Slodkowska Elzbieta A, Cribier Bernard, Peltre Bernard, Jones David M, Carlson J Andrew
Division of Dermatology and Dermatopathology, Department of Pathology, Albany Medical College, NY 12208, USA.
Am J Dermatopathol. 2010 Aug;32(6):557-64. doi: 10.1097/DAD.0b013e3181ca65e2.
Carcinoma-associated calcifications (Ca(2+)) are a common phenomenon. In the skin, basal cell carcinomas (BCC) can be associated with Ca(2+).
To examine the prevalence, characteristics, and clinicopathologic correlations of BCC associated with Ca(2+).
Eighty-three BCC with Ca(2+) were retrieved, 27 (11.1%) of which were identified from a review of 243 consecutive BCC. Ca(2+) were classified into 4 types: type 1, Ca(2+) within BCC epithelium; type 2, Ca(2+) in BCC keratocysts; type 3, BCC tumor necrosis with Ca(2+); and type 4, free Ca(2+) adjacent to BCC. Clinical and pathologic features were assessed and compared with BCC without Ca(2+). Expression of hair-associated proteins (hair keratins (K31, K32, and K35) and matrical transcription factors (LEF1, HOXC13, and β-catenin) were examined in a subset of BCC with Ca(2+) and compared with matched controls without Ca(2+).
Compared with BCC without Ca(2+), BCC with Ca(2+) were significantly more likely to show a nodular keratinizing phenotype with keratocyst formation, background solar elastosis, active regression, and areas of tumor necrosis (all P ≤ 0.03). Comparing all BCC, high-risk BCC (mostly infiltrative) had significantly higher frequency of Ca(2+) than low-risk (mostly nodular) BCC (44% vs. 25%; P = 0.009). The median and mean number of Ca(2+) deposits per specimen were 2 and 3 ± 4, range 1-30. In decreasing frequency, type 2 Ca(2+) (58%), type 4 (53%), type 3 (14%), and type 1 (10%) were found. In 9 cases (11%), type 2 and type 4 Ca(2+) were linearly arranged, ostensibly after a follicular or eccrine duct tract. In 5 cases (6%), initial histologic sections showed type 4 dermal Ca(2+) without evidence of BCC; level sections revealed BCC in the adjacent tissue. Neither BCC with nor BCC without Ca(2+) showed evidence of matrical differentiation by immunophenotypic analysis.
A minority of BCC exhibits Ca(2+) that are associated with BCC-related keratin and/or necrosis. Like other follicular-derived tumors (trichilemmal cyst, pilomatricoma, and trichoepithelioma), BCC produce keratins that are ostensibly predisposed to calcification but are not related to matrical differentiation (mature hair keratin formation). Either due to transtumor elimination or due to tumor regression, Ca(2+) are frequently found free in solar elastotic or fibrotic dermis: a histologic clue in sun-damaged skin to the presence of BCC in the surrounding dermis.
癌相关钙化（Ca(2+)）是一种常见现象。在皮肤中，基底细胞癌（BCC）可伴有Ca(2+)。
研究伴有Ca(2+)的BCC的患病率、特征及临床病理相关性。
收集83例伴有Ca(2+)的BCC，其中27例（11.1%）是从243例连续的BCC回顾性研究中识别出的。Ca(2+)分为4种类型：1型，BCC上皮内的Ca(2+)；2型，BCC角质囊肿内的Ca(2+)；3型，伴有Ca(2+)的BCC肿瘤坏死；4型，BCC邻近的游离Ca(2+)。评估临床和病理特征，并与不伴有Ca(2+)的BCC进行比较。在一部分伴有Ca(2+) 的BCC中检测毛发相关蛋白（毛发角蛋白（K31、K32和K35）和基质转录因子（LEF1、HOXC13和β-连环蛋白）的表达，并与匹配的不伴有Ca(2+)的对照进行比较。
与不伴有Ca(2+)的BCC相比，伴有Ca(2+)的BCC更易表现为结节性角化型伴角质囊肿形成、背景性日光性弹力组织变性、活动性消退及肿瘤坏死区域（所有P≤0.03）。在所有BCC中，高危BCC（大多为浸润性）的Ca(2+)频率显著高于低危BCC（大多为结节性）（44%对25%；P = 0.009）。每个标本中Ca(2+)沉积的中位数和平均数分别为2和3±4，范围为1 - 30。按出现频率递减，发现2型Ca(2+)（58%）、4型（53%）、3型（14%）和1型（10%）。在9例（11%）中，2型和4型Ca(2+)呈线性排列，表面上沿毛囊或小汗腺导管走行。在5例（6%）中，最初的组织学切片显示为4型真皮Ca(2+)，无BCC证据；连续切片显示邻近组织中有BCC。通过免疫表型分析，伴有或不伴有Ca(2+)的BCC均未显示基质分化的证据。
少数BCC表现出与BCC相关角蛋白和/或坏死相关的Ca(2+)。与其他毛囊源性肿瘤（外毛根鞘囊肿、毛母质瘤和毛发上皮瘤）一样，BCC产生的角蛋白表面上易于钙化，但与基质分化（成熟毛发角蛋白形成）无关。由于肿瘤内清除或肿瘤消退，Ca(2+)常游离于日光性弹力组织变性或纤维化的真皮中：这是日光损伤皮肤中周围真皮存在BCC的组织学线索。
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