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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC’s inaugural meetings are presented herein.

Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non-immune checkpoint inhibitor (non-ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited.A comprehensive review was conducted on dermatologic toxicities associated with different classes of non-ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta-analyses; and case series/reports.Dermatologic toxicities were associated with several types of non-ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non-ICI mAbs. Immunobullous reactions were rare and a subset of non-ICI mAbs were associated with the development of vitiligo cAEs.Dermatologic toxicities of non-ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non-ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

The immunohistochemical (IHC) marker PReferentially expressed Antigen in MElanoma (PRAME) has shown promise in the diagnosis of melanocytic lesions. A few studies have investigated PRAME IHC expression in acral melanomas, but PRAME expression in subungual melanomas is largely unknown. We evaluated the utility of PRAME IHC expression in distinguishing subungual melanomas (SUM) and non-subungual acral melanomas (AM) from acral nevi (AN).Twenty-two SUM, 20 AM, and 14 AN were identified. IHC studies were performed using an anti-PRAME antibody. The percentage of lesional cells with PRAME expression was recorded and categorized as follows: 0%, 0; 1%-25%, 1+; 26%-50%, 2+; 51%-75%, 3+; and75%, 4+. Patient demographics and other relevant clinicopathologic parameters were recorded.Diffuse (4+) PRAME IHC expression was identified in 55% (12/22) SUM and 70% (14/20) AM, respectively. Any PRAME expression (1+ to 4+) was identified in 73% (16/22) SUMs and 95% (19/20) AM, respectively. One of 14 (7%) AN exhibited PRAME expression; interestingly, the pattern of expression was diffuse.In our study, PRAME IHC expression was useful in identifying AM, including SUM. However, there are exceptions of PRAME-negative melanomas and PRAME-positive nevi.

Merkel cell carcinoma (MCC) is an aggressive, highly metastatic, cutaneous neuroendocrine malignancy with poor prognosis. Here, we describe a MCC excision specimen with a rare case of tumor-associated amyloid deposition in the absence of residual tumor cells. A 72-year-old man presented with a lesion of 5-6 months' duration on his left elbow, clinically thought to be a ganglion cyst. The biopsy specimen revealed a Stage IIA MCC with classic histomorphologic and immunophenotypic findings, with tumor extending to the tissue edges. The patient underwent wide local excision with negative margins and a negative sentinel lymph node biopsy. Although the patient did not receive any presurgical chemotherapy, immunotherapy, or targeted therapy, the re-excision specimen showed only amphophilic, feathery deposits that were salmon-pink with Congo red stain and further confirmed as amyloid by electron microscopy; there were no residual carcinoma cells. Amyloid deposition in MCC has been described in rare case reports. Our case was extraordinary in that there was only amyloid deposition and an associated granulomatous reaction, without identifiable MCC cells. This case demonstrates that amyloid deposition may be evidence of a prior MCC at the site of a prior procedure and may warrant careful evaluation for residual MCC.

Context.— The recently identified immunohistochemical marker TRPS1 is highly sensitive and specific for invasive breast carcinoma, especially triple-negative breast carcinoma. However, TRPS1 expression in special morphologic subtypes of breast cancer is unclear. Objective.— To investigate the expression of TRPS1 in invasive breast cancer with apocrine differentiation, in comparison to the expression of GATA3. Design.— A total of 52 invasive breast carcinomas with apocrine differentiation, comprising 41 triple-negative breast carcinomas and 11 estrogen receptor (ER) and progesterone receptor (PR)–negative, human epidermal growth factor receptor 2 (HER2)–positive cases, along with 11 triple-negative breast carcinomas without apocrine differentiation, were evaluated for TRPS1 and GATA3 expression by immunohistochemistry. All tumors were diffusely positive (>90%) for androgen receptor (AR). Results.— Triple-negative breast carcinoma with apocrine differentiation had positive TRPS1 expression in 12% of cases (5 of 41), whereas GATA3 was positive in all cases. Similarly, HER2+/ER− invasive breast carcinoma with apocrine differentiation showed positive TRPS1 in 18% of cases (2 of 11), whereas GATA3 was positive in all cases. In contrast, triple-negative breast carcinoma with strong AR expression but without apocrine differentiation showed both TRPS1 and GATA3 expression in 100% (11 of 11) of cases. Conclusions.— Most ER−/PR−/AR+ invasive breast carcinomas with apocrine differentiation are TRPS1 negative and GATA3 positive, regardless of HER2 status. Therefore, TRPS1 negativity does not exclude breast origin in tumors with apocrine differentiation. A panel of TRPS1 and GATA3 immunostains can be helpful when the tissue origin of such tumors is clinically relevant.

Supplemental Figure 1. Correlation between dermal mitotic rate and patient survival. Kaplan-Meier estimate of (A) overall survival and (B) disease-specific survival based on dermal mitotic rate (mitotic figures/mm2). Supplemental Figure 2. Derivation of proposed T-category for Primary Vulvar Melanoma. (A, B, C) We first assigned patients with PVM to a T-category according to the AJCC for PCM (7th Edition). (A) Shows the AJCC schema and the number of patients assigned to each category. (B) Kaplan Meier DSS curves for patients stratified by AJCC T-categories demonstrate robust prognostic differences for patients with PVM and pT1 and to an extent pT2 disease from those with pT3 and pT4 disease, but less robust stratification among those patients with PVMs {less than or equal to}2.00 mm; pT1 versus pT2 (isolated in C) or >2.0 mm; pT3 and pT4. (D, E, F) Because both tumor thickness and mitotic rate were independent prognostic factors for DSS and because mitotic rate showed a natural prognostic separation at 2 mitotic figures/mm2 (as shown in Figure 1D), we first asked whether a T-category according to the conventional AJCC cut-offs ({less than or equal to}1.0, 1.01-2.0, 2.01-4.0 and >4.0 mm) subsequently modified by mitotic rate (a: 2.0 mm (pT3 and pT4) had a short DSS independent of mitotic rate. More importantly, among patients with a tumor thickness {less than or equal to}2.0 mm (pT1 or pT2), only those with mitotic rate {greater than or equal to}2/mm2 had a short DSS, which was essentially superimposable with patients with pT3 and pT4 PVM in this schema. (F) Kaplan-Meier survival curve for patients with pT1 and pT2 PVMs show striking differences in survival according to mitotic rate (

Supplemental Table 1. Summary of the clinical and histopathologic characteristics of Merkel cell carcinoma patients. Supplemental Table 2. Summary of antibodies used in this study. Supplemental Table 3. Correlation between tumor associated immune infiltrate and co-localized expression of CD31 and B7-H3 in Primary MCCs.

Kaplan-Meier estimate of (A) overall survival and (B) disease-specific survival based on dermal mitotic rate (mitotic figures/mm2).

Purpose:In patients with cutaneous melanoma, metastasis in a nonsentinel lymph node (non-SLN) is a strong independent adverse prognostic factor. However, patients with a tumor-involved SLN no longer routinely undergo completion lymph node dissection (CLND). We hypothesized that SLN tumor burden may predict non-SLN tumor burden.Experimental Design:We compared tumor burden parameters between SLN and non-SLN in patients with cutaneous melanoma who underwent SLN biopsy with a positive SLN during 2003 to 2008 at The University of Texas MD Anderson Cancer Center.Results:We identified 336 eligible patients with a positive SLN. Of these, 308 (92%) underwent CLND, and 35 (10%) had non-SLN metastasis. The median follow-up time was 6.0 years. For patients with maximum diameter of tumor in the SLN ≤2.0 mm, >2.0–5.0 mm, and >5.0 mm, non-SLN metastasis was detected in 5 of 200 patients (3%), 10 of 63 patients (16%), and 20 of 57 patients (35%), and the mean maximum diameters of the non-SLN tumor deposits were 0.09, 1.56, and 2.71 mm, respectively (P < 0.0001). The percentage of patients with both subcapsular and intraparenchymal non-SLN tumor was higher for patients with SLN tumor in both locations than for patients with SLN tumor in only one location (P < 0.0001). Extranodal extension in a non-SLN was more common in patients with extranodal extension in an SLN (P = 0.003).Conclusions:In patients with cutaneous melanoma who undergo CLND, SLN tumor burden predicts non-SLN tumor burden. SLN tumor burden parameters provide accurate prognostic stratification independent of non-SLN status and should be considered for incorporation into future staging systems and integrated risk models.

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Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM.Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS).Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort.Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.

Supplemental Figure 1. Dynamic range of co-localized expression of CD31 and B7-H3 in primary Merkel cell carcinoma. Each CD31+ and B7-H3+ cell centroid was tabulated as a series of (X, Y) coordinates (cell centroids). The frequency of their respective overlap for each of the 52 primary MCCs was calculated within a given distance as indicated: blue boxes show G-function colocalization index applying a 1 pixel (1.57 �m) minimum distance of overlapped expression as our cutoff, and green boxes show G-function colocalization index applying a 2 pixel (3.14 �m) minimum distance of overlapped expression as our cutoff.

Purpose:Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy whose pathogenesis and prognosis are related to the integrity of the host immune system. Despite promising clinical responses to immune-checkpoint blockade, response and resistance remain unpredictable, underscoring a critical need to delineate novel prognostic biomarkers and/or therapeutic targets for this disease.Experimental Design: Expression of immune-regulatory markers (PD-L2, B7-H3, B7-H4, IDO-1, ICOS, TIM3, LAG3, VISTA, and OX-40) was assessed using singlet chromogenic IHC in 10 primary MCCs. Multiplex immunofluorescence quantified CD31 and B7-H3 expression in 52 primary and 25 metastatic MCCs. B7-H3 and CD31 expressions were tabulated as a series of independent (X,Y) cell centroids. A spatial G-function, calculated based on the distribution of distances of B7-H3+ (X,Y) cell centroids around the CD31+ (X,Y) cell centroids, was used to estimate a colocalization index equivalent to the percentage of CD31-positive cell centroids that overlap with a B7-H3–positive cell centroid.Results:Primary and metastatic MCCs exhibit a dynamic range of colocalized CD31 and B7-H3 expression. Increasing colocalized expression of B7-H3 with CD31 significantly associated with increased tumor size (P = 0.0060), greater depth of invasion (P = 0.0110), presence of lymphovascular invasion (P = 0.0453), and invasion beyond skin (P = 0.0428) in primary MCC. Consistent with these findings, increasing colocalized expression of B7-H3 and CD31 correlated with increasing vascular density in primary MCC, but not metastatic MCC.Conclusions:Our results demonstrate that colocalized expression of B7-H3/CD31 is a poor prognostic indicator and suggest therapies targeting B7-H3 may represent an effective approach to augmenting immune-activating therapies for MCC.

Purpose: Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. Because programmed death ligand-1 (PD-L1) is frequently expressed in MCC, immune checkpoint blockade has been leveraged as treatment for metastatic disease. There is therefore a critical need to understand the relationships between MCPyV status, immune profiles, and patient outcomes.Experimental Design: IHC for CD3, CD8, PD-1, PD-L1, and MCPyV T-antigen (to determine MCPyV status) was performed on 62 primary MCCs with annotated clinical outcomes. Automated image analysis quantified immune cell density (positive cells/mm2) at discrete geographic locations (tumor periphery, center, and hotspot). T-cell receptor sequencing (TCRseq) was performed in a subset of MCCs.Results: No histopathologic variable associated with overall survival (OS) or disease-specific survival (DSS), whereas higher CD3+ (P = 0.004) and CD8+ (P = 0.037) T-cell density at the tumor periphery associated with improved OS. Higher CD8+ T-cell density at the tumor periphery associated with improved DSS (P = 0.049). Stratifying MCCs according to MCPyV status, higher CD3+ (P = 0.026) and CD8+ (P = 0.015) T-cell density at the tumor periphery associated with improved OS for MCPyV+ but not MCPyV− MCC. TCRseq revealed clonal overlap among MCPyV+ samples, suggesting an antigen-specific response against a unifying antigen.Conclusions: These findings establish the tumor-associated immune infiltrate at the tumor periphery as a robust prognostic indicator in MCC and provide a mechanistic rationale to further examine whether the immune infiltrate at the tumor periphery is relevant as a biomarker for response in ongoing and future checkpoint inhibitor trials in MCC. Clin Cancer Res; 22(22); 5553–63. ©2016 AACR.

Table S1A. Relationship between RFS and MSS, and size of tumor deposit in the SLN using the cut-off values of < 0.1 mm, 0.1-1.0 mm, and > 1.0 mm (univariate analysis); Table S1B. Relationship between SLN and non-SLN tumor burden using the cut-off values of < 0.1 mm, 0.1-1.0 mm, and > 1.0 mm (univariate analysis)

Supplemental Figure 2. Correlation between B7-H3/CD31 G-function co-localization index in MCPyV-positive MCCs. Plots showing the correlation B7-H3/CD31 G-function co-localization index for each primary MCPyV-positive MCC plotted against tumor size (A), depth of invasion (B), invasion beyond skin (C) and metastasis beyond SLN (D). G-function calculated according to a 1 pixel (1.57 �m) radius.

(A) Kaplan-Meier plot for age and disease specific survival applying a cut off of 71y. (B) Kaplan-Meier plot for sex and disease specific survival. (C) Kaplan-Meier plot for MCPyV status and disease specific survival. (D) Kaplan-Meier plot for perineural invasion and disease specific survival.

Supplemental Figure 3. Correlation between B7-H3/CD31 G-function co-localization index in MCPyV-negative MCCs. Plots showing the correlation B7-H3/CD31 G-function co-localization index for each primary MCPyV-negative MCC plotted against the frequency of associated malignancies (A) and lymphovascular invasion (B). G-function calculated according to a 1 pixel (1.57 �m) radius.

TT, tumor thickness; NR, not reported * Includes vulvar (n=14) and vaginal (n=7) melanomas £ Includes vulvar (n=16), vaginal (n=1) and cervical (n=1) melanomas Â¥ Includes vulvar (n=61), vaginal (n=15), urethral (n=5) and cervical (n=4) melanomas Â,¬ Includes vulvar (n=33) and vaginal (n=11) melanomas Î' Includes vulvar (n=58), vaginal (n=11), cervical (n=7) and other (n=9) melanomas

(A, B, C) We first assigned patients with PVM to a T-category according to the AJCC for PCM (7th Edition). (A) Shows the AJCC schema and the number of patients assigned to each category. (B) Kaplan Meier DSS curves for patients stratified by AJCC T-categories demonstrate robust prognostic differences for patients with PVM and pT1 and to an extent pT2 disease from those with pT3 and pT4 disease, but less robust stratification among those patients with PVMs {less than or equal to}2.00 mm; pT1 versus pT2 (isolated in C) or >2.0 mm; pT3 and pT4. (D, E, F) Because both tumor thickness and mitotic rate were independent prognostic factors for DSS and because mitotic rate showed a natural prognostic separation at 2 mitotic figures/mm2 (as shown in Figure 1D), we first asked whether a T-category according to the conventional AJCC cut-offs ({less than or equal to}1.0, 1.01-2.0, 2.01-4.0 and >4.0 mm) subsequently modified by mitotic rate (a: 2.0 mm (pT3 and pT4) had a short DSS independent of mitotic rate. More importantly, among patients with a tumor thickness {less than or equal to}2.0 mm (pT1 or pT2), only those with mitotic rate {greater than or equal to}2/mm2 had a short DSS, which was essentially superimposable with patients with pT3 and pT4 PVM in this schema. (F) Kaplan-Meier survival curve for patients with pT1 and pT2 PVMs show striking differences in survival according to mitotic rate (

M1a, Metastasis in skin, subcutaneous tissues, or distant lymph nodes; M1b, Metastasis to lung; M1c, Metastasis to all other visceral sites.

Supplemental Figure 4. Correlation between B7-H3/CD31 G-function co-localization index and vascular density. Plots showing the correlation B7-H3/CD31 G-function co-localization index plotted against vascular density for the whole cohort of primary MCC (vascular density tabulated as the average of the regions of interest in each of the 52 tumors).

Survival according to CD3 density/mm2 at the periphery (left), center (middle), and hotspot (right) in MCPyV+ MCCs (Top row) versus MCPyV- MCCs (Second row). Survival according to CD8 density/mm2 at the periphery (left), center (middle), and hotspot (right) in MCPyV+ MCCs. (Third Row) versus MCPyV- MCCs (Bottom row). Legend: Patients with cell densities above the median indicated with a dashed line and patients with cell density below the median indicated with a solid line.

Supplemental Table 1. Relationship Between Merkel Cell Polyoma Virus and Clinicopathologic Parameters. Supplemental Table 2. Univariate Logistic Regression Models for Metastasis to Any Site. Supplemental Table 3. Univariate Logistic Regression for Metastasis to Individual Lymph Node Beyond Sentinel Lymph Node. Supplemental Table 4. Univariate Logistic Regression for Metastasis to Sentinel Lymph Node. Supplemental Table 5. Univariate Logistic Regression for Metastasis to Central Nervous System. Supplemental Table 6. Spearman Correlation Between Cell Density and Age, Tumor Size, Depth of Invasion, and Mitotic Figures. Supplemental Table 7. Relationship Between Gender and Immune Infiltrate. Supplemental Table 8. Merkel Cell Polyoma Virus and Immune Infiltrate. Supplemental Table 9. Immune Infiltrate Cell Density: Descriptive Statistics. Supplemental Table 10. Relationship Between Anatomic Site and Immune Infiltrate. Supplemental Table 11. Relationship Between Lymphovascular Invasion (LVI) and Immune Infiltrate. Supplemental Table 12. Relationship Between Perineural Invasion (PNI) and Immune Infiltrate.

Context.— Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1− in MCC and CK20−/TTF1+ in PSmCC). Objective.— To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC. Design.— SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. Results.— SOX11 expression was present in all MCCs and was predominantly strong and diffuse. Only 19% of primary and 38% of metastatic MCCs exhibited diffuse PAX5 expression; none exhibited strong immunoreactivity. Strong and diffuse SOX11 expression was seen in less than 25% of primary and metastatic PSmCCs. PAX5 expression was rare in PSmCCs and was mostly weak and focal/patchy. SOX11 expression in at least 26% of tumor cells, with at least moderate intensity, favored the diagnosis of MCC over PSmCC (P < .001). Furthermore, SOX11 expression was more likely than CK20 expression to be strong or diffuse in sentinel lymph node (SLN) metastases of MCC, indicating that SOX11 is superior to CK20 for detecting tumor deposits in SLNs in MCC. Conclusions.— Our findings indicate that SOX11 not only is a powerful marker for distinguishing MCCs from PSmCCs, especially when used in conjunction with CK20 and TTF1, but also has utility for screening SLNs in MCC.

Cutaneous lymphoid hyperplasia (CLH) is a benign reactive process with T-cell or B-cell lymphocytic infiltration in the skin, which can simulate cutaneous lymphomas both clinically and histologically. Various antigenic stimuli have been implicated in the development of CLH, including tick bites. Finding histologic evidence of such triggering factors, however, is often difficult. Moreover, the presence of clonality in CLH can potentially be interpreted as a neoplastic process, posing a further diagnostic challenge to dermatopathologists, if one is not aware of such peculiar phenomena. Herein, we describe a case of CLH secondary to a tick bite, featuring both T-cell clonality and monotypic plasma cells with lambda light chain restriction; the diagnostic clue being tick parts, which became evident on assessment of deeper levels. To the best of our knowledge, this is the first reported case of a tick-associated clonal CLH with simultaneous detection of monoclonal T cells and monotypic lambda light chain restriction, mimicking primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder and Borrelia-associated primary cutaneous marginal zone B-cell lymphoma, respectively.

Context.— Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcome. BPDCN diagnostically overlaps with entities such as acute myeloid leukemia, histiocytic/dendritic cell neoplasms, and natural killer/T-cell lymphomas. Unfortunately, large, patient-centered studies that comprehensively analyze clinical, pathologic, and other diagnostic features are lacking. As such, there is an incomplete understanding of this disease. Objective.— To better characterize BPDCN, a multicenter working group consisting of hematopathologists and dermatopathologists gathered in person and remotely to review the current understanding of BPDCN, discuss specific issues regarding the diagnosis and differential diagnosis, and perform a retrospective analysis of the literature. Data Sources.— The working group curated a database of published BPDCN patient cases (BPDCN Network literature database) following careful discussion and review, 361 articles were identified, comprising a total of 1513 individually annotated patients. Conclusions.— By conducting an in-depth analysis, not only did we confirm known findings such as frequent skin involvement (84% of patients; 861 of 1028) and a male predominance among older patients (>60 years old; male to female ratio of 3.5:1; 617:177), but we also identified a number of underrecognized features, such as significant central nervous system involvement (38% of cases; 24 of 64), and a more equal male to female prevalence among patients younger than 40 years (male to female ratio of 1.25:1; 167:134). Furthermore, we were able to accurately summarize the immunophenotypic, cytogenetic, and molecular features of this disease. BPDCN is a complex disease with distinct morphologic, immunophenotypic, and molecular findings. Continual updates of the literature database generated here and further analysis can allow for prospective refinement of our understanding of this orphan disease.