PMC7713564_01
Clinical timeline and cross-sectional imaging. (A) Summary of the clinical course and systemic therapy. (B) Positron emission tomography (PET)/computed tomography (CT) showing the right pelvic mass before treatment in December 2018. Dark orange/white color indicates metabolic activity. (C) CT with oral and intravenous contrast showing the right pelvic mass after treatment with carboplatin and gemcitabine (Gem-carbo) chemotherapy. Dashed red circle indicates the metabolically active lesion in the previous PET scan. (D) Noncontrast chest CT before docetaxel chemotherapy in September 2019. (E) Noncontrast chest CT after three cycles of docetaxel chemotherapy. Red arrows in (D) and (E) indicate a lesion responsive to docetaxel. PSA, prostate-specific antigen.
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His prostate-specific antigen (PSA) was 30.8 ng/mL at the time of treatment initiation and responded rapidly to bicalutamide, reaching a nadir of 1.1 ng/mL in September 2018 (Fig 1A). By December 2018, the right pelvic mass had increased in size to 4.4 cm and in metabolic activity to SUV max 19.8 (Fig 1B). The patient experienced some improvement in pain, but the size of the right pelvic mass was largely unchanged (Fig 1C). At this point, the patient's lung nodules, which were previously indeterminate, had enlarged greatly (Fig 1D). CT completed after three cycles showed an interval decrease in the size of multiple bilateral lung nodules, and a decrease in size of his right pelvic mass, compatible with a therapeutic response (Fig 1E).
Histology and immunohistochemistry (IHC). (A) Hematoxylin and eosin (H&E) histology of pelvic mass biopsy showing squamous cell carcinoma. (B) H&E histology of the excisional biopsy of an abdominal (Abd) wall nodule, also showing squamous cell carcinoma. (C) H&E histology of the patient's (untreated) prostate tumor at initial diagnosis showing prostate adenocarcinoma. (D) IHC for ERG of the primary prostate tumor showing strong labeling. (E) H&E histology of the Abd wall nodule biopsy specimen used for molecular analysis. (F) IHC for ERG of the Abd wall nodule showing much weaker labeling.
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Because the appearance of the right pelvic mass was judged to be atypical for either prostate cancer or melanoma, it was biopsied by pelvic laparoscopy in November 2018 and was found on surgical pathology assessment to be consistent with a high-grade carcinoma with squamous features (Fig 2A). This nodule, together with smaller adjacent nodules, was removed by excisional biopsy in July 2019, where surgical pathology assessment demonstrated tumor features consistent with metastatic squamous cell carcinoma (Fig 2B). To further confirm the findings, we subsequently performed IHC analysis, which showed positive ERG expression on the patient's initial prostate transurethral resection, which was strongly positive for ERG protein (Figs 2C and 2D). We further performed ERG IHC assessment on the patient's recent abdominal biopsy, which demonstrated focal and weak-to-moderate ERG protein expression, supporting a clonal phenotypic origin and evolution from the patient's original conventional (acinar) prostatic adenocarcinoma (Figs 2E and 2F).
Next-generation sequencing. (A) Copy-number profile from the abdominal wall nodule highlighting the TMPRSS2 ERG locus break, a PTEN homozygous deletion, and a CDKN2A homozygous deletion. (B) Expression of androgen-responsive genes in the patient's second sample OncoSeq transcriptomics data. (C) Expression of neuroendocrine marker genes in the patient's second sample OncoSeq transcriptomics data. FPKM, fragments per kilobase of transcript per million mapped reads; LOH, loss of heterozygosity.
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Fig 3A). Fusions between the TMPRSS2 locus and Ets family transcription factors occur in nearly one half of prostate cancers in the United States and, to our knowledge, do not occur in other cancers. However, the transcriptomics data of the MI-OncoSeq platform showed low expression of the androgen receptor and androgen responsive genes KLK2, KLK3 (PSA), TMPRSS2, ACPP, and SLC45A3 (Fig 3B). However, expression of the neuroendocrine markers SYP, CHGA, CHGB, and NCAM1 were also low (Fig 3C).