Fibroadenoma masquerading carcinoma on fine-needle aspiration of the breast.

OBJECTIVE: Benign and malignant lesions of the breast may have similar appearances on fine-needle aspiration cytology. We report a case of fibroadenoma that was diagnosed as carcinoma by cytology. CASE STUDY: Breast fine-needle aspiration biopsy was highly cellular and composed of bland-appearing spindle/columnar cells that could represent either epithelial or stromal cells; the case was reported as positive and the patient had subsequent excisional biopsy taken. RESULTS: On microscopic examination, smears were hypercellular and had many single cells and clusters of columnar/ elongate cells No obvious bipolar cells of myoepithelial origin were seen. Significant atypia was noted. Immunocytochemistry for smooth muscle actin was not performed due to insufficient material. CONCLUSIONS: Some cases of fibroadenoma and carcinoma can be very difficult to distinguish on fine needle aspiration cytology smears. Immunocytochemistry may be of help if sufficient material is provided. To avoid false positive diagnosis on cytology, it is best to report such a case as intermediate (atypical/suspicious) with final interpretation pending excisional biopsy.

Primary MALT lymphomas of the stomach: a pathological study of 18 cases.

AIM: It is doubtful that whoever is suffering from gastric malt lymphoma will escape from the disease, if treated with medication against helicobacter pylori. MATERIAL AND METHODS: A cohort of 18 patients was analysed. Ten hosts had primary gastric malt lymphoma and were treated with gastric resection as the initial therapy. Eight hosts received antibiotics against Helicobacter pylori as the initial treatment. In all 18 patients Helicobacter pylori status, endoscopic findings and pathology features were evaluated. Immunohistochemistry was performed to assess the bcl-2 and p53 status. RESULTS: Patients with low grade malt lymphoma: a) were Helicobacter pylori positive (5 of 5); b) had a superficial lesion (5 of 5); c) had no lymph node involvement (5 of 5); and d) were downstaged by comparison to patients with high grade tumor. Bcl-2 was positive in 4 of 5 low grade tumors, and p53 was positive in 12 of 13 high grade ones. Investigation of patients with 5-year follow up (n = 18) revealed that all but one low-grade tumors remained superficial with no progression. These tumors were bcl-2+/p53-, and the one with a bcl-2+/p53+ immunophenotype progressed to an ulcerated low-grade tumor after disappearance of Helicobacter pylori. Complete regression was found in 6 of 8 patients from the non surgically treated group (n = 8) after Helicobacter pylori eradication. These tumors were superficial/low grade/node negative/bcl-2+/p53 inconclusive (n = 2), superficial/low grade/node negative/bcl-2+/p53- (n = 2), and ulcerative/high grade/node negative/bcl-2+/p53- (n = 2). The two persistent tumors were ulcerative/high grade/node negative/bcl-2+/p53+. CONCLUSION: Gastric malt lymphoma Helicobacter pylori+/superficial/low grade/bcl-2+/p53- will disappear after Helicobacter pylori eradication.

Primary MALT lymphomas of the stomach: a pathological study of 18 cases

Objetivo: es difícil que alguien que padezca un linfoma gástrico de tipo MALT pueda librarse de la enfermedad,... a menos que se le trate con medicación para Helicobacter pylori. Material y métodos: se analizó una cohorte de 18 pacientes. Diez huéspedes tenían linfoma gástrico de tipo MALT y se trataron con resección gástrica como tratamiento inicial. Ocho recibieron antibióticos frente a Helicobacter pylori como tratamiento inicial. En los 18 pacientes se evaluaron la presencia de Helicobacter pylori, los hallazgos endoscópicos y los rasgos patológicos. Se realizó una inmunohistoquímica para valorar el bcl-2 y el p53. Resultados: los pacientes con linfoma MALT de grado bajo: a) dieron positivo a Helicobacter pylori (5 de 5); b) tenían una lesión superficial (5 de 5); c) no tenían afectados los ganglios linfáticos (5 de 5); y d) se estadificaron a la baja por comparación con los pacientes con tumores de grado alto. El bcl-2 fue positivo en 4 de los 5 tumores de grado bajo y el p53 fue positivo en 12 de 13 de los de grado alto. El estudio de los pacientes durante un seguimiento de 5 años (n = 18) reveló que todos los tumores menos uno de grado bajo siguieron siendo superficiales sin progresión. Estos tumores eran bcl-2+/p53-, mientras que el único con inmunofenotipo bcl-2+/p53+ progresó hasta convertirse en un tumor de bajo grado ulcerado tras la desaparición de Helicobacter pylori. Se observó una regresión completa en 6 de los 8 pacientes del grupo no tratado con cirugía (n = 8) tras la erradicación de Helicobacter pylori. Estos tumores eran superficiales, de bajo grado, con ganglios negativos y bcl-2+/p53 no concluyente (n = 2); superficiales, de bajo grado, con ganglios negativos y bcl-2+/p53- (n = 2), y ulcerativos, de grado alto, con ganglios negativos y bcl- 2+/p53- (n = 2). Los dos tumores persistentes eran ulcerativos, de grado alto con ganglios negativos y bcl-2+/p53+. Conclusión: el linfoma gástrico de tipo MALT, Helicobacter pylori-positivo, superficial, de grado bajo y bcl-2+/p53- desaparece tras la erradicación de Helicobacter pylori

Aim: it is doubtful that whoever is suffering from gastric MALT lymphoma will escape from the disease, if treated with medication against helicobacter pylori. Material and methods: a cohort of 18 patients was analysed. Ten hosts had primary gastric malt lymphoma and were treated with gastric resection as the initial therapy. Eight hosts received antibiotics against Helicobacter pylori as the initial treatment. In all 18 patients Helicobacter pylori status, endoscopic findings and pathology features were evaluated. Immunohistochemistry was performed to assess the bcl-2 and p53 status. Results: patients with low grade MALT lymphoma: a) were Helicobacter pylori positive (5 of 5); b) had a superficial lesion (5 of 5); c) had no lymph node involvement (5 of 5); and d) were downstaged by comparison to patients with high grade tumor. Bcl-2 was positive in 4 of 5 low grade tumors, and p53 was positive in 12 of 13 high grade ones. Investigation of patients with 5-year follow up (n = 18) revealed that all but one low-grade tumors remained superficial with no progression. These tumors were bcl-2+/p53-, and the one with a bcl-2+/p53+ immunophenotype progressed to an ulcerated lowgrade tumor after disappearance of Helicobacter pylori. Complete regression was found in 6 of 8 patients from the non surgically treated group (n = 8) after Helicobacter pylori eradication. These tumors were superficial/low grade/node negative/bcl-2+/p53 inconclusive (n = 2), superficial/low grade/node negative/bcl- 2+/p53- (n = 2), and ulcerative/high grade/node negative/bcl- 2+/p53- (n = 2). The two persistent tumors were ulcerative/high grade/node negative/bcl-2+/p53+. Conclusion: gastric MALT lymphoma Helicobacter pylori+/ superficial/low grade/bcl-2+/p53- will disappear after Helicobacter pylori eradication

Loss of chromosome 1 in myxopapillary ependymoma suggests a region out of chromosome 22 as critical for tumour biology: a FISH analysis of four cases on touch imprint smears.

OBJECTIVE: Ependymomas are glial tumours. They constitute approximately 5-10% of intracranial tumours and are tumours which can recur. Predictive factors of outcome in ependymomas are not well established. Karyotypic studies are relatively scarce and loss of chromosome 22 has been described to correlate with recurrence. We are unaware of any reports involving chromosome 1 aberrations in the malignant progression of ependymomas. METHODS: Cytogenetic analysis of four myxopapillary ependymomas was performed using double target fluorescent in situ hybridization (FISH), focusing on chromosomes 1 and 22. RESULTS: One patient's tumour had recurred. FISH was performed on 500 nuclei/tumours. All four cases showed a loss of chromosome 22q while only one showed an additional loss of chromosome 1p, and this was the one that recurred. CONCLUSIONS: We support the presence of a tumour suppressor gene on 1p associated with relapse in myxopapillary ependymomas and suggest that status of chromosome 1p by FISH may indicate a high-risk group of patients harbouring this tumour. More studies of this type are needed towards this direction as our results refer to a minimal number of individuals analysed.

NCL-CD30 staining of epithelial cells in the basal germinative layer of the epidermis and epithelial buds during foetal skin development.

The fact that the CD30 molecule can mediate signals for cell proliferation or apoptosis prompted us to perform a systematic investigation of CD30 antigen expression in embryonal tissues during proliferation and differentiation stages. We first targeted the foetal human intestinal cryptae cells with positive results. The epidermis is a dynamic epithelium that is constantly renewed throughout life. The basal layer, attached to the basement membrane, contains the dividing cells of the skin and as cells move up from this layer they undergo differentiation, ending in the formation of a terminally differentiated anucleate cell called squame. It is intriguing to find out if cells in the basal layer can express the CD30 antigen. We investigated the immunohistochemical expression of CD30 antigen in 15 paraffin-embedded tissue samples representing epidermis and epidermal buds from foetuses after spontaneous abortion in the 8th, 10th and 12th weeks of gestation, respectively, using the monoclonal antibody NCL-CD30. A Northern blotting analysis was additionally performed. The results showed that: (1) the epithelial cells of the epidermis in the developing skin express the CD30 antigen; (2) CD30 expression in these epithelial cells is higher in cases of hormonal administration than in normal gestation; (3) a similar positive reaction involved the epidermal buds associated with the development of the skin appendages. Northern blots of tissue sections using a CD30 cDNA probe detected mRNAs of the same molecular mass and variety similarly to those in the positive control cell line HUT 102.

Ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and synchronous cervical squamous carcinoma.

Solid mural nodule within a mucinous cystic ovarian tumor occurs more often than generally presumed. One especially interesting case involving coincidental cervical carcinoma is presented. A 38-year-old woman underwent exploratory laparotomy for a right ovarian tumor. After ovarian malignancy had been diagnosed from frozen section, the bilateral salpingo-oophorectomy and hysterectomy was performed. The tumor had a unilocular cystic cavity and a mural nodule. The nodule showed undifferentiated carcinomatous features. The immunohistochemical examination revealed atypical cells in the nodule which were positive for cytokeratin, CEA, and vimentine, establishing its anaplastic nature. A synchronous cervical invasive squamous carcinoma was documented. The patient was treated with chemotherapy and radiotherapy. Currently, at 15 postoperative months, she is well and free of disease. The occurrence of ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and cervical squamous cell carcinoma is evidently very uncommon, because we have not found a similar case in the literature.

Post transplantation human herpes virus-8 unrelated primary effusion lymphoma of the peritoneal cavity in a HIV-negative female

El linfoma de derrame primario (PEL) es una forma individualizada recientemente de linfoma no hodgkiniano(clasificación de la OMS), que se desarrolla principalmente en varones infectados con HIV, más frecuentementehomosexuales, en estadios avanzados de la enfermedad (recuento total de linfocitos CD+ 100-200/µl).Ocasionalmente aparece en otros estados de inmunosupresión (como durante el período de trasplante de órganossólidos) e incluso, aunque muy rara vez, en pacientes inmunocompetentes. Desde un punto de vista patogénico,el PEL se ha relacionado con el herpesvirus asociado al sarcoma de Kaposi (también llamado herpesvirus8 humano y HHV 8) y antecedentes clínicos de sarcoma de Kaposi. La frecuencia relativamente baja de la enfermedad,la ausencia de una casuística que permita una mejor caracterización y su desenlace desfavorable,apoyan la necesidad de profundizar en su conocimiento. Presentamos aquí los hallazgos clínico-biológicos deun paciente negativo para HIV, que fue diagnosticado de PEL peritoneal, originado en células T y no asociadoa HHV 8, cinco años después de un trasplante renal

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin lymphoma (WHOclassification), developing mainly in HIV-infected males, more frequently homosexual, in advanced stages ofthe disease (total CD4+ lymphocyte count below 100-200/µl). Occasionally, it appears in otherimmunosupressive states (such as solid organs transplantation period) and even, although very rarely, inimmunocompetent patients. From a pathogenic point of view, PEL has been related to Kaposi's sarcomaassociated herpes virus (also named human herpesvirus 8, HHV 8) and to clinical antecedents of Kaposi'ssarcoma. The relatively low frequency of this disease, the absence of a wide casuisticsts allowing a bettercharacterization, and its unfavourable outcome, support the need of a deeper knowledge. We present here theclinico-biological findings of a HIV-negative patient, who was diagnosed of peritoneal PEL, of T cell origin,and not HHV 8-associated, five years after renal transplantation

Unremitting early stage Hodgkin disease: report of 7 cases and bone marrow tissue immunohistochemical marker study

Es infrecuente la implicación de la médula ósea en la enfermedad de Hodgkin temprana. Estudiamos la composicióninmunohistoquímica del tejido de la médula ósea en 7 de 20 casos de enfermedad de Hodgkin temprana,de la variante de celularidad mixta, diagnosticada en la presentación inicial por biopsia de los ganglios linfáticos,que no respondieron a la radioterapia sola, con objeto de examinar la posible afectación de la médulaósea. Se encontró una frecuencia estadísticamente significativa de infiltrados positivos para CD45, CD45RO yCD4 asociados a la falta de remisión de la enfermedad. El predominio de células positivas para CD4 en lacomposición de la médula ósea: 1) podrían corresponder a su compromiso en el proceso, 2) podrían explicar laproducción anormal de citoquinas que llevan a una reducción de la capacidad inmunológica de las células T ya la ineficacia de las respuestas antitumorales, a pesar de que la gran mayoría de las células infiltrantes son célulasinmunológicamente reactivas

Bone marrow is infrequently implicated in early stage Hodgkin’s disease. We studied theimmunohistochemical bone marrow tissue of 7 out of 20 cases with early stage Hodgkin’s disease of the mixedcellularity variant, diagnosed by lymph node biopsy at initial presentation, not responding to radiotherapyalone, in order to examine possible marrow attack. A statistically significant prevalence of CD45, CD45RO,and CD4 positive infiltrates, to the advantage of unremitting hosts, was found. The predominance of CD4-positive cells in the bone marrow space: 1) might be suggestive of involvement in the process, 2) could explainthe abnormal cytokine production leading to reduced T-cell immunity and inefficient antitumor responsedespite the existence of a vast majority of reactive infiltrating immune cells

Primary gastric Hodgkin's lymphoma: a case report and review of the literature.

Primary gastric Hodgkin's lymphoma is a rarely encountered lesion. Most cases are observed in the course of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin's lymphomas, after the employment of immunohistochemistry. Some Hodgkin's lymphomas may masquerade non-Hodgkin's lymphomas, and vice versa. Therefore, an accurate diagnosis is important, as treatment and outcome differ significantly for these entities. We report a case of primary Hodgkin's lymphoma arising in the stomach of a 46-year-old male, and discuss the diagnostic approach as well as the differentials of Hodgkin's disease in this anatomic site.

Intrahepatic extramedullary hematopoietic tumor mimicking metastatic carcinoma from a colonic primary.

BACKGROUND: Extramedullary hematopoiesis (EMH) is associated with a number of diseases in which the normal function of the bone marrow is disturbed. While organs with hemopoietic capacity like the liver and spleen are most commonly involved, EMH has also occasionally been found in other organs like the adrenal gland, lymph nodes, breast, thymus, small bowel and central nervous system. However, presentation of a myeloproliferative disorder, such as EMH in these organs is a rare event. CASE REPORT: We report clinical and fine-needle aspiration (FNA) findings in a patient who presented with intrahepatic EMH which mimicked metastatic carcinoma from a colonic primary. RESULTS: Ultrasound-guided FNA of the intrahepatic mass revealed megakaryocytes and myelocytes thus establishing the diagnosis of EMH. CONCLUSIONS: EMH is an unusual condition that can mimic other solid masses of the liver. Because radiologic findings are not specific, EMH should be considered in the differential diagnosis, especially in patients with a myeloproliferative disorder. FNA and subsequent cytopathological interpretation of the aspirates enables avoidance of unnecessary potentially hazardous surgery.

Cytological diagnosis of malignant mixed müllerian tumor of the uterus in ascitic fluid.

The malignant mixed Mullerian tumour (MMMT) is a rare and aggressive neoplasm of the uterus, seen in postmenopausal women. In this case, an uncommon neoplasm was diagnosed cytologically in the ascitic fluid of a woman 58 years old and was confirmed histologically after hysterectomy and bilateral adnexectomy.

Atypical CT findings of cervical lymphadenopathy due to Hodgkin's disease. A case report.

We describe a case of Hodgkin's disease with cervical lymphadenopathy which may easily be confused with a granulomatous process both radiologically and pathologically.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2. P53 and the wild-type (wt) p53-induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 does not maintain its suppressive effect on bcl-2 expression as has been reported in vitro. Further studies at the DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and wafl genes in SCLC pathogenesis.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2, p53 and the wild-type (wt) p53- induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 doses not maintain its suppressive effect on bcl-2 expression as it has been reported in vitro. Further studies at DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and waf1 genes in SCLC pathogenesis.

Expression of p53, mdm2, p21/waf1 and bcl-2 proteins in thymomas.

We have investigated the immunohistochemical expression of p53, mdm2, p21/waf1 and bcl-2 proteins in 31 thymic epithelial tumours comprising five medullary thymomas (MDT), four mixed thymomas (MT), 12 cortical thymomas (CT), eight predominately cortical thymomas (PCT) and two well-differentiated thymic carcinomas (WDTC). We have found p53, mdm2, p21 and bcl-2 protein expression in 25/31, 8/31, 5/31 and 10/31 thymic epithelial tumours, respectively. Coexpression of p53 and mdm2 proteins was found in eight cases (three CT, four PCT and one WDTC). Five of them were also p21 positive and three p21 negative. Discordant p53+/mdm2-/p21- protein expression was found in 19 cases (three MDT, three MT, nine CT, three PCT and one WDTC). Mdm2 and p21 proteins were not expressed in the absence of p53 protein. Coexpression of bcl-2 and p53 proteins was found in seven cases (three MDT, three MT and one WDTC). Eighteen cases were p53+/bcl-2- (10 CT, seven PCT and one WDTC) and three cases (two MDT and one MT) were bcl-2+/p53-. Our findings indicate that in thymomas, p53 expression is more frequently associated with cortical histotypes while bcl-2 expression is strongly associated with medullary and mixed histotypes. In addition, there is an inverse correlation between p53 and bcl-2 protein expression in thymomas. Coexpression of p53/mdm2/p21 proteins may reflect thymomas with wild-type (wt), p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. However, in view of previous findings that p53 mutation is an early event in thymomas, the possibility of p53 gene mutation with p53-independent mdm2 and p21 expression should be considered in these cases. Discordant p53+/mdm2-/p21- protein expression may represent thymomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins.

MIB1 (Ki-67) expression in non-Hodgkin's lymphomas.

The MIB1 monoclonal antibody which is used as a marker of cell proliferation was studied by immunohistochemistry on formalin-fixed and paraffin embedded biopsy specimens of lymph nodes in 40 high- and 46 lowgrade cases of non-Hodgkin's lymphomas (NHL) classified according to the Kiel classification. All cases were found to display nuclear MIB1 staining. A statistically significant difference (P < 0.005) was found between high- and low grade NHLs and this indicates that the high- grade NHL display a higher proliferation rate than low grade. In addition, remarkable variations in MIB1 expression were found among individual cases of the same histological group. These data may suggest that MIB1 index can help in the individual approach of the proliferation rate of each tumour and this may be an important parameter in association with clinical and other laboratory parameters for predicting the biological behaviour of non-Hodgkin's lymphomas.