Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.

Thymidylate synthase polymorphism in Mexican patients with colon cancer treated with 5-fluorouracil.

PURPOSE: We analyzed the genotype and allele frequency of variable number tandem repeats (VNTR)-thymidylate synthase (TS) and its relationship with the disease evolution in colon cancer patients. METHODS: We selected 24 paraffin-embedded colon cancer tissue samples from Mexican patients who received a 5-fluorouracil (5-FU)-based chemotherapy regimen. Tumor tissue was digested with proteinase K and genomic DNA was isolated by the standard method with phenol-chloroform extraction. Polymerase chain reaction (PCR) was performed for TS genotyping of VNTR and the results were evaluated directly in a stained agarose gel. RESULTS: The allele frequency of 2 repeats (2R) was greater (0.66) than 3R (0.34) in metastatic colon cancer (x2=10.24; p=0.001)) however, no difference in allelic distribution between 2R (0.54) and 3R (0.46) in non metastatic patients was observed (x2=0.640; p=0.424). CONCLUSION: Our results suggest that Mexican patients with colon cancer present differences in the allelic distribution, the 2R allele being the most frequent.

CDX-2, MUC-2 and B-catenin as intestinal markers in pure mucinous carcinoma of the breast.

BACKGROUND: Pure mucinous adenocarcinoma of the breast is a rare entity characterized by the production of variable amounts of mucin comprising 1% to 6% of breast carcinomas. Some mucinous adenocarcinomas have shown expression of intestinal differentiation markers such as MUC-2. This study examines the expression of intestinal differentiation markers in this type of breast carcinoma. RESULTS: Twenty-two cases of pure mucinous adenocarcinoma of the breast were assessed. Immunochemistry was performed for beta-catenin, CDX-2 and MUC-2. All cases were positive for B-catenin. MUC-2 positivity was observed in all cases; 63. 6% were 3 plus positive. All cases were negative for CDX-2. CONCLUSIONS: These results suggest that mucinous breast carcinomas express some markers of intestinal differentiation, such as MUC-2 and beta-catenin; however, future studies with a larger series of cases and using molecular techniques that help affirm these results are needed.

Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features.

A 56-year-old woman debuted with a palpable painless mass in the anterior thorax wall at the level of the second and third right parasternal intercostal space, which progressively increased in size over 5 months accompanied by localized skin rash, mild dyspnea and chest pain when changing position. Imaging studies showed a soft tissue mass measuring 75 × 62 mm and a density of 34 Hounsfield Units that had caused the lysis of the costal arches and grew expansively towards the anterior mediastinum, without identifying mediastinal adenopathies only by this imaging method. Core biopsy was performed, which was initially diagnosed as histiocytic sarcoma (HS); however, when the diagnostic panel was expanded to include molecular and NGS studies, the final diagnosis was anaplastic large cell lymphoma with ALK::ATIC fusion. Here, we report a very rare neoplasm with unusual clinical presentation, histopathology and molecular features.

Navigating HER2-Low Testing in Invasive Breast Cancer: Update Recommendations for Pathologists.

The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology.

TSPAN33 is a novel marker of activated and malignant B cells.

We have identified Tspan33 as a gene encoding a transmembrane protein exhibiting a restricted expression pattern including expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in primary human B cells following activation. Human 2E2 cells, a Burkitt's lymphoma-derived B cell model of activation and differentiation, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in several lymphomas including Hodgkin's and Diffuse large B cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases where B cells participate in the pathology, including rheumatoid arthritis patients, systemic lupus erythematosus (SLE), and in spleen B cells from MRL/Fas(lpr/lpr) mice (a mouse model of SLE). We conclude that TSPAN33 may be used as a diagnostic biomarker or as a target for therapeutic antibodies for treatment of certain B cell lymphomas or autoimmune diseases.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Intestinal-type adenocarcinoma arising from a villous adenoma in the renal pelvis in the context of a kidney abscess: Case report.

Villous adenoma is a benign neoplasm with an exceptional presentation in the renal pelvis, hence very few cases have been reported. Herein we present the case of a patient who presented with left flank pain clinically suggestive of complicated pyelonephritis, culminating in simple nephrectomy with a villous adenoma in the renal pelvis as histopathological finding associated to the presence of a microscopic focus of intestinal-type adenocarcinoma.

[Large cell carcinoma of the lung with null immunophenotype: Case report & brief review]. / Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura.

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.

[The imprint cytology: a tool diagnosis in the operating room]. / Impronta citológica: herramienta en el diagnóstico transoperatorio.

BACKGROUND: since 1929, the imprint cytology has a great value in the transoperatory as a diagnostic tool and in some cases as an alternate method. METHODS: during two years period, 416 transoperatory specimens and 384 frozen sections were performed in the Pathology and Cytopathology Department of the University Hospital, "Dr. José E. Gonzalez." Diagnoses were recorded and compared both methods with the final diagnosis given at definitive histological sections. The results were evaluated and p statistics were performed. RESULTS: nine of 416 patients (2.2 %) were incorrectly diagnosed by cytology, and 8 of 384 (2.1 %) by frozen section. The diagnostic accuracy for the imprint cytology was 97.8 % and 97.9 % for frozen section. Six of the 416 cases (1.4 %) were misdiagnosed by imprints and frozen sections; the percentage success was 98.5 % using both methods together. The p was statistically significant (0.0005). CONCLUSIONS: the transoperatory cytology is a fast, easy and inexpensive. It provides morphological detail on intact cells and without the freezing artifacts, so its use as an adjunct to the frozen method is of great value.

Diagnosis of carcinosarcoma metastatic to the umbilicus by fine needle aspiration biopsy: a case report.

BACKGROUND: Metastasis to the umbilicus, known as Sister Mary Joseph's nodule, sometimes represents the first clinical manifestation of an internal malignancy. These nodules are infrequent, and their discovery has prognostic implications. CASE: An 86-year-old woman presented with an ultrasound diagnosis of peritoneal carcinomatosis and the presence of a round lesion in the umbilical area. A fine needle aspiration biopsy was performed. The cytologic smears showed a biphasic neoplasm composed of malignant epithelial cells with a glandular appearance and randomly scattered spindle cells in a necrotic base. Immunohistochemical staining was performed to confirm the diagnosis. CONCLUSION: After an extensive search of the literature, we discovered that this is the first report of a metastatic carcinosarcoma diagnosed by fine needle aspiration biopsy. The diagnosis of carcinosarcoma requires a clear definition of the 2 components, which is why immunohistochemical staining is very useful. The presence of an umbilical nodule should raise suspicion of an underlying malignant neoplasm. Needle aspiration biopsy should be considered as the most effective, simple, uncomplicated method of diagnosing these lesions.

[Ovarian ginandroblastoma as a transcesarean incidental finding. A case report and literature review]. / Ginandroblastoma de ovario como hallazgo transcesárea. Reporte de un caso y revisión de la bibliografía.

The gynandroblastoma is an extremely rare sexual cord stromal tumor, which contains both male and female elements, characterized by Sertoli or Leydig cells and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old female patient, found accidentally during a cesarean section operation. There is only one reported case in world literature occurring in a pregnant woman. The principal component we found was adult granulose cells, with a microfollicular pattern, and the presence of luteinized cells in some areas; besides we found the presence of well differentiated Sertoli cells elements, in addition to Leydig cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings were performed: citokeratin, which resulted positive in Sertoli cells and negative in granulose cells; and inhibin, which was positive in both components showing its mixed origin.

Selective efficacy and safety of first line and non front line antineoplasic agent combinations determined with individualized assays on colorectal cancer primary cultures.

PURPOSE: To evaluate the efficacy of first-line and not-conventional antineoplastic drug combinations in colorectal adenocarcinoma primary cultures (CRAC PCs). METHODS: The efficacy and safety of 21 drug combinations (DCs) were evaluated using a simplified adenosine triphosphate-based chemotherapy response assay (sATP-CRA). The efficacy of each DC was reported as the percentage of cell death (PCD) produced on each of 12 CRAC-PCs, and the safety of each DC was evaluated as a safety window (SW). The SW was calculated as the quotient of PCD-CRAC PC/PCD-hMSC-TA (human mesenchymal stem cells derived from adipose tissue). Nine DCs contained 5-fluorouracil and oxaliplatin, and 1-3 non-front line drugs (NFLDs [carboplatin, doxorubicin, cisplatin, aspirin, or 3,3' diindolylmethane]). The other 11 DCs only contained 2-4 NFLDs. RESULTS: The efficacy and safety each DC were highly variable and depended on each CRAC PC and DC. The usefulness of DCs was considered as a combination of PCD >20 and an SW >0.6: 13 /21 DCs (62%) met the requirements of efficacy and safety on 7/12 CRAC PCs (58.3%). CONCLUSIONS: The resistance to 5-fluorouracil/oxaliplatin of CRAC PCs and the usefulness of seven new DCs strongly suggest the convenience of performing ex vivo individualized assays to evaluate DCs, and implement new and more useful treatments, instead of submitting patients to standardized chemotherapies in a blinded manner. Approaches such as this and properly evaluated in clinical assays could increase the life expectancy of patients with cancer and improve their quality of life.

Diagnostic utility of invasive tests and serology for the diagnosis of Helicobacter pylori infection in different clinical presentations.

BACKGROUND: Invasive and noninvasive tests are used for the diagnosis of Helicobacter pylori infection. The aim of this study was to determine the diagnostic utility of rapid urease test (RUT), culture, histology and serology for the diagnosis of H. pylori in patients with different clinical presentations. METHODS: We studied 527 consecutive patients (mean age, 52.5 years; F:M, 1.3; age range 15-89 years) enrolled at the Hospital Universitario, Universidad Autónoma de Nuevo León. Patients had gastric cancer (GC, 9.1%), non-ulcer dyspepsia (NUD, 81.4%), or peptic ulcer disease (PUD, 9.1%). The infection by H. pylori was determined by histology, rapid urease test, culture, and serology. Patients were determined as infected with H. pylori if at least a) two invasive tests were positive and b) two tests were positive (invasive or non-invasive). Diagnostic utility was calculated for each assay. RESULTS: Prevalence of infection in the whole studied population was 50.9%. In NUD patients the prevalence was 51.3%, in PUD patients 58.3%, and in GC patients 39.6%. When we used the first diagnostic criteria, for the whole studied population, the RUT was the most reliable test, followed by the culture. Histology had the best sensitivity for the whole studied population and NUD patients and RUT had the best sensitivity value for the GC patients. In the whole studied population, NUD and GC patients, RUT and culture had the best specificity, accuracy and PPV. For PUD patients, serology had the best performance. When we used the second diagnostic criteria, histology and serology had a better performance compared with the results obtained with the first diagnostic criteria. CONCLUSIONS: Diagnostic utility of the tests varies according to the clinical presentations, which should be considered in the selection of the diagnostic test for the detection of H. pylori.

[Her2-Neu expression in ductal adenocarcinomas of the breast gland: correlation with histopathological parameters and estrogen receptors' expression in Mexican patients]. / Expresión del Her2-Neu en el adenocarcinoma ductal de la glándula mamaria: correlación con parámetros histopatológicos y expresión de receptores estrogénicos en pacientes mexicanas.

BACKGROUND: Breast cancer is a general health problem that annually produces 400,000 deaths worldwide. Its early diagnosis leads to high cure rates; nevertheless, in Mexico City this happens rarely. Her2-Neu is an oncogene that is expressed on breast cancer cells, with aggressive behaviour and metastasis. In the United States 20 to 30% of the patients present an over-expression of this protein. This phenomenon has been used as a prognostic parameter and as a predictive and indication factor for therapy with monoclonal antibodies directed against this protein and for therapy with taxanes. OBJECTIVE: To know the biology and distribution of Her2-Neu expression in Mexican breast cancer patients in order to evaluate its potential as a prognostic and predictive factor in the treatment of the breast cancer. PATIENTS AND METHOD: In the cases of invasive ductal adenocarcinomas of the breast we compared by immunohistochemistry the Her2-Neu and estrogen receptor expressions with the histopathological characteristics. The results were evaluated statistically. RESULTS: We found 122 cases of breast adenocarcinoma, from which we evaluated 108 for fulfilling the selection criteria of invasive ductal adenocarcinoma. Patient's mean age was 51.8 +/- 13.2 years. The mean tumour diameter was 3.5 +/- 2.0 cm and the mean number of lymph nodes with metastasis was 6.8. The Her2-Neu (score 2+ and 3+) expression was found in 36.1% of the patients. The tumour diameter and the presence of metastatic disease had strong relation with the Her2-Neu expression level. We did not find correlation with the differentiation level, the patient's age and the presence or absence of oestrogen receptors. CONCLUSIONS: Since the percentage of patients with Her2-Neu expression is high (36.1%) and there is a close relation between Her2-Neu expression, the tumour size and the presence of lymph node methastasis, the determination of the oncoprotein expression could allow a more detailed prognosis and the treatment with immunotherapy and anthracyclines in order to influence the course of the breast cancer cases.

Fine needle aspiration biopsy diagnosis of metastatic neoplasms of the breast. A three-case report.

Metastases to the breast are unusual lesions that make up approximately 2% of all malignant mammary neoplasms and may mimic both benign and malignant primary neoplasms from a clinical point of view, as well as in imaging studies. Arriving at a correct diagnosis is therefore essential in order to establish appropriate management. We present three cases of metastatic neoplasms diagnosed through fine needle aspiration biopsy and immunocytochemistry. The cytological diagnoses were: medulloblastoma in an 18-year-old woman, melanoma in a 26-year-old man, and an exceptional case of ovarian sarcoma originating from a granulosa cell tumor with metastases to both breasts. A metastatic disease should be considered in the differential diagnosis of a palpable mass in the breast, especially if there is a history of an extramammary malignant neoplasm. Fine needle aspiration biopsy is the method of choice for the management of these cases. Whenever possible the exam of the material obtained should be compared to the previous biopsy, which is usually enough to arrive at a correct diagnosis, thus preventing unnecessary surgical procedures.

Association of gastric cancer, HLA-DQA1, and infection with Helicobacter pylori CagA+ and VacA+ in a Mexican population.

BACKGROUND: The goal of this study was to determine the importance of Helicobacter pylori CagA+, VacA+, and HLA-DQA1 alleles in a Mexican population with gastric cancer (GC). METHODS: We studied a group of Mexican patients (cases) with distal GC (n=22) or high-grade dysplasia (HGD; n=8) (mean age, 62.7 years, F : M=0.3; age range, 33-84 years) and 77 ethnically matched non-GC controls (mean age, 47.1 years; F : M=1.96; age range, 17-92 years). Both cases and controls were H. pylori-positive by at least two of the following diagnostic tests: rapid urease test, histology, culture, or serology. The presence of antibodies to CagA and VacA proteins was determined by Western blot, and the HLA-DQA1 typing was carried out by a polymerase chain reaction (PCR) sequence-specific primer method. RESULTS: The carriage of H. pylori CagA+, VacA+ strains was associated with GC or HGD (odds ratio [OR], 6.07; 95% confidence interval [CI], 1.56-27.57; P=0.005). The allele frequency of DQA1*0503 was significantly lower in the GC-HGD group than in the non-GC group (OR, 0.13; 95% CI, 0.02-0.59). Logistic regression analysis identified the carriage of HLA-DQA1*0503 as an independent protective factor for GC (OR, 0.19; 95% CI, 0.04-0.94) and colonization with H. pylori CagA+, VacA+ strains as an independent risk factor for GC (OR, 6.15; 95% CI, 1.69-22.37). CONCLUSIONS: Infection with H. pylori CagA+, VacA+ strains represents a significant risk for the development of GC. The absence of HLA-DQA1*0503 could be a host risk factor for the development of GC in Mexican patients.