Abstract
Blastic plasmacytoid dendritic cell neoplasm is an aggressive and rare
hematologic malignancy, exceptionally presented in children. This case
reports an 11-year-old Peruvian boy, with a 2-year history of a
purple-violate tumor in a leg, lymph node involvement, and
histopathological study with immunohistochemistry: CD4+, CD56+, Tdt+,
CD45+, TCL1+. An institutional treatment protocol for high-risk ALL was
given. There was a diagnosis delay in a pediatric patient with a rare
but very visible neoplasm in a low-middle income country. Despite this,
the clinical course was of an indolent evolution. The institutional
protocol was efficient to achieve complete oncological disease response.
Introduction
Blastic Plasmacytoid Dendritic Cell
Neoplasm (BPDCN) is a rare hematological neoplasm, which has its own
category in the group of leukemias 1. It usually
presents in elderly people, and its clinical manifestations include
nodular blue-violet skin lesions, bone marrow infiltration and, less
frequently, extramedullary involvement 2. These
clinical characteristics do not differ significantly between age groups;
however, better survival has been found in pediatric cases2,3. Despite some associations with other hematologic
neoplasms, its etiology is still unknown 4. Diagnosis
is based on immunohistochemistry, it requires positive CD4 and CD56, and
at least two positive dendritic cell markers5.
Current literature, based on case
reports, supports the use of acute lymphoblastic leukemia (ALL)
treatment regimen as the most beneficial option 6.
While new therapies that target CD123 and SL-401 (tagraxofusp)7 are currently being studied for a more specific
treatment in adults, they still have to be tested in a pediatric
population8.
The objective of the present pediatric clinical case is
to document both a diagnosis of this indolent and rare disease, whose
natural history in Latin American patients is usually ignored in
published reviews; and report complete remission after appliance of an
institutional treatment regimen for high-risk acute lymphoblastic
leukemia
(HR-ALL).
Case report
The case of an 11-year-old boy, from Yungay (Ancash,
Peru) is reported. He was referred from Ancash Hospital to the National
Institute of Neoplastic Diseases (INEN) in Lima, with the diagnosis of
’Round Cell
Neoplasia’.
This child presented with a 2-year clinical history,
characterized by the presence of a growing tumour in the anterior inner
middle third of the right leg, of approximately 5 centimeters by time of
medical consultation, blue-violet colouring, increased consistency,
poorly defined edges and little pain on palpation. No epidemiological,
personal, family or medical history of importance was
reported.
At physical exam he presented a 7 cm long surgical scar
with ulcerated area and granulation tissue without signs of infection,
presence of right inguinal adenopathies of 3x3 cm, mobile, painless,
without phlogosis was
found.
The child had a prior biopsy in Ancash, but it was
insufficient tissue and INEN’s oncopediatric team performed a new
biopsy. Hematoxylin and eosin staining and immunohistochemical markers
were studied. It showed CD4+ and CD56+; staining for more specific
markers resulted in a local TdT+, CD45+, TCL1+ and CD34 -. In addition,
a KI-67 score of 60%. (Fig.
1)
Significant lymphadenopathies in the right external iliac chain and
right inguinal region were found through Multi-slice spiral computed
tomography. Theses typical secondary lesions were considered as inguinal
metastasis.
Laboratory values of hemoglobin, leukocytes, segmented, platelets, and
erythrocyte sedimentation rate values were normal. Morphology, flow
cytometry and bone marrow biopsy were negative to infiltration of
neoplasm cells.
Final diagnosis was BPDCN. After the medical team discussion, an
institutional HR-ALL treatment protocol, based on the pediatric one from
the International BFM Study Group (BFM-95), was indicated (Table 1). The
high-risk classification was mainly indicated because of the patient’s
age and the biological characteristics of this rare disease.
During treatment, two emergency admissions were required due to febrile
neutropenia, both resolved without complications. By the date of submit
of this report, the patient was in good general condition. He completed
maintenance chemotherapy block in May 2020, and stays in controls
without treatment related complications.
Discussion
By the year 2017, a review found only 74 pediatric cases of BPDCN
worldwide 2. However, it did not included data in
Spanish or from Latin America, so these patients’ clinical evolution has
not been considered. Also, we
reported a delay in diagnosis due to lack of resources at a hospital
outside the country’s capital (as seen in many low-middle income
countries), and the indolent course of the neoplasm.
Various studies identify skin involvement as the initial manifestation
(76% of adults and 79% of children) and also the most frequent2. These lesions are often asymptomatic and purplish
or erythematous in appearance; however, they can also be pseudo-purple,
plaque, nodular, equimotic, scaly or ulcerated 7. The
most compromised regions are usually the face, scapular region and to a
lesser extent the trunk and extremities 3. In this
pediatric case of BPDCN, skin involvement was exclusively appendicular,
it compromised soft tissue (solid tumor) and had a loco-regional
presentation in the lower right limb (inner side of the right leg with a
purplish tone).
Bone marrow compromise and leukemic expression can appear even without
skin lesions in 60-90% of cases 2,3. In this child,
even after two years of evolution before the diagnosis, there was no
bone marrow infiltration. Extramedullary manifestations can include
involvement of the liver, lymph nodes (40%-50%), sinuses, orbits and
central nervous system, rarely splenomegaly (20%) and fulminant
leukemia (5-25%) 2,3, in this case only lymph node
involvement was registered (right inguinal).
Diagnosis confirmation was made through immunohistochemistry and by
excluding more frequent neoplasms. Thus, the positivity for CD4, but
negativity of CD3, served to rule out a T cell neoplasm. In the same
way, a positivity for CD56, but negativity for CD3, removed the
possibility of T-NK lymphocyte involvement; and negativity for CD34
excluded the presence of myeloid cells 5.
Immunohistochemistry showed CD4+, CD56 +, in addition to 2 positive
dendritic cell markers (CD123 and TCL1) which allowed confirmation of
the diagnosis 9.Other dendritic cell markers not
tested in this case are CD68, CD123 and BDCA-2/CD30310.
It has also been documented that thrombocytopenia, anemia and, to a
lesser extent, neutropenia can appear in these patients’ blood counts3. On the contrary, this patients’ initial values were
within normal parameters.
Overall patient survival of 37 months was consistent with studies where
the mean survival of patients under 40 years was 38 months2. And with other studies where the overall survival
in children at 3 years was 57.4+/- 10.2 months 11.
Treatment of BPDCN in pediatric patients is still controversial. Even if
some intents have been made to create a scheme of treatment12, a gold standard is still far away. Most cases
report good response with the same scheme used for ALL, recording
remission rates of 93%, compared to 77% of the regimen for chronic
myeloid leukemia and 80% of the scheme for lymphoma2,5,12. The most favorable results are usually seen in
patients without skin involvement 3. Protocol for ALL
includes prophylaxis of the nervous system with intrathecal
chemotherapy, since it is considered one of the main causes of morbidity
and mortality in patients with this disease 7. Bone
marrow transplantation is usually reserved for cases with one or
multiple relapses; in elderly patients is also used as a consolidation
therapy after chemotherapy 8,11,13. However, in
pediatric patients it does not improve survival 2. In
this patient, institutional HR- ALL was given with good results,
adding to the literature its efficacy in a different sociodemographic
setting.14
BPDCN is a diagnostic and therapeutic challenge. Even
with a very visible lesion, diagnostic delayed was presented in a
peruvian setting. The decision of the oncopediatric team was based on
literature and similar unpublished cases from the institution. Emphasis
should be placed on timely diagnostic through the use of
immunohistochemical markers. The treatment of BPDCN with an
institutional high-risk ALL regimen has reached very good results in
this pediatric case, achieving 37-month overall and progression-free
survival.
Ethics Statement
Informed consent was signed by the patient’s
proxy.
Conflict of Interest
Statement
The authors declare no conflict of
interest.
The authors would like to thank Melvi Guerrero Quiroga MC for her
assistance with Histopathology´s images.