The Skin as an Early Expression of Malignancies in the Neonatal Age: A Review of the Literature and a Case Series

Table 2

Diagnostic tests in malignancies involving the skin, with differential diagnosis ( in addition to the different causes of blueberry muffin baby listed in Table 1; WBC: white blood cell; Hb: Haemoglobin; PLTs: platelets).

Neoplasia	Diagnostic tests	Differential diagnosis
Leukemia	(i) Blood cell count (WBC > 50000; low Hb and PLTs); (ii) Liver function tests; (iii) Coagulation studies; (iv) Blood film; (v) Bone marrow aspirate with morphology, immunophenotype (FAB L1, L2, M4, M5, and M7), and karyotypes [t(4;11)(q21;q23); t(11;19)(q23;p13); t(9;11)(p21;q23); t(1;22)(p13;q13)] of blasts; (vi) Skin biopsy	(i) Listeriosis; (ii) Sepsis; (iii) Intrauterine Parvovirus infection; (iv) Congenital HIV; (v) Diamond Blackfan anemia; (vi) Extramedullary hematopoiesis; (vii) Intrauterine or birth-related hypoxia; (viii) Neonatal lupus erythematosus
TMD	(i) Blood cell count (WBC 100000–50000 or normal; normal or decreased Hb; and decreased PLTs); (ii) Liver function tests (increased bilirubin and/or transaminases); (iii) Coagulation studies (abnormal coagulation); (iv) Renal function tests; (v) Abdominal ultrasound; (vi) Echocardiography; (vii) Chest X-ray; (viii) Blood film; (ix) Bone marrow aspirate with morphology, immunophenotype (FAB M7), and karyotypes (GATA 1) of blasts	(i) Nonspecific changes associated with intrauterine growth restriction and trisomies: neutropenia, thrombocytopenia, erythroblastosis, and polycythaemia; (ii) Subtle myelodysplastic features: abnormal myeloid cell granulation, giant platelets
LCH	(i) Blood cell count (normal or decreased Hb, RBC, and/or PLTs); (ii) Liver function tests; (iii) Coagulation studies; (iv) Chest X-ray; (v) Abdominal ultrasound; (vi) Skin biopsy	(i) Hemophagocytic lymphohistiocytosis; (ii) Familial erythrophagocytic lymphohistiocytosis; (iii) Infection-associated hemophagocytic syndrome; (iv) Hemangioendotheliomas; (v) Extramedullary hematopoiesis; (vi) Lymphatic malformations; (vii) Infantile myofibromatosis; (viii) Histiocytomas; (ix) Fibrosarcoma; (x) Peripheral Primitive Neuroectodermal Tumor
NB	(i) Blood cell count (possible anemia and cytopenias); (ii) Lactate dehydrogenase levels; (iii) Ferritin; (iv) Liver and renal function tests; (v) Urine catecholamines (increased homovanillic and vanillylmandelic acid); (vi) Abdominal and cerebral ultrasound; (vii) Chest X-ray; (viii) If necessary, brain, neck, and chest MRI; (ix) Skin biopsy with karyotypes (MYCN amplification); (x) Bone marrow aspirate	(i) Benign cutaneous epithelioid Schwannoma; (ii) Ganglioneuroma; (iii) Ganglioneuroblastoma
RT	(i) Urinalysis and renal function tests; (ii) Abdominal ultrasound; (iii) Chest X-ray; (iv) Brain ultrasound; (v) If necessary, brain MRI; (vi) Skin biopsy with karyotypes (SWI/SNF at 22q11.2)	(i) Wilms’ tumor; (ii) Medulloblastoma; (iii) Sarcomas; (iv) Hemangioma
RMS	(i) Blood cell count (normal or decreased PLTs, anemia); (ii) Liver function tests	(i) Wilms’ tumor; (ii) Sarcomas