[Experience with sunitinib in hormone-resistant metastatic prostate cancer that is unresponsive to docetaxel]. / Experiencia con sunitinib en cáncer de próstata metastásico hormonorresistente sin respuesta a docetaxel.

INTRODUCTION: systemic treatment options for patients with hormone-refractory prostate cancer (HRPC) that progress despite the use of Docetaxel are very limited. One of the options of compassionate use currently available is the use of Sunitinib. We present a joint preliminary experience with the use of Sunitinib in this clinical case. PATIENTS AND METHODS: a series of eight cases is presented, which sets forth a prospective multicentre experience with Sunitinib in patients with hormone-refractory metastatic and progressive prostate cancer, previously treated with at least a regime of Docetaxel-based chemotherapy. Other alternative chemotherapy regimes had already been tried in some patients. The primary objective of our study was the PSA response rate and our secondary objective was the progression-free period. We administered a dosage of 50mg/day for four-week cycles, followed by a two-week rest per cycle, until we reached a total of eight cycles or up to clinical progression or intolerable toxicity. RESULTS: in four cases, the PSA dropped to below 50% of the baseline level at the beginning of the treatment, and five patients presented some decrease in PSA. The progression-free time was 16.4 weeks. Toxicity arising from the treatment was moderate and manageable. CONCLUSIONS: despite the limits of this experience, we can say that Sunitinib appears to be an active and safe option in patients with hormone-refractory prostate cancer that is resistant to chemotherapy with Docetaxel.

Experiencia con sunitinib en cáncer de próstata metastásico hormonorresistente sin respuesta a docetaxel / Experience with sunitinib in hormone-resistant metastatic prostate cancer that is unresponsive to docetaxel

Introducción: las opciones de tratamiento sistémico para los pacientes con cáncer de próstata hormonorrefractario (CPHR) que progresan a pesar del uso de docetaxel son muy limitadas. Una de las opciones de uso compasivo disponibles en la actualidad es el empleo de sunitinib. Presentamos una experiencia preliminar conjunta con el uso de sunitinib en esta circunstancia clínica. Pacientes y métodos: se presenta una serie de 8 casos que refleja una experiencia multicéntrica prospectiva con sunitinib en pacientes con cáncer de próstata metastático, hormonorrefractario y en progresión, previamente tratados con al menos un régimen quimioterápico a base de docetaxel. En algunos pacientes ya se habían ensayado otros regímenes quimioterápicos alternativos. El objetivo primario de nuestro estudio fue la tasa de respuesta de PSA, y el objetivo secundario el tiempo libre de progresión. Se administró una dosis de 50mg/ día durante ciclos de 4 semanas, seguidos de 2 semanas de descanso por ciclo, hasta alcanzar un total de 8 ciclos o hasta la progresión clínica o toxicidad intolerable. Resultados: en 4 casos el PSA descendió por debajo del 50% del nivel basal al inicio del tratamiento, y 5 pacientes presentaron algún descenso del PSA. El tiempo libre de progresión fue de 16,4 semanas. La toxicidad derivada del tratamiento fue moderada y manejable. Conclusiones: a pesar de lo limitado de esta experiencia, podemos decir que sunitinib parece una opción activa y segura en pacientes con cáncer de próstata hormonorrefractario y resistente a quimioterapia con docetaxel (AU)

Introduction: systemic treatment options for patients with hormone-refractory prostate cancer (HRPC) that progress despite the use of Docetaxel are very limited. One of the options of compassionate use currently available is the use of Sunitinib. We present a joint preliminary experience with the use of Sunitinib in this clinical case. Patients and methods: a series of eight cases is presented, which sets forth a prospective multicentre experience with Sunitinib in patients with hormone-refractory metastatic and progressive prostate cancer, previously treated with at least a regime of Docetaxel-based chemotherapy. Other alternative chemotherapy regimes had already been tried in some patients. The primary objective of our study was the PSA response rate and our secondary objective was the progression-free period. We administered a dosage of 50mg/day for four-week cycles, followed by a two-week rest per cycle, until we reached a total of eight cycles or up to clinical progression or intolerable toxicity. Results: in four cases, the PSA dropped to below 50% of the baseline level at the beginning of the treatment, and five patients presented some decrease in PSA. The progression-free time was 16.4 weeks. Toxicity arising from the treatment was moderate and manageable. Conclusions: despite the limits of this experience, we can say that Sunitinib appears to be an active and safe option in patients with hormone-refractory prostate cancer that is resistant to chemotherapy with Docetaxel (AU)

Encapsulated apocrine papillary carcinoma of the breast: case report with clinicopathologic and immunohistochemical study.

We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50-year-old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine-needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP-15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast.

Soft-tissue osteosarcoma with prominent aneurysmatic bone cyst-like features: a case report.

We describe the cytological features of a soft-tissue high-grade spindle and pleomorphic sarcoma. The smears showed hypercellularity composed of pleomorphic round and elongated cells, and a striking population of multinucleated osteoclast-type giant cells. Microscopically the tumor showed multiple patterns such as highly cellular pleomorphic, less cellular, and hyalinized areas with neoplastic cartilage and osteoid, and areas with hemorrhage and multicystic appearance with numerous osteoclastic giant cells, resembling aneurysmal bone cysts. Immunohistochemical studies showed positivity for vimentin, while chondroid tissue was positive for S-100, and osteoclastic giant cells stained positively for CD68. Due to the varied microscopic patterns, the differential diagnosis included many tumors containing osteoclastic giant cells and osteochondroid tissue.

Vascular adrenal pseudocyst: cytologic and immunohistochemical study.

Adrenal vascular cysts are rare lesions that might be considered in the differential diagnosis of adrenal tumors. Their origin is not clear. We report the clinicopathological findings of a large adrenal hemorrhagic pseudocyst (AHP) in a 73-yr-old man who complained of abdominal pain. An abdominal CT showed a 9 cm tumor in the left adrenal. A fine-needle aspiration biopsy (FNAB) was hemorrhagic and inconclusive. The tumor was excised and touch imprints were taken showing groups of spindled and fusiform cells with elongated nuclei, without atypia. Histologically, the tumor was well delimited by a fibrous capsule and contained numerous cystic spaces lined by endothelial cells and filled with erythrocytes, fibrin thrombus, and necrotic debris. Immunohistochemical study showed strong positivity for factor VIII-RA, CD31, and CD34. Also, the remaining adrenal showed a prominent frame of thin and medium caliber vessels, supporting a vascular origin for this entity. This case illustrates the difficulty in making a diagnosis by FNA and to keep in mind AHP when hematic aspirates are obtained from an adrenal tumor mass.

Giant adrenal cortical carcinoma, clinically "nonfunctional": report of a case containing cytoplasmic hyaline globules of vimentin.

Adrenal cortical carcinoma (ACC) is a rare neoplasm that affects all age groups, with a bimodal peak of incidence, in young individuals in the first decade or two of life and in older subjects in the fifth to seventh decades. It may be clinically "functional" with Cushing's syndrome, virilization, or feminization, or it may be "nonfunctional." We report on the case of a 42-yr-old woman who complained of abdominal pain and a large adrenal tumor measuring 20 cm in size. No endocrine symptoms were observed. Laboratory tests showed increased levels of adrenocorticotropic hormone (ACTH), serum cortisol, and urinary free cortisol. Cytohistologic features were typical of ACC. A striking presence of hyaline cytoplasmatic globules was seen in cytologic smears and histologically, being immunoreactive for vimentin, consistent with an intracellular store of intermediate filaments. The tumor showed high proliferative activity (40%) with Ki-67 and negativity for p53, cerbB2, and bcl-2. Although hyaline globules are more frequent in pheochromocytomas and other neoplasms, they may also be present in ACC. These globules may be observed in cytologic smears. Also, the identification and immunohistochemical characterization of these hyaline globules in metastases may be useful in determining the origin of primary occult tumors. Diagn. Cytopathol. 1999;21:394-397.

Multicentric oncocytoma of the lung diagnosed by fine-needle aspiration.

A 50-yr-old man presented with dyspnea. On chest X-ray, multiple pulmonary nodules were observed. Fine-needle aspiration biopsy (FNAB) showed tridimensional aggregates of atypical round epithelial cells, containing numerous cytoplasmic granules. The tissue fragment confirmed the presence of an epithelial tumor composed of trabecular sheets of clear cells, with numerous cytoplasmic granules which stained with phosphotungstic acid hematoxylin (PTAH). Immunohistochemically, the tumor cells were positive for cytokeratins and antimitochondrial antigen, whereas chromogranin, synaptophysin, S-100 protein, and HMB-45 were negative. Clinical and tomographic studies ruled out any tumor mass elsewhere. The rarity of this lesion in the lung and the potential difficulties for its diagnosis prompted us to report the clinical, cytological, and immunohistochemical findings in this case.

Giant cell carcinoma of the lung. Report of a case with cytohistologic and clinical correlation.

BACKGROUND: Giant cell carcinoma (GCC) of the lung is an unusual tumor characterized by an aggressive outcome. CASE: A peripheral lung tumor was observed in an elderly male. At presentation the clinical symptoms were cough, thoracic pain and hemoptysis. Chest roentgenography showed a left pleural effusion and neutrophilia in the blood. Bronchoscopic examination showed a peripheral tumor mass that could not be biopsied. Bronchoalveolar lavage was negative. The patient underwent a cerebrovascular accident and died. The autopsy showed a peripheral giant cell tumor of the left lung that involved regional and mediastinal lymph nodes. Touch imprints showed tridimensional clusters of pleomorphic and large cells, some of which were multinucleated, containing leukocytes in their cytoplasm. CONCLUSION: This case illustrates the typical cytohistologic features of GCT of the lung, which should be considered in the differential diagnosis of any peripheral lung tumor composed of large cells. Clinical correlation is helpful in reaching the correct diagnosis.

Nodular fasciitis of the vulva. Report of a case with immunohistochemical study.

Nodular fasciitis (NF) is a tumor-like condition composed of fibroblasts and myofibroblasts, usually located in the subcutaneous tissue of the extremities. Histologically, it can mimic a myogenic sarcoma because of its hypercellularity, brisk mitotic rate and the presence of actin. NF of the vulva is rare with only eleven cases reported in the English literature. A 40 year-old woman developed a nodule in labium majus that was surgically excised. Microscopical examination revealed a typical example of NF with occasional multinucleated giant cells. The immunohistochemical study showed positivity for vimentin and muscle-specific actin in the spindle cells. The multinucleated cells stained with CD68. MIB-1 was positive in less than 5% of the cells which indicated a low proliferative activity. The patient has been followed for 5 years and no relapses occurred. The rarity of this lesion in the vulva and the potential difficulties for its diagnosis led us to report the clinical and immunohistochemical study of this case.

Intramammary lymph node involvement by mycosis fungoides diagnosed by fine-needle aspiration biopsy.

We report on a case of a patient with diagnosis of mycosis fungoides (MF) who subsequently developed enlargement of the intramammary lymph nodes, which were demonstrated to be involved by tumor on fine-needle aspiration (FNA) cytology. The patient was a 66-yr-old female who had recently noticed the appearance of circumscribed bilateral breast nodules. A mammographic study showed clearly outlined nodules of low density. FNA showed atypical small and large lymphocytes with cerebriform appearance, consistent with intramammary lymph node infiltration by MF. To our knowledge this is the first report of intramammary palpable lymph nodes involved by MF and confirmed by FNA. This case provides support for the use of fine-needle aspiration biopsy as an accurate method for staging MF successfully.

Breast carcinoma with endocrine features. Report of a case with cytologic and immunohistochemical studies.

BACKGROUND: Endocrine differentiation in breast cancer in females is uncommon and well established, while only rare articles reported the cytologic features. CASE: Invasive ductal carcinoma of the breast with endocrine features occurred in an 83-year-old female. The aspirates were hypercellular, containing many cohesive aggregates of uniform, round cells with central nuclei and granular cytoplasm intermixed with fine capillary vessels. The subsequent mastectomy specimen contained a well-delimitated tumor mass measuring 2.5 cm in diameter. Microscopically the tumor was formed by a typical solid and organoid pattern of growth. Immunohistochemical study showed positivity for estrogen and progesterone receptors, cytokeratins and chromogranin. None of 10 axillary lymph nodes contained metastasis. The patient was well seven months after surgery. The cytologic features encompassed signs of endocrine differentiation. CONCLUSION: This case illustrates the clinicopathologic features of a ductal infiltrating carcinoma with endocrine features and renders the clues to cytologic diagnosis with accuracy on fine needle aspiration.

Adenomyoepithelioma of the breast: report of two cases with prominent cystic changes and intranuclear inclusions.

Adenomyoepithelioma is a rare breast tumor. Histologically it may disclose different patterns of growth, and some additional features may result in diagnostic errors. We describe 2 cases of adenomyoepithelioma of the breast initially examined by fine-needle aspiration biopsy (FNAB). Cytologic features included hypercellularity, clusters of epithelial and myoepithelial cells with occasional intranuclear inclusions, prominent apocrine metaplasia, and foam cells. Histologically, both tumors were diagnosed as adenomyepithelioma tubular-variant, with prominent myoepithelial clear cells, apocrine metaplasia, and foci of squamous metaplasia. Immunohistochemically, the tumors showed strong positivity for keratins CAM 5.2, AE1/AE3, and EMA in the epithelial component, while the myoepithelial cells reacted with muscle-specific actin (A14 and HHF35) and S-100 protein. We point out that FNAB in this rare tumor may exhibit a varied spectrum of cells that may result in confusion with other lesions, and we call attention to the presence of intranuclear inclusions. The latter observation in the present cases by cytologic and histologic assessment provides and additional feature to the morphological characteristics of adenomyoepithelioma of the breast.

Cellular proliferation in breast ductal infiltrating carcinoma. Correlation with clinical and histopathological variables.

To evaluate four methods to study cellular proliferation (mitotic count, mitotic index, PCNA and MIB1) in a series of breast ductal invasive cancer NOS, and the possible correlations between these different methods and other pathological variables, we studied 110 ductal invasive carcinomas NOS specimens. Mitoses per 1000 tumor cells and per 10 HPF, and immunostaining for PCNA and MIB1 were evaluated. Other accepted prognostic factors such as tumor size, histologic grade, estrogen and progesterone receptors measured by immunostaining and axillary status were obtained. Correlation between the four methods to evaluate cellular proliferation and these other variables was performed. Mitotic count, mitotic index, PCNA and MIB1 showed a good rate of correlation (r = 0.71-0.53, p < 0.05), with the exception of MIB1-mitotic index which was weak (r = 0.38, p < 0.05). A strong association between cellular proliferation, with independence of the method applied, and histologic grade, ER and PR was obtained. No association was observed with tumor size and lymph node involvement. In conclusion, there was a strong correlation between the four methods to evaluate cellular proliferation. Mitotic count (per 10 HPF) and MIB1 show a better correlation with other morphological variables. None of the evaluated methods are associated with the tumor size and axillary status, suggesting that mitotic count is the most accurate method to analyse cellular proliferation in routine practice.

Adenoma of thyroid gland containing fat (thyrolipoma). Report of a case.

Thyroid adenomas containing adipose tissue are rare. Only scattered case reports have been recorded. We describe an additional case of an adenolipoma of the thyroid gland, incidentally found in residual gland subsequent to excision of a papillary carcinoma.

Microvessel quantitation in breast ductal invasive carcinoma. Correlation with proliferative activity, hormonal receptors and lymph node metastases.

To investigate the correlation between tumor angiogenesis with axillary metastasis in breast cancer, we analyzed a series of 130 cases of infiltrating ductal carcinoma N.O.S. Tissue sections were stained with factor VIII-RA and microvessel quantitation was performed at x 400 magnification in the most vascular areas and expressed in vessels per mm2. Other variables such as tumor size, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, anti-P.C.N.A. (proliferative cell nuclear antigen) and estradiol and progesterone receptors measured by an immunohistochemical method were determined. Statistical analysis of variance (AN-OVA) and Pearson's correlation coefficient were applied. The average of vessels per mm2 in tumors with metastases (n = 70) was 82.0 (median 74, SD 37.5), whereas in tumors without metastases (n = 60), it was 67.1 (median 64, SD 28.1). The difference was statistically significant (p < 0.01). However, the significance was lost when tumor size was introduced as a co-factor in a multifactorial analysis of variance. The number of vessels was unassociated with menopausal status, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, estradiol and progesterone receptors and proliferative activity measured with anti-P.C.N.A. We conclude that in breast ductal invasive carcinoma, when tumor size is taken into consideration, angiogenesis is not associated with axillary lymph node metastases.