A Rare Case of BRCA2 Squamous Cell CarcinomaAjay Mohinani MSIII, Sujith Kalmadi MD, Jennifer Thompson FNP-C, Pratik Patel MD, William Peppo DO

Midwestern University- Arizona College of Osteopathic Medicine, Arizona State Urological Institute,Ironwood Cancer & Research Centers

Case Report

A 56-year-old previously healthy Caucasian male was referred from urology for a 6 week history of having a weak urinary stream which progressed to the point of no urination but denied hematuria, dysuria or nocturia. He was seen by urology due to no urine output and was subsequently catheterized. Past medical history includes hypospadias repair as a child.

Family history includes father deceased from gastric cancer, younger brother with liposarcoma and maternal grandmother with breast cancer.

Trans rectal ultrasound showed nodularity and fine needle aspiration biopsy confirmed SCC in 9 out of 12 biopsies with urothelial differentiation (Fig 1, Table 1).

PET/CT with contrast of the chest, abdomen and pelvis was performed for staging purposes and showed a prostatic mass extending toward the bladder and the presence of multiple peripheral lung nodules. Lung biopsy confirmed metastatic SCC. Genetic testing confirmed presence of BRCA 2 mutation.

As there is no squamous epithelium in the prostate, the origin was determined to be the prostatic urethra with extension into the prostate (Figure 2).

The patient was started on dose dense Methotrexate, Vinblastine, Adriamycin, Cisplatin (MVAC) with remission of disease. Maintenance immunotherapy using Pembrolizumab (Keytruda) was then used with continued remission (Figure 3) but led to unrelated SCC of the scalp and subsequent treatment with Mohs procedure.

The patient had recurrence of disease 20 months later and treatment with Poly ADP Ribose Polymerase (PARP) inhibitors was recommended given underlying mutation and unique presentation.

Pt. continues to be treated with Niraparib 27 months from diagnosis. He had restoration of normal sexual activity but continued inability to urinate and suprapubic catheter is still in place. Patient is doing well 27 months from diagnosis..

Treatment & Management

Management of metastatic prostatic adenocarcinoma involves Gleason score staging and treatment with LHRH agonist therapy in combination with oral hormonal modulation therapy.

BRCA 2 mutations have been associated with worse prognosis due to greater lymph node involvement and distant metastasis compared to non BRCA 2 mutations. However, these mutations are known to respond well to chemotherapy, although most trials have studied adenocarcinomas.

The patient’s previous history of hypospadias increases the risk of testicular cancer but no evidence exists for an increased risk of urethral/prostatic SCC. Only one case has been reported in the distal urethra in a patient with hypospadias.

Discussion

References

Introduction

BRCA 2 mutations in men have been known to increase the risk of breast and prostatic adenocarcinoma but this case presents the clinical course of a patient with a BRCA 2 mutation who presented with squamous cell carcinoma (SCC) of the prostate. Staging and treatment differs between adenocarcinoma and SCC of the prostate. The prostate is composed of columnar glandular epithelium only and Gleason score is used to stage prostatic adenocarcinoma so the presence of SCC in the prostate posed a unique challenge in the management of this patient.

It was determined prostatic SCC with urothelial differentiation would benefit from chemotherapy targeted at the urothelial differentiation. Studies have shown the MVAC and Pembrolizumab combination to be effective in the treatment of urothelial carcinomas.With disease recurrence, PARP inhibitors was chosen due to effectiveness against known BRCA2 cancers.

This case was rare due to the unusual location and presentation of a BRCA2 cancer along with the delay in symptoms the patient experienced. At presentation, the patient had stage IV metastatic SCC. The prognosis for metastatic SCC is dismal with a median survival of 14 months and a 3 year survival of 9%.

Unconventional methods had to be used to target the cancer. MVAC therapy targets urothelial carcinoma of the bladder and was thus used as induction chemotherapy followed by Pembrolizumabimmunotherapy. This led to remission with a significant decrease in size of prostatic mass and pelvic lymphadenopathy.

Due to recurrence and underlying BRCA2 mutation, Niraparib therapy was started and patient was able to return to work and restore quality of life 27 months from diagnosis.

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6. Sandhu SK, Schelman WR, Wilding G, et al. The poly(ADP-ribose) polymerase inhibitor niraparib(MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial.Lancet Oncol. 2013;(9):882-92

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Location PathologyRight Base Squamous Cell Carcinoma

Right Mid Squamous Cell Carcinoma

Right Apex Squamous Cell Carcinoma

Right Lateral Base Squamous Cell Carcinoma

Right Lateral Mid Squamous Cell Carcinoma

Right Lateral Apex Squamous Cell Carcinoma

Left Base Benign Prostate Tissue

Left Mid Squamous Cell Carcinoma

Left Apex Squamous Cell Carcinoma

Left Lateral Base Benign Prostate Tissue

Left Lateral Mid Benign Prostate Tissue

Left Lateral Apex Squamous Cell Carcinoma

Conclusion

Table 1. Prostate biopsy results by location.

Figure 1. Prostate biopsy, Red-SCC; Green- Benign

Discussion

Figure 2 (top) and 3 (bottom): PET scans showing extent of prostate involvement at diagnosis (Fig 2) and subsequent remission following MVAC and Pembrolizumab treatment (Fig 3).

Excretion of dye via prostatic urethra

Uptake of dye into cancerous cells