BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.

BMC Clinical Pathology is an open access journal that publishes original peer-reviewed research articles covering all aspects of histopathology, hematology, clinical biochemistry, and medical microbiology, including virology, parasitology, and infection control. BMC Clinical Pathology (ISSN 1472-6890) is indexed, tracked, and covered by PubMed, CAS, EMBASE, Scopus, and Google Scholar.

《BMC Clinical Pathology》是一本开放获取的期刊，发表关于组织病理学、血液学、临床生物化学和医学微生物学（包括病毒学、寄生虫学和感染控制）各个方面的原创同行评审研究文章。《BMC Clinical Pathology》（ISSN 1472-6890）被PubMed、CAS、EMBASE、Scopus和Google Scholar等数据库索引、追踪和覆盖。

BMC Clinical Pathology

Abstract Background Whole-protein extracts from peripheral blood leukocytes are ideal for basic and clinical research. However, lack of a simple preparation technique has limited the use of such extracts. The aim of this study is to develop a simple and easy system that can selectively obtain leukocyte extracts without hemoglobin. Methods A filter that captures the leukocytes but not RBCs was set at the bottom of a 10-mL medical syringe by sandwiching it between plastic stoppers. The capturing efficiency of leukocytes with this tool, called LeukoCatch, was examined using human macrophage cells (MONO-MAC-6). The abilities of LeukoCatch system to capture the leukocyte proteins and to remove the hemoglobin from RBCs were tested by western blot analysis using human blood samples. Results This study presents the development of LeukoCatch, a novel tool that allows the preparation of leukocyte extracts from blood samples within 3 min without centrifugation. Tissue-cultured human macrophage cells were tested to determine the optimal filter numbers and pass-through frequencies of LeukoCatch, which was then applied to 2-mL blood samples. Samples were passed 2~5 times through a LeukoCatch equipped with 5 filters, washed twice with phosphate-buffered saline for red cell removal, and leukocyte proteins were extracted with 0.5 mL of elution buffer. Western blot analysis of the purified extract indicated that more than 90% of hemoglobin was removed by the LeukoCatch and that the protein recovery rate of leukocytes was at least 4 times better than that of the conventional centrifugation method. Conclusion We conclude that LeukoCatch is useful not only for diagnosis at the bedside but also for basic research using blood samples or tissue culture cells.

Daisuke Okuzaki

Shoichi Kimura

Norikazu Yabuta

Toshinari Ohmine

Hiroshi Nojima

LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts from blood

LeukoCatch：一种快速高效的从血液中制备白细胞提取物的工具

The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA. A determined oncogene other than PML-RARA which promotes cell proliferation would be required. We recently treated a 30-year-old Japanese female who achieved molecular remission with only the administration of all-trans retinoic acid. The patient’s leukemic clones concomitantly had a del(5q) aberrant chromosome with t(15;17) (q22;q12). The patient’s bone marrow cells indicated clonal evolution of the tumor cells expressing CD13dim, CD33+, CD117+, and lacking HLA-DR, CD34 and CD11b. A fluorescence in situ hybridization analysis detected PML-RARA fusion genes in the patient’s bone marrow specimens, leading to the diagnosis of acute promyelocytic leukemia. A del(5q) is one of the characteristic chromosomal abnormalities observed in myelodysplastic syndrome. On the other hand, up to 40 % of acute promyelocytic leukemia cases are known to harbor the addition of a clonal cytogenetic abnormality. However, such a case acute promyelocytic leukemia with del(5q) would be rare, rather than myelodysplastic syndrome, consequently obtaining t(15;17). Which cytogenetic abnormalities, acute promyelocytic leukemia or myelodysplastic syndrome, came first is informative to make a clinical decision for the initial therapy. In this case, we speculated the PML-RARA translocation is an original pathogenesis and thereafter additional cytogenetic abnormalities (del(5q) and -6) common in myelodysplastic syndrome. All-trans retinoic acid lead the patient into molecular remission. We propose that an assessment of additional cytogenetic abnormality in acute promyelocytic leukemia would contribute to the clinical decisions regarding whether to treat disease with all-trans retinoic acid and cytotoxic agents. It would be of interest to know the extent of cytogenetic abnormality in the patients regarding to mixed leukemia. One or more additional cytogenetic abnormalities other than PML-RARA could account for the biological malignant grade and prognostic index.

Osamu Imataki

Makiko Uemura

Chromosomal abnormality of acute promyelocytic leukemia other than PML-RARA: a case report of acute promyelocytic leukemia with del(5q)

急性早幼粒细胞白血病除PML-RARA外的染色体异常：一例伴del(5q)的急性早幼粒细胞白血病病例报告

Advanced genomic techniques such as Next-Generation-Sequencing (NGS) and gene expression profiling, including NanoString, are vital for the development of personalised medicines, as they enable molecular disease classification. This has become increasingly important in the treatment of cancer, aiding patient selection. However, it requires efficient nucleic acid extraction often from formalin-fixed paraffin-embedded tissue (FFPE). Here we provide a comparison of several commercially available manual and automated methods for DNA and/or RNA extraction from FFPE cancer cell line samples from Qiagen, life Technologies and Promega. Differing extraction geometric mean yields were evaluated across each of the kits tested, assessing dual DNA/RNA extraction vs. specialised single extraction, manual silica column based extraction techniques vs. automated magnetic bead based methods along with a comparison of subsequent nucleic acid purity methods, providing a full evaluation of nucleic acids isolated. Out of the four RNA extraction kits evaluated the RNeasy FFPE kit, from Qiagen, gave superior geometric mean yields, whilst the Maxwell 16 automated method, from Promega, yielded the highest quality RNA by quantitative real time RT-PCR. Of the DNA extraction kits evaluated the PicoPure DNA kit, from Life Technologies, isolated 2–14× more DNA. A miniaturised qPCR assay was developed for DNA quantification and quality assessment. Careful consideration of an extraction kit is necessary dependent on quality or quantity of material required. Here we provide a flow diagram on the factors to consider when choosing an extraction kit as well as how to accurately quantify and QC the extracted material.

Caroline Seiler

Alan Sharpe

J. Carl Barrett

Elizabeth A. Harrington

Emma V. Jones

Gayle B. Marshall

Nucleic acid extraction from formalin-fixed paraffin-embedded cancer cell line samples: a trade off between quantity and quality?

福尔马林固定石蜡包埋的癌细胞系样本核酸提取：数量与质量的权衡？

Mycetoma is a chronic granulomatous infectious disease caused by filamentous bacteria or by fungi. The disease is endemic in certain tropical and subtropical areas of the world but can be found elsewhere posing sometimes a diagnostic challenge for clinicians. A 65-year- old man presented with a right foot swelling evolving for 25 years. During that time, several diagnosis and treatments have been made without any improvement. The disease spread to bones, and misdiagnosed as Kaposi’s sarcoma. Transtibial amputation has been performed, and the histopathological examination revealed finally the diagnosis of eumycotic mycetoma. The patient recovered well after surgery and orthopedic prosthesis was prescribed for him. Mycetoma in non endemic areas is usually misdiagnosed and mismanaged leading to unnecessary and inappropriate surgery. Health practitioners should be aware of that fact in order to provide an accurate management.

Boubacar Efared

Layla Tahiri

Marou Soumana Boubacar

Gabrielle Atsam-Ebang

Nawal Hammas

El Fatemi Hinde

Laila Chbani

Mycetoma in a non-endemic area: a diagnostic challenge

非流行地区足菌肿：诊断挑战

Detection of vascular invasion by hematoxylin and eosin staining is the current pathological assessment practice to diagnose breast carcinoma. However, conventional hematoxylin and eosin staining failed to distinguish between blood vessel invasion and lymphatic vessel invasion. Both are important prognostic criteria however with different outcomes. The aim of this study is to distinguish between blood vessel invasion and lymphatic vessel invasion using conventional assessment and immunohistochemical markers. The prognostic significance of both circulatory invasions in invasive breast carcinoma was also investigated. Consecutive sections of breast carcinoma samples from 58 patients were stained with CD34 and D240 to stain blood and lymphatic vessels respectively. Hematoxylin and eosin staining was carried out on another consecutive section as conventional staining. Although blood vessel density is higher in the sections (median = 10.3 vessels) compared to lymphatic vessel density (median = 0.13), vessel invasion is predominantly lymphatic invasion (69.8 and 55.2% respectively). Interestingly, peritumoral lymphatic vessel density and peritumoral lymphatic invasion was significantly associated with distant metastasis (p = 0.049 and p = 0.05 respectively). The rate of false positive and false negative interpretation by hematoxylin and eosin was 46.7 and 53.3% respectively. Lymphatic vessel invasion is a strong prognostic markers of breast carcinoma invasion and the use of immunohistochemical markers increase the rate and accuracy of detection.

Nur Fatiha Norhisham

Choi Yen Chong

Sabreena Safuan

Peritumoral lymphatic vessel density and invasion detected with immunohistochemical marker D240 is strongly associated with distant metastasis in breast carcinoma

肿瘤周围淋巴管密度及D240免疫组化标记检测到的浸润与乳腺癌远处转移密切相关

Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype. However, an accurate understanding of melanoma in this part of the world is hindered by the very limited nature of prior publications. The aim of this study was to determine the epidemiological profile, anatomical distribution and histopathological features of melanoma presenting in Africans at a tertiary referral hospital in Malawi. This is a retrospective study that characterized melanoma cases diagnosed from January 2012 to December 2017, at a cancer referral centre in Malawi. All confirmed, malignant melanoma cases during the study period were retrieved. Data abstracted included age, sex, anatomic site and whether it was a primary or metastatic site. Breslow thickness in millimetres, Clark level of invasion, presence of ulceration and melanoma subtype were also evaluated. One hundred thirty-two cases were included in the study, 81 (61%) were female and 26 (20%) were from a metastatic site. The mean age was 57 years (sd = 15) with the majority in the age group 60–69 years. Males presented at an older age than females. Ninety five percent of cutaneous melanomas were located on acral sites, most commonly the foot (87%) and the most common histopathological subtype was acral lentiginous. Eighty four percent presented with a Breslow thickness over 4 mm (median 9 mm). Our study shows that malignant melanoma occurs in black people in Malawi and may be an under-appreciated malignancy. While long term clinical follow-up was not available, most patients presented at late stages of the disease, supporting a poor prognosis. These results suggest that increased awareness of melanoma in black Africans and earlier intervention may have meaningful impacts on outcomes and survival.

Maurice Mulenga

Nathan D. Montgomery

Maganizo Chagomerana

Tenganawo Mzumala

Tamiwe Tomoka

Coxcilly Kampani

Yuri Fedoriw

Satish Gopal

Lisbet Sviland

Epidemiological and histopathological profile of malignant melanoma in Malawi

马拉维恶性黑色素瘤的流行病学和组织病理学特征

Serum cystatin C (SCysC) and serum creatinine (SCr) are two biomarkers used in common practice to estimate the glomerular filtration rate (GFR). For SCysC and SCr to be used in a given population, normal values need to be determined to better assess patients. This study aimed to determine SCysC and SCr reference intervals (RIs) in a Cameroonian adult population and factors susceptible of influencing them.We carried-out a cross-sectional study from November 2016 to May 2017 in Yaoundé, Cameroon. Participants were Cameroonians aged 18 years and above, residing inside the country and found in good health at study inclusion. SCysC and SCr were determined by particle-enhanced turbidimetric immunoassay standardized against the ERM-DA471/IFCC reference material and by the IDMS reference modified Jaffe kinetic method, respectively. RIs were determined using the 2.5th and 97.5th percentiles and their respective 90% confidence intervals (CIs). The quantile regression served to identify potential factors likely influencing SCysC and SCr values.We included 381 subjects comprising 49.1% females.. RIs for SCysC varied between 0.57 (90%CI: 0.50-0.60) and 1.03 mg/L (90%CI: 1.00-1.10) for females, and from 0.70 (90%CI: 0.60-0.70) to 1.10 mg/L (90%CI: 1.10-1.20) for males. Concerning SCr, its RIs ranged from 0.58 (90%CI: 0.54-0.61) to 1.08 mg/dL (90%CI: 1.02-1.21) for females, and from 0.74 (90%CI: 0.70-0.80) to 1.36 mg/dL (90%CI: 1.30-1.45) for males. Men had significantly higher SCysC and SCr values than women (p < 0.001). Likewise, subjects aged 50 years and above had higher SCysC values in comparison to younger age groups (p < 0.001), which was not the case for SCr values (p = 0.491). Moreover, there was a positive and significant correlation between SCysC and SCr in women (ρ = 0.55, p < 0.001), in men (ρ = 0.39, p < 0.001) and globally (ρ = 0.58; p < 0.001). Furthermore, the sex influenced both biomarkers' values across all quantile regression models while age and body surface area (BSA) influenced them inconsistently.This study has determined serum cystatin C and serum creatinine reference intervals in an adult Cameroonian population, whose interpretations might take into account the patient's sex and to a certain extent, his/her age and/or BSA.

Bertille Elodie Edinga-Melenge

Adrienne Tchapmi Yakam

Jobert Richie Nansseu

Catherine Bilong

Suzanne Belinga

Eric Minkala

Prisca Armel Noudjeu

Michel Ondhoua

Samuel Walter Kokola

Vicky Joceline Ama Moor

Gloria Ashuntantang

Reference intervals for serum cystatin C and serum creatinine in an adult sub-Saharan African population

撒哈拉以南非洲成年人群血清胱抑素C和血清肌酐的参考区间

EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.

Ji-Lin Li

Shu-Han Lin

Hong-Qiu Chen

Li-Sheng Liang

Xian-Wei Mo

Hao Lai

Jie Zhang

Jing Xu

Bing-Qian Gao

Yan Feng

Yuan Lin

Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis

HER2和EGFR表达在伴有卵巢转移的结直肠癌患者中的临床意义

Vilazodone is an FDA approved medication used to treat major depressive disorder. The authors describe two cases of accidental vilazodone exposure in toddlers who presented with symptoms similar to amphetamine exposure and also with unexplained positive amphetamine urine immunoassay drug screens. Given a lack of published data on cross-reactivity of vilazodone and its metabolites with drug of abuse screening tests, the authors investigated drug of abuse immunoassay cross-reactivity of vilazodone and metabolites using computational and empirical approaches. To ascertain the likelihood that vilazodone would cross-react with drug of abuse screening immunoassays, the authors assessed the two-dimensional (2D) similarity of the vilazodone parent molecule and known metabolites to an array of antigenic targets for urine immunoassay drug screens. To facilitate studies of the commercially unavailable M17 metabolite, it was prepared synthetically through a novel scheme. Urine and serum were spiked with vilazodone and M17 into urine (200–100,000 ng/mL) and serum (20–2000 ng/mL) samples and tested for cross-reactivity. Computational analysis using 2D similarity showed that vilazodone and metabolites have generally low similarity to antigenic targets of common drug of abuse screening immunoassays, predicting weak or no cross-reactivity. The M17 metabolite had 2D similarity to amphetamines and tricyclic antidepressants in a range similar to some other compounds exhibiting weak cross-reactivity on these immunoassays. Cross-reactivity testing was therefore performed on two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. However, actual testing of cross reactivity for vilazodone and the M17 metabolite did not detect cross-reactivity for any urine amphetamines screen at concentrations up to 100,000 ng/mL and for a serum tricyclic antidepressants assays at concentrations up to 2000 ng/mL. While the vilazodone metabolite M17 has weak 2D structural similarity to amphetamines and tricyclic antidepressants, the current study did not demonstrate any experimental cross-reactivity with two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. Vilazodone ingestions in young children present a diagnostic challenge in their similarity to amphetamine ingestions and the lack of routine laboratory tests for vilazodone. Further work is needed to understand the metabolic profile for vilazodone in children versus adults.

Christina D. Martinez-Brokaw

Joshua B. Radke

Joshua G. Pierce

Alexandra Ehlers

Sean Ekins

Kelly E. Wood

Jon Maakestad

Jacqueline A. Rymer

Kenichi Tamama

Matthew D. Krasowski

Accidental intoxications in toddlers: lack of cross-reactivity of vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays

幼儿意外中毒：维拉佐酮及其尿液代谢物M17与药物滥用筛查免疫测定无交叉反应性

The overexpression of HER2 is associated with worse prognosis of breast cancer which responds favourably to anti-HER2 therapy. The objective of this study was to determine the frequency of HER2 and its association with clinicopathologic factors in breast cancer in Ivory Coast.The study included 608 patients who were histologically diagnosed with invasive primary breast carcinoma. The immunohistochemistry testing for ER, PR, and HER2 was performed on the formalin fixed paraffin-embedded blocks of breast tissue of these patients. The analysis of variance and the Chi-Square Test were used to examine the association of the HER2 status with clinicopathologic prognostic features.The average age of patients was 47 ± 11 years. Among 608 patients, 355 (58.4%) were premenopausal. Invasive ductal carcinoma of no specific type (511 cases, 84.1%) was the most frequent histologic type. Grade II tumors were 59.8%. The positivity of ER, PR, and ER/PR was 334 cases (54.9%), 252 cases (41.4%), and 356 cases (58.5%), respectively. HER2 was overexpressed in 105 cases (17.3%). The overexpression of HER2 was significantly correlated with Nottingham grade (p = 0.007). No association was observed between HER2 expression and age (p = 0.568), menopausal status (p = 0.929), histologic type (p = 0.666), ER (p = 0.137), PR (p = 0.396), and ER/PR (p = 0.134).Breast cancer occurs in young women. HER2 status is closely related to Nottingham grade. The immunohistochemical analysis of HER2 has prognostic and therapeutic implications, and thus, contributing to efficient clinical management of patients.

Nguiessan Alphonse Aman

Brahima Doukoure

Kouadio Donatien Koffi

Baumaney Sylvanus Koui

Zie Cheick Traore

Mohamed Kouyate

Ahoua Benjamin Effi

HER2 overexpression and correlation with other significant clinicopathologic parameters in Ivorian breast cancer women

HER2 过表达及其与科特迪瓦乳腺癌女性其他重要临床病理参数的相关性

Publication Information	Publisher: BioMed Central Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2001，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%

BMC Clinical Pathology

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