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 .