Download Uncommon presentation of prostate cancer with neuroendocrine

CASE CLINICAL
Uncommon presentation of prostate
cancer with neuroendocrine
differentiation
Santana-Ríos Zael, Fulda-Graue Santiago, Pérez-Becerra Rodrigo, Urdiales-Ortiz Alejandro, Morales-Montor
Jorge, Pacheco-Gahbler Carlos, Calderón-Ferro Francisco.
178
•ABSTRACT
•RESUMEN
Neuroendocrine differentiation (NED) in prostate cancer
has gained in importance due to its prognostic and
therapeutic implications. Some authors have related
NED degree with poor cellular differentiation, disease
progression and androgen-independence.
La diferenciación neuroendocrina en el cáncer de próstata
ha cobrado importancia por las implicaciones pronósticas
y terapéuticas. Algunos autores han relacionado el grado
de diferenciación con pobre diferenciación celular, progresión e independencia a andrógenos.
Objective: The case of a patient diagnosed with prostate
cancer in remission with neuroendocrine differentiation
and multiple metastatic disease is presented.
Objetivo: Presentar el caso de un paciente con diagnóstico de cáncer de próstata en remisión, con diferenciación
neuroendocrina y enfermedad metastásica múltiple.
Clinical case: The 78-year-old patient presented with
prostate adenocarcinoma, Gleason 4+4, 79ng/ml initial
PSA and positive scintiscan in May, 2003 (T2bN0M1).
He received anti-androgen hormonal treatment and
underwent orchiectomy. Patient went into clinical
remission with 0.0ng/ml PSA in June 2004 and so
antiandrogen was suspended. In January 2008, patient
presented with intestinal obstruction and 1.7ng/ml PSA.
He underwent exploratory laparoscopy which revealed
hepatic nodules and prostate-dependent pelvic mass
infiltrating bladder and rectum. Diversion colostomy
was performed. Progression was not favorable and the
patient died 5 days later. Post-mortem histopathological
report stated prostate adenocarcinoma, Gleason 5+5,
significant neuroendocrine differentiation and rectum
and bladder invasion.
Caso clínico: Paciente del sexo masculino de 78 años de
edad que cursó con adenocarcinoma de próstata, Gleason 4+4, antígeno prostático específico inicial de 79ng/
mL y gamagrama óseo positivo en mayo de 2003 (T2bN0M1). El paciente recibió tratamiento hormonal con
fármacos antiandrogénicos y se le practicó orquiectomía. Presentó remisión del cuadro clínico, documentada por medio de: antígeno prostático específico de 0.0
ng/mL en junio 2004, lo que motivó suspender el tratamiento antiandrogénico. En enero de 2008 ingresó al
servicio por presentar obstrucción intestinal, la determinación de antígeno prostático específico fue de 1.7 ng/
mL. Se le practicó laparotomía exploradora encontrando
nódulos hepáticos, masa en pelvis dependiente de próstata con infiltración a vejiga y recto. Se le realizó colostomía derivativa. La evolución no fue favorable y falleció
Urology and Pathological Anatomy Divisions, Dr. Manuel Gea
González General Hospital, Mexico City.
Corresponding author: Dr. Zael Santana Ríos. Lorenzo Rodríguez No.
77 Colonia San José Insurgentes, Benito Juárez 03900, México, D.F.
Telephone: 91162104. Cell Phone: 04455-5433-2683. Email:
zaelsantanar@yahoo.com
Rev Mex Urol 2009;69(4):178-180
Santana-Ríos Z, et al Uncommon presentation of prostate cancer with neuroendocrine differentiation
Discussion: Prostate cancer patients with high NED
marker levels (chromogranin A) appear to have poor
prognosis and can present with poorly differentiated,
hormone-resistant tumors. In long-term anti-androgen
treatment there is an elevation of neuroendocrine cells,
suggesting that hormonal deprivation accelerates the
process.
Conclusions: Neuroendocrine differentiation is related
to poor prostate cancer prognosis.
Key words: Neuroendocrine differentiation, chromogranin
A, prostate cancer, Mexico.
5 días después. En el reporte histopatológico postmortem
reportó adenocarcinoma de próstata, Gleason 5 + 5 y diferenciación neuroendocrina importante, invasión a recto
y vejiga.
Discusión: Se ha observado que los pacientes con cáncer de próstata con niveles altos de marcadores de diferenciación neuroendocrina (cromogranina A), tienen peor
pronóstico y pueden ser tumores poco diferenciados y
hormono-resistentes. En el tratamiento a largo plazo con
fármacos antiandrogénicos se eleva la presencia de células
neuroendocrinas, lo que sugiere que la deprivación hormonal acelera el proceso.
Conclusiones: La diferenciación neuroendocrina se relaciona con mal pronóstico en cáncer de próstata.
Palabras clave: Diferenciación neuroendocrina, cromogranina A, cáncer de próstata, México.
•BACKGROUND
Prostate cancer (CaP) is the most frequently diagnosed
malignant neoplasia in men. Its natural history is mainly
influenced by factors such as clinical stage and tumor
differentiation grade. Prognosis is good, with or without
treatment, when CaP is detected in the early stages and
is low grade, unlike advanced stage CaP with a high
differentiation grade.
Neuroendocrine differentiation (NED) has become
more important due to its prognostic and therapeutic
implications.1,2 Neuroendocrine (NE) cells have a
regulatory function in growth, cellular differentiation
and other biological processes. Chromogranin A is
very useful in the characterization of neuroendocrine
tumors. The degree of NED has been associated with
poor cellular differentiation, disease progression and
androgen-resistance.3-5
of 79 ng/ml. During physical examination the distended
abdomen was painful upon palpation, but with no signs
of peritoneal irritation. Digital rectal examination (DRE)
revealed empty rectal ampulla and grade III prostatic
growth of soft consistency with T2b staging. Ultrasoundguided transrectal prostate biopsies were carried out
reporting prostate adenocarcinoma with Gleason 4+4=8
in 9/9 fragments. Bone scintiscan was positive for
metastatic disease in L1-L5 and sternum. Treatment was
initiated with maximum androgen blockade with simple
bilateral orchiectomy and the anti-androgen, flutamide.
Obstructive symptomatology deteriorated into
acute urinary retention (AUR), requiring transurethral
resection of the prostate (TURP). Histopathological
report stated adenocarcinoma, Gleason 3+4=7 and
control PSA of 2.7ng/ml.
•CLINICAL CASE
Patient discontinued follow-up for 3 years until
current hospital admittance for intestinal obstruction
associated with macroscopic hematuria.
The patient is a 78-year-old man with a family history
of CaP (father), a history of high blood pressure of
3-year progression, smoking and serious alcoholism.
He sought medical attention at the emergency room
for intense abdominal pain, abdominal distension
and constipation, all of 48-hour progression. Patient
presented with obstructive urinary symptomatology of
5-year progression, an IPSS of 25 points and initial PSA
Obstructive symptoms persisted and patient showed
clinical decline. Exploratory laparotomy was performed
revealing enlarged mesenteric lymph nodes, multiple
Intestinal obstruction was managed conservatively
but it persisted. Abdominal tomography was ordered
which showed images suggestive of metastatic disease
in liver and retroperitoneum as well as an obstructive,
heterogeneous prostate with increase in volume.
Rev Mex Urol 2009;69(3):178-180
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Santana-Ríos Z, et al Uncommon presentation of prostate cancer with neuroendocrine differentiation
hepatic nodules, tumor mass in the iliac fossa with
infiltration into the bladder and rectum. There was
almost total obstruction of the rectal opening and so
diversion colostomy was carried out.
After surgery, there was progressive general
deterioration resulting in cardiac failure, renal insufficiency,
respiratory insufficiency, abdominal distension and refractory shock. The patient responded poorly to treatment
with vasoactive amines and died 4 days later.
Autopsy report described poorly differentiated
prostate adenocarcinoma with a Gleason 5+5 pattern
and neuroendocrine differentiation (NED) with bladder
and rectum invasion. It also reported metastases to
periaortic, peritrachael-bronchial and peripancreatic
lymph nodes, liver, gall bladder, lung, vertebra and rib.
•DISCUSSION
Neuroendocrine cells have been identified in up to
92% of prostatic tissue. However, it has been observed
that higher levels of NED markers in CaP patients may
be due to tumors that are poorly differentiated, hormone
resistant and with poor prognosis. Since NED is
more frequently seen in poorly differentiated tumors,
some authors question its association with poor prognosis
considering them to be independent factors.6 A greater
number of neuroendocrine cells have been observed
after hormone deprivation and long-term androgen
blockade (since this can reduce enzyme degradation
of neuroendocrine products), suggesting that hormone
deprivation may speed up the NED process.7
180
Rev Mex Urol 2009;69(4):178-180
•CONCLUSIONS
Neuroendocrine differentiation in prostate cancer
is associated with poor prognosis, tumor differentiation
grade and clinical stage. It is also thought that androgen
blockade can activate disease progression, extension
and dissemination (from the increase in the number of
neuroendocrine cells). The relation observed among
neuroendocrine differentiation, metastasis and disease
extension is debatable.
Therefore it is necessary to continue to analyze
the direct association between prostate cancer and
neuroendocrine differentiation in order to establish
early therapeutic strategies and to predict prognosis.
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