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Corresponding author at: Foundation IRCCS Ca’ Granda - Maggiore Hospital Policlinico, Division of Gastroenterology and Hepatology, Via F. Sforza 35 – 20122 Milan, Italy.
A 71-year-old woman was transplanted for primary biliary cholangitis (PBC) in 2006,
with graft function that was persistently normal during follow-up, as well as normal
liver stiffness (FibroscanⓇ) and abdominal doppler ultrasound. Immunosuppression was
CNI-based (tacrolimus, blood level=4 µg/L) and everolimus (blood level 2.3 µg/L) added-on
in 2014 (diagnosis of PTLD TCD8+, CD 30-, BOM negative). In December 2019, the patient
presented with the appearance of a diffuse arthro-myalgia; pancytopenia; abnormal
alkaline phosphatase and Gamma-glutamyl-transferase (364/231 IU/L). Thus, a liver
biopsy was performed in January 2020. Histology revealed a diffuse hepatic infiltration
of high-grade neuroendocrine carcinoma (NEC) showing high proliferation-index (Ki-67 80%) (Fig. 1) [
]. A disease staging by imaging included: 1-TC-scan showing thoracic-axillary-abdominal
adenopathies; an inhomogeneous colliquated lesion (6 cm) in mediastinal region; an
inhomogeneous liver graft with multiple hypodense areas and lumpy margins; 2- A PET-TC
revealed the presence of high glucose metabolic activity of hetero-productive significance
of the mediastinal lesion; multiple lymphadenopathies; diffuse similar activity in
the liver and at the medullary level (Fig. 2); 3- EGD: microfoci of neoplastic infiltration of the gastric lamina propria; 4-
A Bone marrow aspirate/biopsy showed massive infiltration of NEC, as also was shown by fine-needle aspiration of the mediastinal lesion and axillary
lymph node, with probable pulmonary primitivity. The oncological program including
mutational characteristics of the neoplasm was started but not concluded after hospital
discharge. In fact, at the end of March 2020 the patient developed a severe respiratory
failure and died from Covid-19 infection.
Fig. 1Liver parenchyma with diffuse portal and sinusoidal neoplastic infiltration (A, H&E
100x); tumor cells show medium-large size, spindle, or ovoid nuclei, with very scant
cytoplasm (B, H&E 400x), and demonstrate diffuse immunoreactivity for neuroendocrine
markers (C, Synaptophysin 200x) and high Ki67 proliferative index (D, MIB1 400x).
Fig. 2A. CT Scan showing solid lesion in the upper right paramediastinal region of 6 cm,
inhomogeneous, adhering to the mediastinal pleura with hetero-productive appearance.
B. PET showing intense and inhomogeneous accumulation of tracer in the liver site of
known hetero-productive disease, with more intense and confluent areas, particularly
in the II, IV and V segment (SUV max 9.8). C. CT scan with enlarged liver, lumpy outlines, inhomogeneous parenchyma, due to the
presence of hypodense areas with blurred edges in the IV-V segment.
