case_images: PMC7358364_01
case_images: (A) Sample of lymph node metastasis performed before SSA therapy showing an epithelioid feature of cells with "salt and pepper" nuclei (EE40x). Immunohistochemistry showed (a) positivity for Ki67 in 25% of cells (20x); (b) positivity for CK20 with nuclear dot (20x); (c) positivity for chromogranin A with nuclear dot (20x); (d) nuclear positivity for poliomavirus Merkel cells carcinoma associated/CMV (40x); (e) diffuse and strong membranous positivity for somatostatin receptor 2A (SSTR2A) (20x); (f) negativity for p63 (10x); and (g) for PDL-1 (20x). (B) Sample of lymph node metastasis performed after disease progression to SSA therapy showing cells having smaller size than those of pre-treatment and a round shape with dark nuclei (40x). Immunohistochemistry showed (a) Ki67 positivity in 85% of cells (20x); (b) reduction of positivity for chromogranin (20x); (c) diffuse nuclear positivity for p63 (40x); (d) strong positivity for PDL-1 in 35% of neoplastic cells (10x).
case_images: fonc-10-01073-g0001.jpg
case_images: PMC7358364_01_fonc-10-01073-g0001.jpg
case_images: F1
case_images: At the diagnosis, immunohistochemistry reported a Ki67 of 25% and a positivity for synaptophysin, chromogranin A, CK20, nuclear polyomavirus marker, and SSTR2A, whereas SSTR5A, PD-L1, and p63 (a transcription factor often associated with worse prognosis) were negative (Figure 1A). Due to the high expression of SRs at octreoscan with 99mTc-EDDA/HYNIC-TOC (Figure 2) and at immunohistochemistry (Figure 1A), the patient started the SSA octreotide at the dose of 30 mg intramuscularly every 28 days obtaining a progressive decrease of serum markers and a partial regression of disease lasting over 2 years. Immunohistochemistry also showed a Ki67 of 85% compared to 25% of the first biopsy, whereas p63 and PD-L1 became strongly positive (Figure 1B).
case_images: Octreoscan showing high uptake of 99mTc-EDDA/HYNIC-TOC in the right axillary and thoracic wall, in the left sub-mandibular and latero-cervical region, and at right superior pulmonary lobe in the sub-pleurical region. On the right is shown the membranous diffuse expression of SSTR2A on immunohistochemistry.
case_images: fonc-10-01073-g0002.jpg
case_images: PMC7358364_01_fonc-10-01073-g0002.jpg
case_images: F2
case_images: Due to the high expression of SRs at octreoscan with 99mTc-EDDA/HYNIC-TOC (Figure 2) and at immunohistochemistry (Figure 1A), the patient started the SSA octreotide at the dose of 30 mg intramuscularly every 28 days obtaining a progressive decrease of serum markers and a partial regression of disease lasting over 2 years.
case_images: CT scan performed before therapy with the association octreotide plus avelumab (A) and after 10 months of therapy (B).
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case_images: PMC7358364_01_fonc-10-01073-g0003.jpg
case_images: F3
case_images: After four administrations of avelumab, an impressive response was observed until achieving a complete remission (Figures 3A,B).
case_images: Behavior of chromogranin A (CgA), Neuron-Specific Enolase (NSE), and peripheral lymphocytes count during octreotide and then during the association of octreotide plus avelumab.
case_images: fonc-10-01073-g0004.jpg
case_images: PMC7358364_01_fonc-10-01073-g0004.jpg
case_images: F4
case_images: At this time, circulating CgA remained under normal value whereas NSE increased rapidly (Figure 4). Also circulating NSE level progressively decreased until normal value (Figure 4). Then, lymphocytes progressively decreased until pre-treatment value (Figure 4).