Introduction
Blastic plasmacytoid dendritic cell neoplasms (BPDN) are exceeding rare T-cell neoplasms
that carry a dismal prognosis. Today, the exact etiology of the disease is unclear,
and to our knowledge, no cases of BPDN have been reported at the site of vaccination
injection. Additionally, all currently described cases described have dismal prognosis,
and, to our knowledge, there are no reports of such lesions responding to topical
steroid treatment. Herein, we present an unusual case of BPDN occurring at an influenza
vaccination site that subsequently resolved after high-potency topical steroid treatment.
Case report
A 71-year-old white man with no significant medical history presented with a 5.0-cm
nontender, erythematous, and scaling plaque with an indurated border on the left upper
arm. The lesion appeared at the site of an influenza vaccination that he received
7 days prior. The patient denied systemic symptoms and any such reaction with previous
vaccinations. The initial clinical suspicion was that of an injection site hypersensitivity
reaction. A punch biopsy was performed, and a topical high-potency steroid, diflorasone
diacetate 0.05%, was prescribed.
The biopsy found an atypical dense lymphoid infiltrate in the papillary and reticular
dermis. A grenz zone was present. The infiltrate shows prominent perivascular distribution
(Fig 1). The individual lymphocytes had hyperchromatic nuclei with irregular nuclear
contour and nucleoli (Fig 2). Crush artefact was present at the periphery of the biopsy
section.
Immunohistochemical profiling found the lesion to be diffusely CD4+ and CD56+ (Fig
3). Most of the lesional cells were also CD123+ and TdT+ (Fig 3). Repeat CD123 staining
found more intense and diffuse positivity. Admixed were rare CD79+ B cells. Tests
for myeloperoxidase, CD34, MUM1, PAX5, CD3, CD10, CD21, kappa, and lambda were negative.
Epstein Barr virus in situ hybridization results were also negative. In addition to
these markers, an outside hospital found that our lesion was TCL1+ and CD117− and
muramidase negative. After histologic and immunoprofiling of CD4+, CD56+, TCL1, and
CD123+, a diagnosis of BPDN was rendered. Differential diagnosis included extramedullary
myeloid sarcoma and an acute leukemia with ambiguous lineage. Absence of myeloperoxidase
excluded myeloid sarcoma, and absence of CD34, myeloperoxidase, CD117, and muramidase
ruled out acute leukemia. This diagnosis was confirmed by a senior hematopathologist
and at major cancer center. At the 2-week follow up, the patient reported that the
entire lesion had resolved with topical steroid treatment. Despite the lack of clinical
evidence of disease, radiation therapy was delivered at the site. At the time of this
report, bone marrow and blood involvement were not found and leukemia was excluded,
but watchful follow-up is necessary.
Discussion
BPDN is a rare and aggressive hematologic disease, the etiology, incidence, clinical
presentation, and treatment strategies of which are still being elucidated. Derived
from precursors of plasmacytoid dendritic cells, BPDN is categorized under “acute
myeloid leukemia and related precursor neoplasms” by the 2008 World Health Organization
classification.1, 2 Most patients are elderly men, with a male to female ratio of
2.2:1 to 3:1 and a median age of approximately 67 years.2, 3 Pediatric cases have
also been reported, and the clinical progression appears to be less aggressive with
a more favorable prognosis.
4
No racial or ethnic preferences have been found. The incidence of BPDN among cutaneous
lymphomas is 1.4%.
5
Patients most commonly present with cutaneous lesions, ranging from isolated or few
purplish nodules, bruiselike macules, and disseminated macules and papules to lymphadenopathy.
2
Pulmonary and central nervous system symptoms may also occur. Cytopenia, splenomegaly,
hepatomegaly, and other symptoms of leukemic dissemination signify disease progression.
Fulminant leukemia indicates terminal illness. Regardless of the initial clinical
presentation, prognosis is poor. Among patients presenting with primarily cutaneous
symptoms, with or without lymph node, central nervous system, or bone marrow involvement,
median overall survival was 12 months.
2
Among patients presenting with leukemic involvement, with or without cutaneous symptoms,
median overall survival was 8.7 months.
3
Patients receiving treatment in the early cutaneous phase of disease, with isolated
or few lesions, may have more favorable outcome. Poor prognostic indicators include
advanced age and clinical staging.2, 3 Children with BPDN have improved median overall
survival when given the same treatment as adults.
4
Given the low incidence of the disease, no standard of care has been established for
BPDN, and determinations of treatment efficacy rely on retrospective case or registry
studies. Induction therapy includes focal radiotherapy, chemotherapy, and glucocorticosteroids
to address cutaneous lesions. Late-stage disease treatments include cyclophosphamide,
hydroxydaunomycin, vincristine, prednisone and hyperfractionated cyclophosphamide,
vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine,
but relapse occurs within months of remission on average.
6
Patients that undergo hematopoietic stem cell transplantation (HSCT), often used to
maximize consolidation of response or after relapse, show the greatest promise for
long-term response, with better survival curves and overall survival rates than patients
that only had conventional therapies. These determinations are primarily anecdotal
from case studies, with small sample sizes and populations skewed toward younger males,
so robust statistical evaluations are lacking.7, 8, 9 In one study of 47 patients
with BPDN, overall survival in HSCT patients was significantly higher than that in
non-HSCT patients (31.3 months vs 12.8 months).
9
Misdiagnosis is common, leading to delayed treatment, as BPDN can be morphologically
and clinically indistinguishable from leukemia cutis and acute myeloid leukemia. Immunophenotypic
analysis, morphology, and clinical details are used for definitive diagnosis. As of
now, there is no consistent immunophenotypic algorithm for pathologic diagnosis of
BPDN. The most characteristic markers for BPDN are CD4, CD56, CD123, CD303, and TCL1.
In one retrospective study, diagnosis by immunophenotype was considered definite when
patients coexpressed at least 4 of these main markers.
10
In our case, positivity in 4 of these 5 main markers, along with exclusion of myloid
sarcoma and acute leukemia of ambiguous origin from negative markers as described
above, allowed for diagnostic completeness.
The etiology and pathogenesis of BPDN remains largely unknown. Studies into normal
physiologic counterparts to malignant BPDN cells yielded plasmacytoid dendritic cells
and plasmacytoid dendritic–like cells as candidates.11, 12 A review of molecular data
found that abnormalities in chromosomes 5, 9, 12, 13, and 15 are nonuniformly involved
in pathogenesis, suggesting a diversity of genetic mutations that can dysregulate
oncogenic pathways in BPDN.
6
Epstein-Barr virus is not associated with BPDN.
1
A review of literature found that BPDN can manifest with a variety of cutaneous phenotypes.
Julia and et al
2
observed a pattern of few lesions in early disease, progressing to cutaneous dissemination
in late disease. The lesions ranged in type and color, described as nodes, patches,
plaques, and tumors, of brown or violaceous appearance.
2
Given the variety of its cutaneous manifestations and low incidence, BPDN can be mistaken
for eczema or lupus erythematosus, leading to delay in appropriate treatment.13, 14
In the English-language literature, there are no reports, to our knowledge, of BPDN
occurring at the vaccination site. In addition, BPDN also carries a poor prognosis,
and the regression of our patient's lesion with topical high potency steroid makes
our case novel and intriguing. The diagnosis of this lesion is dependent on histologic
and immunologic evaluation. To date, there is no specific molecular test to confirm
a diagnosis of BPDN. Therefore, based on the current standards, a diagnosis of BPDN
was made on our biopsy. However, the atypical presentation and behavior of our case
raises the question if our lesion was indeed a distinct presentation of BPDN that
carries a good prognosis or was a BPDN-like reaction to the vaccination. At the time
of this report, the benign clinical course of this case is highly uncharacteristic
of BPDN. Regardless, given the possibility of true BPDN and the prognosis it carries,
any such lesion with characteristic histology and immunophenotype should be met with
extreme suspicion, and treatment measures appropriate to BPDN should be considered.