignant transformation in blue nevus, but this series demonstrates that malignant tumor progression is not necessarily the case.
In the absence of necrosis en mass, marked cytologic atypia, and frequent mitotic figures, the described atypical morphologic parameters in previously biopsied small blue nevi are probably reactive and "pseudomalignant." Awareness of this potential change may avoid diagnostic and prognostic errors.
Metastasis J Cutan Pathol 1993;20:459-464
Pathol Case Reviews 1999;4:97-102There are rare cases of melanoma arising with a blue nevus
Melanoma Associated With Blue Nevus and Melanoma Mimicking Cellular Blue Nevus A Clinicopathologic Study of 10 Cases on the Spectrum of So-Called Malignant Blue Nevus Am J Surg Pathol 2001;25:316-323 Abstract quote
The term ``malignant blue nevus'' refers to a rare and heterogeneous group of melanomas that arise in several clinical settings. This includes melanomas arising in association with a common or cellular blue nevus and those arising de novo and resembling cellular blue nevi. We reviewed the clinicopathologic features of 10 cases of malignant blue nevi. Six cases proved to be de novo melanoma mimicking cellular blue nevus, but lacking a clear-cut benign component. Two melanomas arose in association with a common blue nevus, and two with a cellular blue nevus. The patients' (5 males, 5 females) ages ranged from 11 to 77 years (average age, 48.1 years). The head and neck was the most common location (6 of 10 patients), with five scalp tumors. Four tumors were located on the trunk; none was located on the extremities. Tumor size ranged from 0.5 to 2.2 cm (average size, 1.1cm). Most lesions had been present for many years before surgical removal.
Pigmented dendritic cells were observed in 9 of 10 cases. The malignant and benign components were easily distinguished in the four cases that arose in association with a common or cellular blue nevus. Abrupt transition between a benign blue nevus and melanoma was readily recognized at scanning magnification as distinctive nodules of epithelioid to spindled cells with a sheet-like growth pattern. In all cases, malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, hyperchromasia, and prominent nucleoli.
Two major histologic patterns. The first is a sheet-like growth of malignant epithelioid or spindled cells in association with common or cellular blue nevus. The second lacks a malignant component yet mimics benign cellular blue nevus at low-power. Closer examination demonstrates some of the following features: infiltrative borders, distinctive expansile nodules, pleomorphism, prominent nucleoli, mitoses, and necrosis. Rapid growth of a clinical blue nevus, large size, or unusual gross morphology such as multinodularity should be cause for alarm and elicit prompt excision to evaluate for malignant change. An excision is preferable because this form of biopsy is less likely to cause diagnostic error as a result of sampling bias. Furthermore, the pathologist should generously sample and carefully examine all potential cellular blue nevi for evidence of malignant change. In particular, care is advised in examining blue nevi of the scalp in older individuals.
All 7 patients with follow-up information experienced recurrence (3 patients) or metastasis (4 patients). Three patients died of disease.
Conclusion:
Malignant blue nevus is a heterogeneous group of melanomas that are highly aggressive and often lethal, with a propensity for metastasis to the lymph nodes and lungs.Treatment Simple excision Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Dendritic melanocytes-These are a variant of melanocytes that have a spindled appearance. Usually the cells are heavily laden with melanin pigment. There is no sinister connotation.
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