BMC Clinical Pathology最新文献

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Background: Listeria monocytogenes is a bacterium present in some food products. It is rarely the cause of Rhombencephalitis in immunocompetent patients.

Case presentation: We report a case of an immunocompetent patient, presenting with progressive perioral numbness and dizziness. Despite treatment with antiplatelet drugs, antiviral medication, antibiotics and corticosteroids for a wide differential diagnosis, the patient deteriorated tremendously. Eventually the patient died of Listeria rhombencephalitis, most likely due to the late diagnosis and concomitant late initiation of antibiotics combined with badly timed and inappropriate corticosteroid prescription.

Conclusion: Early adequate antibiotic treatment is essential in Listeria rhombencephalitis and corticosteroid therapy should be avoided when Listeriosis is suspected.

Background: The development of molecular techniques to estimate the risk of breast cancer recurrence has been a significant addition to the suite of tools available to pathologists and breast oncologists. It has previously been shown that immunohistochemistry can provide a surrogate measure of tumor recurrence risk, effectively providing a less expensive and more rapid estimate of risk without the need for send-out. However, concordance between gene expression-based and immunohistochemistry-based approaches has been modest, making it difficult to determine when one approach can serve as an adequate substitute for the other. We investigated whether immunohistochemistry-based methods can be augmented to provide a useful therapeutic indicator of risk.

Methods: We studied whether the Oncotype DX breast cancer recurrence score can be predicted from routinely acquired immunohistochemistry of breast tumor histology. We examined the effects of two modifications to conventional scoring measures based on ER, PR, Ki-67, and Her2 expression. First, we tested a mathematical transformation that produces a more diagnostic-relevant representation of the staining attributes of these markers. Second, we considered the expression of BCL-2, a complex involved in regulating apoptosis, as an additional prognostic marker.

Results: We found that the mathematical transformation improved concordance rates over the conventional scoring model. By establishing a measure of prediction certainty, we discovered that the difference in concordance between methods was even greater among the most certain cases in the sample, demonstrating the utility of an accompanying measure of prediction certainty. Including BCL-2 expression in the scoring model increased the number of breast cancer cases in the cohort that were considered high certainty, effectively expanding the applicability of this technique to a greater proportion of patients.

Conclusions: Our results demonstrate an improvement in concordance between immunohistochemistry-based and gene expression-based methods to predict breast cancer recurrence risk following two simple modifications to the conventional scoring model.

Background: Urinary schistosomiasis is a common parasitic disease in endemic countries.

Case presentation: We report the case of a patient who was on a working trip to Mauritania. This parasitosis, suspected in the presence of hematuria and the notion of stay in an endemic zone, was confirmed by the presence of Schistosoma heamatobium eggs during the histological examination of the bladder biopsy performed after cystoscopy, highlighting a bilharzial granuloma and of course, the diagnosis was confirmed by the presence of eggs during the direct examination of the freshly collected urine.

Conclusions: It should be pointed out that the diagnosis of schistosomiasis must be evoked with the association of hematuria and the particular inflammatory aspect of the vesical mucosa and, of course, the notion of stay in an endemic zone.

Background: Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. Recent studies suggest that circulating cell-free plasma DNA of tumour origin (tDNA) is a promising non-invasive biomarker that can be used to predict the prognosis and monitor the efficacy of systemic treatments in patients with certain types of cancer. We conducted a pilot study to analyse the potential role of tDNA as a biomarker in patients with advanced gastric cancer.

Methods: We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples (10 mL of total blood) from each patient every 3 months and performed concomitant CT until disease progression or death. Total cell-free circulating DNA (cfDNA) samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. The cfDNA was used to evaluate the ALU DNA sequences 247 and 115. The level of tDNA was calculated from the ratio of the expression of ALU DNA sequences and the concentration of total cell-free DNA. We utilized the RECIST criteria 1.1 to evaluate the tumour response.

Results: Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls (p = 0.00015), which allowed us to conclude that the cfDNA in the patients originated from the tumour. We did not find any significant correlation between the level of tDNA and OS or tumour response. However, after the first cycles of chemotherapy (at 3 months), we observed that patients with lower tDNA levels had significantly longer DFS compared with those with higher levels (Cox Regression p = 0.0228).

Conclusions: At 3 months after the beginning of chemotherapy, the tDNA levels are correlated with DFS in patients with advanced gastric cancer who receive systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.

Background: to evaluate the intraobserver and interobserver reproducibility of cervical cytopathology according to previous knowledge of whether patients received radiotherapy (RT) treatment or not.

Methods: The study analyzed a sample of 95 cervix cytological slides; 24 with cytological abnormalities (CA) and presence of RT; 21 without CA and presence of RT; 25 without CA and without previous RT; 25 with CA and without previous RT. Two cytopathology (CP) evaluations of the slides were carried out. For the first CP re-evaluation, the cytotechnologist was blinded for the information of previous RT. For the second CP re-evaluation, the cytotechnologist was informed about previous RT. The results were analyzed through inter and intraobserver agreement using the unweighted and weighted kappa.

Results: Post radiotherapy effects were identified in 44.4% of cases that undergone previous pelvic RT. The agreement for RT status was 66.32% (unweighted K = 0.31, 95%CI: 0.13; 0.49, moderate agreement). The intraobserver agreement, regarding the cytological diagnoses, regardless of radiotherapy status, was 80.32% (weighted K = 0.52, 95%CI: 0.34; 0.68). In no RT group, the intraobserver agreement was 70% (weighted K = 0.47, 95%CI: 0.27;0.65) and in patients that received RT, the intraobserver agreement was 84.09% (unweighted K = 0.37, 95%CI: 0.01;0.74). The interobserver agreement between cytopathology result (abnormal or normal) in the group with RT, considering normal and abnormal CP diagnosis was 14.0% and 12.5%, respectively. There was no association between the cytological alterations and the median time between the end of RT and the cytological diagnosis.

Conclusion: This study showed that RT has an important impact in CP diagnosis because the agreement, also in interobserver and intraobserver analysis, had high discrepancy in patients that received RT. Also, demonstrated that it is difficult to recognize the presence of RT in cytological slides when this information is not provided.