Table 2: Summary of the specificity of immunohistochemical profiles of BPDCN vs. myeloid leukemia cutis BPDCN %
Myeloid leukemia cutis %
CD123
75-100 82-100 50-100
9-17 9-17
TCL1
BDCA2/CD303
3 4
CD2AP
45-95
BCL11A
83-100 90-100 80-100 75-100
25 78
CLA
CD4
9-61
CD56
52
MPO
0
30-67
Table 2: Summary of the specificity of immunohistochemical profiles of BPDCN versus myeloid leukemia cutis. 6,14,15,17,21-23
such as CD123, TCL-1, BDCA2 (CD303) without expression of T-cell, B-cell, and NK-cell or myelomonocytic lineage specific markers, although expression of CD2 and CD7 is not an uncommon finding. 4 CD4-negative cases 9,14,15 and CD56-negative 8-10,15 cases have rarely been reported in case reports. Despite CD123 and TCL1 being generally positive in BPDCN, CD123-negative and TCL1-negative cases were reported. 8,14,15,17 BPDCN also expressed BDCA2, CD2AP, BCL11A (B-cell lymphoma/leukemia 11A), and CLA (cutaneous lymphocyte antigen). 9,10,14,15 TDT-positive and HLA-DR-positive cases were not uncommon. 9-12,15 TDT was expressed in 14%-64% of cases. 9,10,15 Interestingly, our case showed that TdT was expressed in bone marrow by flow cytometry but not expressed in skin by IHC. Khoury et al. demonstrated that the level of TdT expression by IHC was higher in lymph node than in skin. 18 These findings may suggest different patterns of TdT expression in various in- volved tissues and potential association with various stages of the disease. CD2 was aberrantly expressed in 33%-52% of cases. 8,9,15 CD5 expression was extremely rare and reported in a single case on bone marrow specimen. 19 We speculate that the partial expression of CD5 in our case is either an aberrant expression or may represent neoplastic PDCs un- dergoing cell fate conversion to lymphoid phenotype. CD7 was expressed in a few cases, occasionally in the form of subset or focal positivity. 10,11 BPDCN was generally nega- tive for CD3, CD20, CD34, CD117, myeloperoxidase, and EBV. 8-10,14,15 Rare cases were reported to express cytoplasmic CD3. 11,18,20 CD34 and CD117 were expressed in rare cases (Adams et al., 2009; Chen et al., 2011). CD33 is generally negative, 9 but rare CD33-positive cases were reported. 8,13 CD68 was expressed in quite a few cases, and in some cases, in the formof cytoplasmic dots. 8-10 In three case series, CD68 positivity was 53%-86%. 8,9,15 Focal positivity of S100 was reported in three-fourths of pediatric cases (75%) and may represent a favorable prognostic factor, 10 whereas S100 was expressed in 17%-25% of adult patients. 3,8 Hashikawa et al. showed 8 out of 15 (53%) skin biopsy specimen-expressed
CXCL12, which was associated with high leukemic change and poor prognosis. 8 EBV antigens/EBV-encoded nuclear RNA (EBER) and T-cell/B-cell gene rearrangement were consistently negative. 8-10 The Specificity of PDC-Associated Antigens The diagnosis of BPDCN is largely based on the PDC- associated antigens such as CD123, TCL1, BDCA2, and CLA, but most of these markers have been shown to be expressed by other lesions as well. The specificity of PDC-associated antigens is summarized in Table 2. 6,14,15,17,21-23 Benet et al. showed that CD123 and CD303 (BDCA2) were expressed in 11 out of 123 (9%) and 4 out of 124 (3%) myeloid leukemia cutis (LC) cases, respectively. 21 Vitte et al. reported that, in 42 chronic myelomonocytic leukemia (CMML) patients with skin involvement, 45%-50% of the skin lesions expressed CD123, CD303 (BDCA2), and TCL1, indicating the associa- tion of BPDCN with myelodysplastic/myeloproliferative neoplasms such as CMML. 23 Cronin et al. revealed that CD123 was expressed in 4 out of 23 (17%) of myeloid leuke- mia cutis (LC) and 10 out of 12 (83%) of BPDCN cases, while TCL1 was expressed in 2 out of 23 (9%) of LC and 9 out of 11 (82%) of BPDCN cases. 17 In a study by Petrella et al. of 29 formerly called agranular CD4+CD56+ hematodermic neo- plasms (HN) cases and 18 myelomonocytic leukemia cutis (LC) cases, TCL1 was expressed in 26 out of 29 (90%) of HN and 3 out of 18 (17%) LC cases, while CLAwas expressed in 26 out of 29 (90%) of HN and 14 out of 18 (78%) of LC cases. 22 CLA as a skin lymphocyte homing molecule is rather non- specific for BPDCN, and has been reported to be universally expressed in myeloid LC and cutaneous T-cell lymphoma (Campbell et al., 2010; Sachdev et al., 2012). Marafioti et al. showed that CD2AP was expressed in 35 out of 37 (95%) of formerly called CD4+CD56+HN and 1/24 (4%) of LC cases, but not expressed in 24 CML, CMML, B-ALL, and T-ALL cases. In contrast, BCL11A was expressed in 39 out of 39 (100%) HN, 6 out of 24 (25%) LC, 1 out of 7 (14%) CML, 3 out of 5 (60%) CMML, 7 out of 7 (100%) B-ALL, and 4 out
J La State Med Soc VOL 166 January/February 2014 7
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