Keywords
aleukemic leukemia cutis -
18F-FDG PET/CT - penile and scrotal involvement - cutaneous manifestation - cancer imaging
Introduction
Aleukemic leukemia cutis (ALC) presents as discrete atypical leukemic cells infiltrate
the skin in the absence of circulating blasts or bone marrow findings consistent with
leukemia. This entity is associated with a poor prognosis and usually precedes clinically
detectable leukemia by weeks to months.[1] LC could present as the first sign of a new diagnosis of leukemia. The role of 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) in the diagnosis,
staging, tumor biology evaluation, and therapy response assessment in several hematological
malignancies is well documented, and the evaluation of disease burden is an important
decision-making marker that impacts the patient management and disease prognosis significantly.
Case Study
A 49-year-old male presented with multiple subcutaneous nodules and joint pains. The
attending clinicians came to an initial tentative diagnosis of gout, with suspicion
of rheumatoid arthritis as there was associated right knee and ankle joint swelling.
The blood counts and chemistry including liver function tests were found to be within
normal limits. Elevated lactate dehydrogenase and uric acid levels were noted. On
further workup, the CT scan of the chest, abdomen, and pelvis revealed multiple nodules
in abdomen, chest wall, upper thigh, and right testis with associated bilateral pleural
effusion. Subcutaneous nodule biopsy revealed LC with dense mixed dermal intracellular
infiltration that involved vascular capillaries and adnexal structures. Bone marrow
aspiration revealed normocellular myeloid preponderant bone marrow with mild increase
in eosinophils, M/E ratio 635:1; the erythroid series revealed reduced cellularity
(12%); megakaryocytic series revealed adequate cellularity; myeloid series (%) revealed
promyelocytes (0), myelocytes (07), metamyelocytes (02), polymorphs (69), eosinophils
(07), basophils (0), monocytes (0), promonocytes (0); and lymphoid series (%) revealed
adequate mature lymphocytes. The bone marrow biopsy report revealed hypocellular marrow,
predominantly cartilage scanty marrow spaces showing trilineage hematopoiesis. The
myeloid series was normal with mild increase in eosinophils, adequate megakaryocytes,
and erythroid series was mildly reduced with normal maturation. A whole-body 18F-FDG PET/CT ([Figs. 1], [2]) undertaken 60 minutes after intravenous injection of 6.7 mCi of 18F-FDG, using a whole-body full-ring dedicated three-dimensional PET-CT scanner (Gemini
TF; 250 mAs, 120 kVp, noncontrast CT scan), revealed multiple hypermetabolic soft
tissue attenuation nodules in region of right shoulder (maximum standardized uptake
value [SUVmax]: 17.5), right lateral chest wall, right forearm anterior aspect, left arm and forearm,
anterior abdominal wall at the level of pelvic inlet, bilateral root of penis, largest
in left inguinal region measuring 3.3 × 2.3 cm (SUVmax: 18.2), left gluteal, left popliteal fossa, bilateral ankle involvement. Hypermetabolic
ill-defined soft tissue attenuation involving the entire length of penile shaft with
central necrotic area (SUVmax: 19.2) was associated with hypermetabolic diffuse skin thickening ([Fig. 3]). Linear and avid uptake was noted in lateral compartment muscles of left leg (SUVmax: 18) ([Fig. 2]), with hypermetabolic left level V, right axillary, right popliteal, bilateral inguinal
nodes (number of nodes right > left with SUVmax: 17.5), and diffuse hypermetabolic marrow in humerii and femora with significant
epiphyseal and metaphyseal marrow involvement of distal right femur (SUVmax: 22.5) ([Fig. 1]). Ametabolic right pleural effusion, pericardial effusion, ascites, and diffuse
subcutaneous edema were noted. Liver and spleen revealed no definitive focal FDG uptake
and no lung nodule was noted in the whole-body survey. Despite prompt investigations
and medical management, the patient succumbed in 15 days post-FDG PET/CT.
Fig. 1 (A) Maximum intensity projection (MIP) positron emission tomography (PET) image; (B–D) computed tomography (CT), PET, and fused PET/CT axial images showing metabolically
active ill-defined soft tissue attenuation involving the entire length of penile shaft
with central necrotic area (maximum standardized uptake value [SUVmax]: 19.2); (E–G) CT, positron emission tomography (PET), and fused PET/CT coronal images showing
metabolically active nodules in right forearm anterior aspect, right inguinal nodes,
penile bulb; (H–J) CT, PET, and fused PET/CT sagittal images showing metabolically active soft tissue
attenuation nodules in root of penis (SUVmax: 18.2), penile bulb, diffuse skin thickening of scrotum. Hypermetabolic diffuse involvement
of bone marrow of both femora, with associated intense uptake in marrow of right femur
in distal epiphysis (SUVmax: 22.5) (MIP image A).
Fig. 2 (A–C) Computed tomography (CT), positron emission tomography (PET), and fused PET/CT axial
images showing metabolically active subcutaneous regions in both ankles; (D–F) CT, PET, and fused PET/CT coronal images showing linear hypermetabolism uptake noted
in left leg-lateral compartment muscles (arrow), maximum standardized uptake value (SUVmax): 18; (G–I) CT, PET, and fused PET/CT sagittal images showing metabolically active left inguinal
subcutaneous nodule—largest right measuring 3.3 × 2.3 cm, SUVmax: 17.5.
Fig. 3 Anon-contrast computed tomography (CT) axial image showing ill-defined soft tissue
attenuation in penile shaft with central necrotic area; (B) fused positron emission tomography/computed tomography (PET/CT) axial image showing
metabolic activity involving the entire length of penis (maximum standardized uptake
value [SUVmax]: 19.2); (C) fused PET/CT coronal images showing metabolically active right inguinal nodes and
penile bulb; (D) fused PET/CT sagittal images showing metabolically active soft tissue attenuation
nodules in root of penis-largest in left inguinal region measuring 3.3 × 2.3 cm (SUVmax: 18.2), penile bulb, and diffuse skin thickening of scrotum.
Discussion
The present case thus portrays a patient of ALC, with extensive subcutaneous leukemic
deposits, atypical penile, and scrotal involvement documented on 18F-FDG PET/CT and a rapidly fatal disease course. LC is an important yet under-studied
extramedullary manifestation of leukemia,[2] characterized by clinically visible skin lesions (nodules or erythematous papules)
caused by skin infiltration of neoplastic leukocytes.[3] Most of the patients are male and the most common associated malignancy has been
acute myeloid leukemia.[3] The present case was also a male, a rapidly progressive course developing skin nodules
more in torso including penile and scrotal involvement, and succumbed in less than
a month postdiagnosis indicating the importance of high suspicion and diagnosis for
initiating the appropriate line of management early in the disease course.
More commonly, ALC is noted in the setting of a previously diagnosed hematological
malignancy, but rarely it may be the first sign of leukemia.[4]
[5] In our patient, there was no history of prior hematologic disorder and LC preceded
blood or bone marrow manifestations of leukemia. Zheng et al in their report observed
that FDG-PET/CT revealed widespread cutaneous and subcutaneous hypermetabolic lesions
in many parts of the body, and heterogeneously increased uptakes in the bone marrow.
Later, the bone marrow biopsy and second skin biopsy were performed. Pathological
examination from both specimens demonstrated acute monocytic leukemia.[6] In our patient, skin biopsy already had proven LC. Bone marrow biopsy had revealed
hypocellularity, while further FDG-PET/CT revealed multiple subcutaneous hypermetabolic
nodules, atypical penile shaft, and scrotal with leg muscle involvement.
LC lesions are seldom seen on the genital organs. One case of a well-differentiated
myeloid sarcoma in the penile foreskin in an apparently healthy 29-year-old male presenting
with phimosis and simultaneous priapism where a cutaneous myeloid sarcoma was reported
in the penile foreskin first time.[7] LC typically presents on the face and neck as well as exposed areas. Ng at al published
a 78-year-old gentleman with known chronic lymphocytic leukemia (CLL) and asymptomatic
raised lesion in his inner prepuce. The lesion immunohistology was consistent with
cutaneous manifestation of CLL, highlighting the importance of taking LC into consideration
in patients with known CLL with unusual features.[8] Plaza et al in their paper on cutaneous manifestations reported that they are an
uncommon presentation of subclinical B cell CLL, highlighting the importance of maintaining
a high index of suspicion for a lymphoproliferative process in cases with unusual
or atypical clinicopathologic features.[9]
The role of FDG PET/CT in cancer imaging is reported in literature in evaluating primary
and staging of penile cancer, penile metastasis from malignancies like renal cell
carcinoma, and malignancies of urogenital system (urothelial bladder, prostate) or
the rectosigmoid and colon. LC is often associated with additional locations of extramedullary
involvement and can forecast a poor prognosis.[5]
[10] Given its diverse and nonspecific clinical presentation, LC diagnosis relies exclusively
on immunohistochemistry,[11] which identifies myeloid cells of LC, with CD68 and CD43, as first-line stains.[1] FDG-PET/CT can be an important whole-body modality evaluating the disease extent,
precisely informing sites of involvement and guiding treatment, with its potential
role in posttreatment response assessment.
Conclusion
In summary, in our patient, LC was the first manifestation of leukemia and predated
hematological manifestation. In the described patient, FDG-PET/CT revealed extensive
uptake in the subcutaneous leukemic deposits, atypical penile and scrotal leukemic
involvement, and leg muscles, highlighting the role of metabolic imaging in this condition.
