Intraocular metastasis as a systemic presentation of neuroendocrine differentiation of prostate carcinoma.

A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE). His AV was very low in his RE, and in the eye fundus examination a mass without pigment was observed in the posterior pole with an adjacent exudative retinal detachment. Due to his personal history and results of the complementary tests such as ultrasound and magnetic resonance, the most likely diagnostic option was metastasis of prostate carcinoma, subsequently being confirmed with the histopathology results. Despite 4 cycles of chemotherapy, the patient did not show any clinical or radiological response, worsening until his death 3 months later.

Metástasis intraocular como presentación sistémica de un adenocarcinoma de próstata con diferenciación neuroendocrina / Intraocular metastasis as a systemic presentation of neuroendocrine differentiation of prostate carcinoma

Varón de 68 años derivado para valoración de una lesión amelanótica en el ojo derecho (OD) que asociaba como síntoma principal pérdida de agudeza visual (AV) progresiva de 2 meses de evolución. Entre sus antecedentes destaca un adenocarcinoma de próstata tratado con prostatectomía, linfadenectomía y radioterapia local (RT) coadyuvante hace 6 años. Asintomático hasta hace 6 meses, cuando se descubrió una metástasis en fémur izquierdo, tratada con radioterapia. La exploración del ojo izquierdo (OI) no tenía hallazgos de interés. En el OD su AV era muy baja y en el fondo de ojo (FO) se encontró una masa sin pigmento en polo posterior con un desprendimiento de retina (DdR) exudativo adyacente. Por sus antecedentes personales y características de las pruebas complementarias como ecografía o resonancia, la opción diagnóstica más probable era metástasis de adenocarcinoma de próstata, certificándose posteriormente con los resultados anatomopatológicos. A pesar de los 4 ciclos de quimioterapia (QT) recibidos, el paciente no obtuvo respuesta clínica ni radiológica, empeorando hasta su fallecimiento 3 meses después (AU)

A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE). His VA was very low in his RE, and in the eye fundus examination a mass without pigment was observed in the posterior pole with an adjacent exudative retinal detachment. Due to his personal history and results of the complementary tests such as ultrasound and magnetic resonance, the most likely diagnostic option was metastasis of prostate carcinoma, subsequently being confirmed with the histopathology results. Despite 4 cycles of chemotherapy, the patient did not show any clinical or radiological response, worsening until his death 3 months later (AU)

Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours. / Estudio inmunohistoquímico de los factores de trancripción de desarrollo neural (TTF1, ASCL1 y BRN2) en los tumores neuroendocrinos de próstata.

OBJECTIVE: Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate. MATERIAL AND METHODS: We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours. RESULTS: In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3. CONCLUSION: The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets.

Carcinoma en tejido mamario ectópico axilar con diferenciación neuroendocrina: reporte de un caso / Carcinoma in ectopic axillary breast tissue with neuroendocrine differentiation: case report

Presentar un caso de carcinoma en tejido mamario ectópico axilar. Paciente femenina de 38 años de edad, quien consultó por aumento de volumen y nódulo en región axilar de un año de evolución y punción aspiración por aguja fina previa no diagnóstica. En la evaluación se observó mamas axilares bilaterales, palpando en la derecha tumor duro de superficie irregular, se realizó mamografía, C y biopsia por aguja gruesa. Por el diagnóstico de la biopsia por aguja gruesa, se practicaron estudios de extensión y se trató con neoadyuvancia y cirugía. El estudio histopatológico de la pieza quirúrgica concluyó carcinoma ductal infiltrante con patrón neuroendocrino y metástasis en 2 de 18 ganglios, recibió adyuvancia y se mantiene libre de enfermedad

A case of female patient 38 years of age, who consulted for increased volume and axillary node in a year of evolution and prior non-diagnostic FNA. The evaluation noted bilateral axillary breasts, feeling hard lump on the right an irregular surface, we performed mammography, PAAF and core needle biopsy. For the diagnosis of the biopsy needle, extension studies were performed and treated with neoadjuvant therapy and surgery. Histopathological examination of the surgical specimen concluded infiltrating ductal carcinoma neuroendocrine pattern and metastatic in 2 of 18 nodes, received adjuvant therapy and remains free of disease

Condrosarcoma de celulas claras con diferenciacion neuroendocrina: estudio de un caso / Clear cell condrosarcoma with neuroendocrine differentiation: Report of a case

Introducción: Presentamos un caso inédito en la literatura de un condrosarcoma esquelético, variedad de células claras con diferenciación neuroendocrina. Presentación del caso: Se trató de un paciente masculino de 56 años de edad, quien presentó una lesión localizada en cuerpos vertebrales L1, L2, L3, con extensión a tejidos blandos. Posteriormente se observaron lesiones metastásicas en ambos campos pulmonares. Histológicamente se trató de una lesión lobulada, con células claras y escasa matriz extracelular de aspecto condroide. Los estudios inmunohistoquímicos demostraron positividad para proteína S-100, enolasa neuronal específica y antígeno de membrana epitelial. Conclusión: La diferenciación neuroendocrina ha sido descrita en condrosarcoma mixoide extraesquelético. Este caso es único en la literatura de condrosarcoma de células claras con difererenciación neuroendocrina.

We described a case of skeletal clear-cell chondrosarcoma with neuroendocrine differentiation. Case: A male 56-year old patient with a mass in L1, L2, L3 vertebral body, with extension to the soft tissues, and metastasis to both lungs. Histologically, the tumor structure was a lobullated mass, with medium size clear cells and scanty extracelular chondroid matrix. Immunohistochemical studies showed positivity for S-100 protein, neuron specific enolasa and epithelial membrane antigen. Conclusions: Evidence of extraskeletal chondrosarcoma with neuroendocrine features was described. Here, we present a unique case of clear-cell chondrosarcoma with neuroendocrine features.

Diferenciación neuroendocrina y marcadores de proliferación celular en adenocarcinoma de próstata en un grupo de casos con antígeno prostático específico normal vs elevado / Neuroendocrine differentiation and markers of cell proliferation in a group of patients with prostate adenocarcinoma and normal or high serum prostate-specific antigen levels

Objetivo. Investigar la población de células neuroendocrinas y sus características morfológicas en pacientes con cáncer de próstata y antígeno sérico normal versus antígeno sérico elevado. Material y métodos. En 13 años se identificaron 372 casos de cáncer de próstata de los cuales 19 (5.1%) con antígeno sérico normal (Grupo I). Se seleccionaron 16 grupos controles con antígeno sérico elevado y características histopatológicas similares (Grupo II). Se evaluaron porcentaje de necrosis tumoral, invasión vascular y perineural, inmunohistoquímica: sinaptofisina, enolasa neuroespecífica, antígeno prostático específico, Ki-67 y p53. Resultados. En el grupo I, se obtuvieron 61 % de casos positivos para antígeno tisular, 28.6 % sinaptofisina, 7.1 % para enolasa neuroespecífica, 50 % para p53 y 78.6 % para Ki-67. En el grupo II, los resultados fueron: sinaptofisina 13.3%, enolasa-neuroespecífica 26.6%, antígeno tisular 93%, p53 46.6% y Ki-67 66.7%. Con punto de corte de antígeno tisular expresado en < 80% de células neoplásicas, en el grupo I se encontraron 69.2% de casos, y en el grupo II 21.4% (p = 0.02). Conclusiones. El único dato histológico que mostró diferencia significativa fue la expresión tisular de antígeno prostático específico en < 80% de las células neoplásicas en el grupo I. Se asoció el incremento de las células neuroendocrinas con el menor número de células productoras de antígeno tisular; esta situación podría ser más visible al estudiar un mayor número de pacientes con características semejantes.

OBJECTIVE: Study the morphologic characteristics of neuroendocrine cells in prostate cancer with normal versus elevated prostate specific antigen (PSA). MATERIALS AND METHODS: 372 cases of prostate cancer were identified during a 13 year period, of which 19 displayed normal PSA (group I). Sixteen controls with elevated PSA and similar histopathological characteristics (group II) were included. We studied the degree of tumor necrosis, vascular and perineural invasion. Synaptophysin (SP), neuron specific enolase (NSE), PSA, Ki-67 and p53 inmunoreactivity were also analyzed. RESULTS: Group I positive findings were 61% PSA, 28.6% SP. 7.1% NSE, 50%p53, and 78.6% Ki-67. Group II positive findings were 93% PSA, 13.3% SP, 26.6% NSE 46.6% p53, and 66.7% Ki-67. When we used a <80% cut off point for PSA immunoreactivity in tumor cells, 69.2% of group I and 21.4% of group II were found. CONCLUSIONS: The sole histopathological finding that showed statistical significance was the tissular expression of the specific prostatic antigen in 80% of neoplasic cells in group I. The increase of neuroendocrine cells was associated with a smaller number of tissular antigen producing cells, a finding that could be more apparent if we were to study a larger sample size.