Review Article

Density of Langerhans Cells in Nonmelanoma Skin Cancers: A Systematic Review

Table 2

The summary of the studies in which the number of LCs was measured in SCC.

First author, dateNo of casesThe purpose(s) of the studyLangerhans cells immunostaining measurement methodMeasurement locationCell numbers

Korenberg, 1987 [26]12Quantification of LCs in inflamed and noninflamed keratoakanthoma and SCCAnti-S100 antibody
Calculation in 4 HPFs
IntratumouralInflamed SCC: 2.6 (range 0-8) or 3.2 (0-10)
Noninflamed SCC: 2.0 (0-8) or 3.0 (0-7)
Tucci, 1998, [29]5Analysis of relationship between transformation of keratinocytes and markers of oncogenesisAnti-CD1a antibody
Calculation per 0.01 mm2 in 10 fields of vision
Intratumoural
Wei, 1998 [16]36Analysis of association of S100+ cells presence in SCC and presence of metastatesPolyclonal anti-S100 antibody
Three cases with/with no metastasis stained with anti-CD1a antibody
Calculation per mm2
Intra- and peritumouralPT: mean (range: 0-1243)
When stained with anti-CD1a 57% of S100+ cells were identified
IT: mean (range: 0-893)
No diffrences when stained with CD1a
Berhane, 2001 [50]19Analysis of progression of AK to SSCAnti-CD1 antibodies
Calculation by the number per mm2
IntratumouralCD1:
Ko, 2006 [51]10Comparison of BCL-2 and CD1a staining in various skin pathologiesAnti-CD1a antibody
Calculation in 2 HPFs of 0.25 mm2
Intratumoural
Rotsztejn, 2006 [30]5Analysis of LC number in vulvar SCCAnti-CD1a antibody
Calculation per 10 HPFs
Intratumoural1.0-1.7 (range 0.0-4.0)
Galan, 2007 [31]12Comparison of LC in PEH vs SCCAnti-CD1a antibodies
Calculation in two different 0.5 mm2 fields of vision
Epidermis overlying the tumours7.5/0.5 mm2
Rotsztejn, 2007 [52]13Analysis of LC number in vulvar SCCAnti-CD1a antibody
Calculation per 10 HPFs
Intratumoural (range 0.0-2.0)
Bluth, 2009 [52]10Analysis of immune microenvironment and function of tumour myeloid DCsAnti-CD1a and anti-CD207 antibodies
Calculation based on computer-assisted manual counting of positive cells
Extrapolation to unit area (100,000 μm2)
Intra- and peritumouralIT: CD1a: 7.1/100,000 μm2, (median)
CD207: 7.0/100,000 μm2 (median)
PT: CD1a: 0.0/100,000 μm2, (median)
CD207: 0.0100,000 μm2 (median)
Takahara, 2009 [34]15Analysis of correlation between tumour cell proliferation and epidermal LCAnti-CD1a antibody
Calculation per three HPFs
Intratumoural
Sandvik, 2014 [27]30 (15 RTR, 15 control)Quantification of cells in surrounding of SCC and LC in epithelial tumour nests
Comparison with IC patients
Anti-CD207 antibody
Calculation among the keratinocytes in the tumour in average 8 random places
Then extrapolated to number per mm2
Intra- and peritumouralIntratumoural:
-IS patients: median 30/mm2
-IC patients: median 35/mm2
Gomes, 2015 [53]21Comparison of density and distribution in epithelium and IDC of LC in AC and SCCAnti-CD1a antibody
Calculation in seven fields of vision
Then extrapolated to 1 mm2
Epithelium and connective tissue of the tumourEpithelium:
Connective tissue (interstitial dendritic cells):

AC: actinic cheilitis; AK: actinic keratosis; CD: cluster of differentiation; DC: dendritic cells; HPF: high-power fields; IC: immunocompetent; IS: immunosuppressive; IT: intratumoural; LC: Langerhans cells; PEH: pseudoepitheliomatous hyperplasia; PT: peritumoural; RTR: renal transplant recipient; SCC: squamous cell carcinoma.