692 INVESTIGATIVE REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Differential Clinicopathological Features in Spontaneous Regression of Melanomas and Melanocytic Naevi
José M. MARTÍN 1, 2, Isabel PINAZO 1, 2, Esperanza JORDÁ 1, 2 and Carlos MONTEAGUDO 2, 3
1
Department of Dermatology, 3 Department of Pathology, Hospital Clínico Universitario, and 2 School of Medicine, University of Valencia, Valencia, Spain
The aim of this study was to determine the clinical, histological and / or immunohistochemical features that enable differential diagnosis of regression of melanocytic naevi from regression of melanomas. All melanocytic neoplasms with histologically-confirmed regression diagnosed in our hospital between 2002 and 2009 were reviewed retrospectively. Lamellar and delicate fibrosis were associated with melanocytic naevi( p < 0.0001 and p = 0.021, respectively). Compact fibrosis, high vessel density and higher number of granzyme B + lymphocytes were associated with malignant melanoma( p = 0.011, p = 0.005 and p = 0.013, respectively). Density of inflammatory infiltrate( p = 0.016), vascular proliferation( p = 0.005), epidermal atrophy( p = 0.009), rate of apoptosis( p = 0.046) and granzyme B immunoreactivity( p = 0.013) was more common in severe – dysplastic naevi and melanomas than in the remaining melanocytic naevi. Logistic regression demonstrates that 5 variables( age, lamellar fibrosis, melanophages, vessel density, and granzyme B immunostaining) would serve to classify appropriately 87 % of melanomas among melanocytic lesions with complete regression.
Key words: melanocytic naevi; melanoma; regression. Accepted Feb 20, 2017; Epub ahead of print Feb 22, 2017 Acta Derm Venereol 2017; 97: 692 – 697.
Corr: José M. Martín, Servicio de Dermatología, Hospital Clínico Universitario, Avda. Blasco Ibáñez 17, ES-46010 Valencia, Spain. E-mail: Martin. josemaria @ gmail. com
Melanoma and melanocytic naevi are among the group of tumours most able to stimulate an immune response. In fact, regression of melanoma is 6 times more frequent than in other malignant neoplasms( 1), and while histologically-confirmed complete regression of melanomas is exceptional, partial regression occurs in 10 – 35 % of cases( 2).
Several mechanisms are potentially involved in the induction of regression, although an immune mechanism seems to be most consistently associated with this process( 2 – 4).
The essential feature of a melanoma undergoing spontaneous regression is the replacement of tumour cells by a fibrous stroma with varying degrees of inflammation and new blood vessel formation, as well as varying numbers of melanophages, similar to the changes seen in regression of melanocytic naevi( 2, 5, 6). From an exclusively histological perspective, it is very difficult to determine the malignant or benign nature of a lesion after complete regression and, in most cases, only the detection of metastasis during clinical follow-up allows this distinction to be made with certainty.
This study attempted to identify clinical, histological and immunohistochemical features that could be helpful in differentiating regression of benign melanocytic lesions from that of melanomas.
MATERIALS AND METHODS
This study retrospectively evaluated a variety of clinical, histopathological and immunohistological characteristics of all melanocytic neoplasms with histological regression diagnosed in our hospital over an 8-year period( from 1 January 2002 to 31 December 2009). The specimens were identified from a histological database using the keywords“ regression”,“ melanocytic naevi” and“ melanoma”.
Regression was accepted when replacement of tumour cells by a fibrous stroma with varying degrees of inflammation, as well as new blood vessel formation and varying numbers of melanophages, were present( Fig. 1). None of the lesions evaluated were associated with previous inflammatory or infectious reactions, or previous treatments that could justify the development of regression.
The study included a total of 163 tumour samples: 39 nondysplastic melanocytic naevi, 77 dysplastic naevi, and 47 primary cutaneous melanomas( 31 superficial spreading melanomas, 11 lentigo maligna, 2 acral lentiginous melanomas, 2 nodular melanomas, and 1 unclassifiable melanoma).
All samples were fixed in 4 % neutral formaldehyde. After embedding in paraffin, 3- µ m thick sections were cut and stained with haematoxylin and eosin. To evaluate immunohistochemistry, 6 tissue microarrays( TMA) were built using the MTA-1( Manual Tissue Arrayer, Beecher Instruments, Inc., Sun Prairie, WI, USA). The most representative areas of each slide were selected for evaluation, especially those with prominent inflammatory infiltrate, and assembled in a new paraffin block.
The following variables were recorded for analysis:( i) Clinical data: patient age and sex, location of lesion;( ii) Histological data: diagnosis( melanoma, severe-dysplastic naevi, mild-dysplastic naevi, non-dysplastic naevi); fibrosis: extent( slight, moderate, extensive), type( lamellar, compact, delicate, florid or indeterminate), and location( subepidermal accentuation); mononuclear inflammatory infiltrate: density, type( patched or diffuse) and location( intratumoural or peritumoural); melanophages( density); blood vessel formation( density); tumour cell apoptosis( none, slight, intense); melanocytic loss,( slight, moderate, extensive, total); and epidermal atrophy( present or absent); and( iii) Immunohistochemical data: immunostaining of lymphocytes was performed with 6 commercial antibodies to CD4( clone 1F6; Novocastra), CD8( clone 1A5; Novocastra), CD25( clone 4C9; Novocastra), FoxP3( clone 236A / E7; Abcam), and granzyme B( clone GrB-7; Dako). doi: 10.2340 / 00015555-2641 Acta Derm Venereol 2017; 97: 692 – 697
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.