Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy.

BACKGROUND: Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. OBJECTIVE: The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. MATERIAL AND METHODS: Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, ß-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. RESULTS: The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining ß-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94-159.8). CONCLUSION: Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapy.

Comparative study of the clinical, histological, and biological characteristics of squamous cell carcinomas in areas previously treated with photodynamic therapy.

Although photodynamic therapy (PDT) is an effective treatment option for non-melanoma skin cancer, the development of aggressive tumours in PDT-treated areas has been described. To evaluate the clinical, histological, and biological characteristics of squamous cell carcinomas (SCCs) in areas previously treated with PDT vs those arising in areas never treated with this therapeutic modality. A retrospective observational study was designed. We collected all cases of invasive SCCs in areas previously treated with PDT. The control group consisted of an equivalent number of SCCs randomly selected from the database of our pathology department. Expression of specific markers implicated in SCC progression, including p53, Ki67, COX-2, cyclin D1, E-cadherin, EGFR, survivin, and pERK, was analysed. A total of 699 patients were treated with PDT for non-melanoma skin cancer during the course of the study. Ten invasive SCCs arising in areas previously treated with methylaminolevulinate-PDT were diagnosed in six patients. The control group consisted of 10 invasive SCCs from 10 patients never treated with PDT. In the PDT group, the mean tumour size was significantly lower and the absence of ulceration was more frequent than in the control group (p<0.024 and p = 0.035, respectively). A diffuse survivin staining pattern was observed in 90% of tumours in the PDT group versus 50% in the comparative group (p = 0.141). The number of SCCs arising in areas previously treated with PDT was very low and did not differ significantly from that of SCCs developing in non-PDT-treated areas.

Imiquimod and Photodynamic Therapy Are Useful in the Treatment of Porokeratosis in Children with Bone Marrow Transplantation.

Porokeratosis is an uncommon disorder that affects keratinization. Immunosuppression may favor the development of porokeratotic lesions. Patients who receive allogenic transplants represent a therapeutic challenge to dermatologists. We report two cases of porokeratosis in children with bone marrow transplant and their excellent response to imiquimod and photodynamic therapy.

Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy.

Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.

Neuropeptide Y expression in cutaneous melanoma.

BACKGROUND: Neuropeptide Y (NPY) is widely found in the nervous system and has a role in numerous physiologic processes. In addition, NPY receptors are expressed in neuroendocrine tumors, breast cancer, prostate cancer, kidney cancer, and some types of sarcomas. Different neuropeptides, particularly α-melanocyte-stimulating hormone (MSH), seem to play a role in the pathogenesis of melanoma. OBJECTIVE: We sought to analyze the expression of NPY in cutaneous melanoma, its association with clinical and histologic features, and its correlation with α-MSH. METHODS: This was an observational study of the immunohistochemical expression of NPY and α-MSH in tissue samples of cutaneous melanomas, different types of melanocytic nevi, and melanoma metastases diagnosed from 2004 to 2008 in San Jorge Hospital, Huesca, Spain. RESULTS: A total of 184 lesions were studied: 49 primary cutaneous melanomas, 12 melanoma metastases (9 cutaneous and 3 lymphatic), and 123 melanocytic nevi. Immunostaining revealed that levels of NPY and α-MSH were significantly higher in melanomas than in melanocytic nevi (P < .001). Melanoma metastases were negative for both neuropeptides. Nodular melanomas showed the highest median percentage of NPY positive cells (75% [20-95]) followed by superficial spreading melanoma (25% [2-92]), whereas lentigo maligna were negative (0% [0-0]). Significant, direct associations between NPY expression and vertical growth (P = .0141) and presence of metastasis (P = .0196) were observed. NPY and α-MSH were positively correlated in cutaneous melanoma (0.49, P < .001). LIMITATIONS: The sample size of melanomas was not very large. CONCLUSION: Our study demonstrates that NPY is significantly expressed in melanomas, especially the nodular type, being associated with invasiveness independently of proliferative markers such as thickness, ulceration, and mitotic index.

Clear cell carcinoma of the ovary diagnosed in ascitic fluid. A case report.

BACKGROUND: Clear cell carcinoma of the ovary (CCC) is a rare variety of ovarian cancer. CASE: A case of CCC in a 49-year-old woman was diagnosed in asciticfluid on thin-layer preparations. Peritoneal fluid cytology revealed papillary clusters of cells with clear cytoplasm and extracellular hyaline material generally without neoplastic cells. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. CONCLUSION: CCC has a distinctive cytomorphologic appearance, and the entity may be diagnosed on ascitic fluid cytology.

Extraovarian primary peritoneal carcinoma. A case report

Se presenta un caso de carcinoma peritoneal primario extraovárico. Este raro e interesante tumor se caracteriza por una carcinomatosis peritoneal y por un patrón histológico similar al del carcinoma papilar seroso de ovario, pero sin comprometer o sólo afectando microscópicamente la superficie de los ovarios. La paciente presentaba hinchazón abdominal, ascitis con citología positiva y el CA-125 elevado en el suero. En el momento de la cirugía se encontró una afectación peritoneal difusa o multifocal, existiendo afectación microscópica de la superficie serosa ovárica. Las células tumorales fueron positivas para citoqueratina (AE1/AE3), antígeno de membrana epitelial, B72.3, Ber- EP4, Leu-M1, p53, antígeno carcinoembrionario, fosfatasa alcalina placentaria, proteína S-100, CA-125 y receptores estrogénicos

One case of extraovarian primary peritoneal carcinoma is reported. This rare interesting tumor is characterized by a peritoneal carcinomatosis with ascites and by a histological pattern similar to ovarian serous papillary carcinoma, but it either spares the ovaries or involves the surface of the ovaries only microscopically. The patient had abdominal swelling, ascites with positive cytology, and elevated serum CA-125. At surgery multifocal or diffuse peritoneal involvement was found. Microscopic ovarian serosal surface involvement was demonstrated. Tumor cells stained positive for cytokeratin (AE1/AE3), epithelial membrane antigen, B72.3, Ber-EP4, Leu-M1, p53, carcinoembryonic antigen, placental alkaline phosphatase, S-100, CA-125, and estrogen receptors

Primary pulmonary botryomycosis diagnosed by fine needle aspiration cytology: a case report.

BACKGROUND: Primary pulmonary botryomycosis is an uncommon suppurative bacterial infection of the lung. Cytologic findings by conventional methods and thin-layer preparations in1 case are presented. CASE: A 45-year-old man had primary pulmonary botryomycosis diagnosed by fine needle aspiration cytology (FNAC). Aspiration smears were characterized by densely packed microorganisms surrounded by polymorphonuclear leukocytes. Microbiologic analysis of cytologic material revealed colonies of Streptococcus constellatus. CONCLUSION: FNAC diagnosis of pulmonary botryomycosis offers the opportunity to distinguish this bacterial infection from lung cancer and avoid unnecessary surgery.

[Old schwannoma: a rare type of schwannoma]. / Schwannoma antiguo: variante rara de schwannoma.

OBJECTIVES: We report one case of retroperitoneal schwannoma with unfrequent histological characteristics evaluating its clinical significance and therapeutic options. METHODS: We report the case of a benign retroperitoneal schwannoma as an incidental MRI finding in a 70 year-old female patient with symptoms of lumbosciatic pain for 6 months. We perform a bibliographic review. RESULTS: After surgical excision the diagnosis was retroperitoneal old schwannoma. No additional treatment was given. There is no evidence of recurrence on follow-up. The histological changes apparent in the cases of old schwannoma have been interpreted as degenerative, indicating a long evolution, which has motivated its denomination as old. Some cases have been diagnosed as malignant. CONCLUSIONS: The old schwannoma is a rare variety of the benign common schwannoma. Microscopically its shows areas of hypocellular tissue and pleomorphic nuclei suggestive of malignancy. Therapeutic management is similar to other benign retroperitoneal processes, surgical excision and follow-up.

Schwannoma antiguo: variante rara de schwannoma / Old schwannomaa. a rare type of schwannoma

OBJETIVO: A propósito de un caso deschwannoma retroperitoneal con características histológicaspoco frecuentes, se evalúa su significación clínica eindicaciones de manejo terapeutico.MÉTODOS: Presentación de un caso de schwannomaretroperitoneal benigno, como hallazgo incidental, alpracticar una Resonancia Magnética, en una paciente de70 años cuya clínica era de una lumbociática de seismeses de evolución. Revisión bibliográfica.RESULTADOS: Tras la exéresis quirúrgica se llegó al diagnósticode schwannoma retroperitoneal antiguo. No seadministra ningún tratamiento complementario. No se haevidenciado recidiva durante seguimiento. Los cambioshistológicos que se ven en los casos de schawannomaantiguo se han interpretado como degenerativos, indicandouna larga evolución, que ha motivado su denominaciónde “antiguos”. Algunos de los casos fueron diagnosticadoscomo malignos.CONCLUSIONES: El schwannoma antiguo es una variantepoco habitual del schwannoma común benigno.Microscópicamente muestra áreas de tejido hipocelular ynúcleos pleomórficos sugestivos de malignidad. Su manejoterapéutico es similar al de otros procesos benginosretroperitoneales, mediante exéresis quirúrgica y seguimiento

OBJECTIVES: We report one case ofretroperitoneal schwannoma with unfrequent histologicalcharacteristics evaluating its clinical significance andtherapeutic options.METHODS: We report the case of a benign retroperitonealschwannoma as an incidental MRI finding in a 70-yearoldfemale patient with symptoms of lumbosciatic painfor 6 months. We perform a bibliographic review.RESULTS: After surgical excision the diagnosis wasretroperitoneal old schwannoma. No additionaltreatment was given. There is no evidence of recurrenceon follow-up. The histological changes apparent in thecases of old schwannoma have been interpreted asdegenerative, indicating a long evolution, which hasmotivated its denomination as old. Some cases havebeen diagnosed as malignant.CONCLUSIONS: The old schwannoma is a rarevariety of the benign common schwannoma.Microscopically its shows areas of hypocellular tissueand pleomorphic nuclei suggestive of malignancy.Therapeutic management is similar to other benignretroperitoneal processes, surgical excision and followup

Linfoma primario cutáneo anaplásico de células grandes CD30 (Ki-1) positivo simulando un sarcoma epitelioide / CD30 (Ki-1) primary cutaneous anaplastic large-cell lymphoma mimicking an epithelioid sarcoma

Presentamos un caso de linfoma primario cutáneo de células grandes CD30 (Ki-1) positivo con características histológicas que recuerdan a un sarcoma epitelioide. El linfoma primario cutáneo anaplásico de células grandes CD30 positivo es una entidad clinicopatológica recientemente descrita, reconocida por criterios inmunohistoquímicos. Describimos el caso de una mujer de 74 años de edad con un tumor ulcerado en el tronco, de 3 meses de evolución. El diagnóstico se hizo en base a los hallazgos inmunohistoquímicos. No se detectó afectación sistémica. La paciente está bien, sin enfermedad extracutánea concurrente, tras 6 años de seguimiento. Los estudios clínicos indican un mejor pronóstico en los linfomas cutáneos anaplásicos de células grandes CD30 positivos que en los linfomas anaplásicos de células grandes CD30 positivos nodales y que en los otros linfomas cutáneos anaplásicos de células grandes. Este es pues, un caso de regresión espontánea y seguimiento favorable en este tipo de linfomas cutáneos, que tiene unos rasgos morfológicos peculiares, como es su parecido morfológico con un sarcoma epitelioide (AU)

Dermal analogue tumor of the salivary gland diagnosed by fine needle aspiration cytology. A case report.

BACKGROUND: Dermal analogue tumor of the salivary gland is a rare form of salivary gland adenoma. Cytologic and histologic findings of 1 case are presented. CASE: A 74-year-old-female had a dermal analogue tumor in the parotid gland diagnosed by fine needle aspiration cytology (FNAC). Aspiration smears were characterized by aggregates of uniform epithelial cells, and cell groups bordered on thick, basement membrane-like material. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. CONCLUSION: Dermal analogue tumor of the salivary gland has a distinctive cytomorphologic appearance, and diagnosis of this neoplasm by FNAC is possible. Preoperative FNAC of salivary gland lesions is important in planning the most appropriate type of treatment.

Extramedullary plasmacytoma presenting as a primary mass in the breast. A case report.

BACKGROUND: Extramedullary plasmacytoma (EMP) of the breast is extremely rare, especially that not associated with multiple myeloma. CASE: A case of plasmacytoma of the breast in a 73-year-old man was diagnosed by fine needle aspiration cytology (FNAC). Aspiration smears revealed a dispersed population of plasmacytoid cells at various stages of maturation. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. CONCLUSION: FNAC diagnosis of plasmacytoma of the breast offers the opportunity to distinguish these neoplasms from primary mammary tumors and avoid unnecessary surgery.

[Sarcomatoid renal carcinoma. Report of 2 cases]. / Carcinoma renal sarcomatoide. Presentación de dos casos.

OBJECTIVE: To describe two cases of sarcomatoid renal carcinoma, one of them is alive after five years from surgery. METHODS: Both patients had undergone radical nephrectomy, without complementary treatment. RESULTS: One patient is alive after five years; the second patient presented acute renal failure and died after five days from surgery. CONCLUSIONS: Sarcomatoid renal carcinoma is a uncommon variety of renal cell carcinoma, with highly malignant behavior. The median survival is six months, but exceptional cases with larger survival (five years) have been reported in the literature.

Carcinoma renal sarcomatoide. Presentación de dos casos / Sarcomatoid renal carcinoma. Report of two cases

OBJETIVO: Presentar dos nuevos casos de carcinoma renal sarcomatoide, uno de los cuales tiene más de cinco años de supervivencia tras cirugía. MÉTODOS: Ambos pacientes fueron sometidos a nefrectomía radical, sin otro tipo de tratamiento coadyuvante. RESULTADOS: Uno de los pacientes presenta una supervivencia de más de cinco años; el segundo paciente falleció por fracaso renal agudo cinco días después de la intervención. CONCLUSIONES: Se trata de una neoplasia renal poco frecuente y altamente maligna. La supervivencia media es de seis meses, existiendo casos muy aislados en la literatura con supervivencias mayores de cinco años (AU)

Malignant phyllodes tumor with pleomorphic liposarcomatous stroma diagnosed by fine needle aspiration cytology: a case report.

BACKGROUND: Liposarcomatous differentiation within a phyllodes tumor is extremely rare. Cytologic and histologic findings of a case of malignant phyllodes tumor with liposarcomatous stroma of the breast are presented. CASE: A 45-year-old female had a malignant phyllodes tumor with pleomorphic liposarcomatous stroma diagnosed by fine needle aspiration (FNA) cytology. The cytologic findings were representative of the histologic features. CONCLUSION: Malignant phyllodes tumor of the breast can be diagnosed by FNA. It is very important to acknowledge the morphologic variants of sarcomatous stroma and to recognize the cytologic features of such rare tumors to prevent misdiagnosis as primary sarcomas of the breast. Preoperative diagnosis is important in planning the most appropriate type of treatment. It is also important to follow patients for long periods for recurrence and metastasis after surgery for this tumor.

Leiomioma vesical / Leiomyoma of the bladder

El leiomioma vesical es una neoformación benigna que supone menos del 0,43 por ciento de los tumores de vejiga. Se aporta un nuevo caso diagnosticado en un varón con síndrome prostático y litiasis vesical. Se realiza revisión de la literatura y se comentan los aspectos clínicos, diagnósticos y terapéuticos del mismo (AU)