Post-transplant malignancy: Focusing on virus-associated etiologies, pathogenesis, evidence-based management algorithms, present status of adoptive immunotherapy and future directions

Table 8 Post-transplant virus associated malignancy and their diagnosis

Post-transplant viral associated malignancy	Diagnosis
CIN and cervical cancer and (HPV- associated)	Abnormal cervical Pap test/cytology on screening: Colposcopy biopsy of any suspicious lesion[28,161]
AIN and anal cancer (HPV-associated)	Abnormal anal Pap test/cytology on screening: High-resolution anoscopy ± biopsy of any suspicious lesion[28,161]
EBV associated PTLD	Identify “B” symptoms (fever, night sweats and weight-loss)
	Excision biopsy/core biopsy (in allograft PTLD as excision in not practical) is gold standard for diagnosis[46]
	Stage PTLD with CT imaging of the chest, abdomen, and pelvis, as well as MRI brain imaging before initiating treatment as in immunocompetent host[166]
	PET-CT may help in diagnosing occult PTLD, accurate staging in occult cases and sometime evaluating treatment response[167-169]
PT-KS	Examine for cutaneous or mucosal lesions, visceral involvement and haematological manifestations
	Diagnostic gold standard: HHV8 confirmation in biopsy of KS lesions[170]
	HPE characteristic of PT-KS: Spindle-shaped cells and immunostaining confirmation with latency-associated nuclear antigen and CD34 positive staining[171,172]
	Quantitative PCR load of HHV8: Role in supporting diagnosis and monitoring treatment response
	Confirmation of diagnosis by HPE and HHV8 DNAemia
	Depending on site involved, disease staging by imaging and invasive procedures (e.g., bronchoscopy, esophago-gastroduodenoscopy, colonoscopy)[173]
MCD	Watch for lymph node enlargement, systemic inflammatory symptoms
	Gold standard for diagnosis: Lymphnode biopsy confirmation of HHV8[170]
	HPE: HHV8+ plasmablasts in follicular mantle zone and vascular hyperplasia
	Quantitative PCR load of HHV8: Role in supporting diagnosis and monitoring treatment response
	Confirmation of diagnosis by HPE and HHV8 DNAemia
PEL	Watch for effusion (pleural, peritoneal, pericardial)
	Gold standard: Confirmation of HHV8 in pleural/ascitic fluid[170]
	HPE characteristic: HHV8+ plasmablasts displaying immunoblastic and anaplastic characteristics
	Quantitative PCR load of HHV8: Role in supporting diagnosis and monitoring treatment response
	Confirmation of diagnosis by HPE and HHV8 DNAemia

CIN: Cervical intraepithelial neoplasia; HPV: Human papilloma virus; AIN: Anal intraepithelial neoplasia; MCD: Multicentric Castleman disease; PTLD: Post-transplant lymphoproliferative disorders; CT: Computed tomography; MRI: Magnetic resonance imaging; PET-CT: Positron emission tomography-computerized tomography; PCR: Polymerase chain reaction; PEL: Primary effusion lymphoma; PT-KS: Post-transplant Kaposi’s sarcoma; HHV8: Human herpes virus 8; HPE: Histopathology examination; EBV: Epstein–Barr virus.