Merkel Cell Carcinosarcoma With a Bland Sarcomatous Component.

ABSTRACT: Merkel cell carcinoma with a sarcomatous component is very rare, with only 12 cases reported in the literature, often with overtly malignant myoid differentiation. We report a case of metastatic Merkel cell carcinosarcoma presenting in a lymph node 6 months after a diagnosis of cutaneous Merkel cell carcinoma with conventional histologic features. The metastatic lesion showed a unique biphasic appearance with admixed populations of neuroendocrine epithelial cells and fascicles of mitotically active spindle cells with mild cytological atypia. In addition to the immunomorphological features, a common molecular profile between the epithelial and mesenchymal components further supported the notion of carcinosarcoma in this case. To the best of our knowledge, a bland sarcomatous component has not been previously described in Merkel cell carcinosarcoma, which can be easily overlooked as a reactive stromal reaction microscopically.

Metastatic Melanoma to a Neurofibroma.

ABSTRACT: We present an extraordinary case of metastatic cutaneous melanoma to a pre-existing neurofibroma in a 75-year-old man with a history of primary invasive melanoma in an anatomically close vicinity. Histological examination of the metastatic melanoma showed a well-circumscribed intradermal nodule of frankly malignant epithelioid melanocytes without an intraepidermal component, surrounded and sharply demarcated from a diffuse spindle cell proliferation with morphological features of a neurofibroma. The spindle cell component showed bland cytologic features, with no mitotic activity or lymphocytic inflammation and no features of malignancy. By immunohistochemistry, both components expressed S100, while HMB45 positivity and complete loss of p16 were only observed in the epithelioid cells. The morphologically distinct areas were analyzed by fluorescent in situ hybridization, which demonstrated an abnormal profile (gain of RREB1 and homozygous loss of CDKN2A) in the epithelioid nodule; however, no abnormalities were detected in the spindle cell component. Next-generation sequencing showed somatic NRAS and PTEN mutations in the melanoma cells only. The overall molecular findings supported the immunomorphological diagnosis of metastatic melanoma within a neurofibroma over the potential differential diagnosis of melanoma with a neurofibroma-like spindle/desmoplastic component.

An Atypical Deep Penetrating Nevus With Mutations in Beta Catenin , BRAFV600E , and IDH1R132C in an 8-Year-Old Boy.

ABSTRACT: Deep penetrating nevus (DPN) is a pigmented melanocytic tumor which typically displays a wedge-shaped deep penetrating architecture. Some cases show a coexisting component resembling conventional melanocytic nevus. These morphological attributes are correlated with the acquisition of genomic alterations in the Wnt pathway on a background of underlying activating MAPK pathway mutations. Lesions with features of DPN, but displaying expansile architecture, sheet-like arrangement of cells, cytological atypia, and/or more than rare mitotic activity have been described as "atypical deep penetrating nevus" or "deep penetrating melanocytoma." The molecular correlates of these atypical morphological features are not well-established. In this case report, we describe a tumor in an 8-year-old boy with histological features of atypical DPN showing somatic BRAFV600E , beta catenin , and IDH1R132C mutations. The combination of abnormalities in MAPK and Wnt pathways with IDH1 mutations seems to be a reproducible feature in a subset of atypical DPNs. Whether this "three-hit" combination is associated with a significant risk of adverse outcome remains to be established.

Factors in Psychiatric Admissions: Before and During the Covid-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic has impacted community mental health, but the effect on psychiatric admissions is unknown. We investigated factors contributing to acute psychiatric admissions, and whether this changed during the first UK lockdown. METHOD: A retrospective case-note review study with an exploratory mixed-methods design to examine factors for psychiatric admissions following the first UK 2020 lockdown compared to the same time periods in 2019 and 2018. RESULTS: Themes of psychopathology, risk, social stressors, community treatment issues, and physical health concerns were generated. The mean number of codes per case was 6.19 (s . d. = 2.43), with a mean number of categories per case of 3.73, (s. d. = 0.98). Changes in routines and isolation were common factors in the study year; accommodation and substance abuse were more prominent in the control year. Relationship stressors featured strongly in both groups. There were significantly more women (χ2(1, N = 98) = 20.80, p < 0.00001) and older adults (χ2(1, N = 98) = 8.61, p = 0.0033) in the study group than the control. Single people, compared to those in a relationship (χ2(1, N = 45) = 4.46, p = 0.035), and people with affective disorders compared to psychotic disorders ((χ2(1, N = 28) = 5.19, p = 0.023), were more likely to have a COVID-19 related admission factor. CONCLUSIONS: Early stages of the COVID-19 pandemic amplified pre-existing psychosocial vulnerabilities with a disproportionate psychiatric admissions impact on the mental health of women, older adults and those with affective disorders.

Laboratory validation studies in Ki-67 digital image analysis of breast carcinoma: a pathway to routine quality assurance.

Ki-67 proliferative index (PI) has prognostic and predictive value in invasive breast carcinoma (IBC), but clinical uptake has been hampered by suboptimal accuracy, reproducibility and standardisation. Published guidelines have addressed pre-analytical and analytical factors to improve Ki-67 PI utility; however, practicalities of ongoing monitoring of Ki-67 PI quality in IBC reporting have not been established. We aimed to evaluate the internal and external quality of our established digital Ki-67 PI IBC reporting practice at a tertiary institution. In the 5 years since initial validation work, we've completed a series of internal and external quality assurance (QA) projects: (1) an interobserver agreement study, (2) a two site interlaboratory agreement study, (3) determination of the error of our Ki-67 results, (4) an audit of the year-to-year Ki-67 values, (5) an audit of Ki-67 in neoadjuvant chemotherapy (NAC) treated cases, and (6) comparison of our Ki-67 datasets with similar published datasets. There was excellent concordance (intra-class correlation = 0.98) and good agreement [kappa (κ) = 0.76-0.96] between pathologists, excellent concordance [Pearson correlation (R) = 0.94] and very good agreement (κ = 0.80) between laboratories and excellent concordance (R = 0.92-0.95) and good agreement (κ = 0.67-1.0) over time for our Ki-67 results. No significant difference was observed in Ki-67 data from year-to-year. Expected associations with clinico-pathological prognosticators, pathological complete response following NAC and mitotic index were evident. The median Ki-67 values from the overall and NAC treated datasets were within the range reported in other studies, and our data could be separated into similarly proportioned 'high' and 'low' Ki-67 PI groups when dichotomised as per protocols in other studies. Collectively, our work provides evidence of adequate internal and external quality control for our digital Ki-67 PI IBC reporting protocols. Given the paucity of formal Ki-67 QA programs, our approach could be emulated, and results compared between laboratories as a framework for internal and external Ki-67 QA.

Unusual paediatric spinal myxopapillary ependymomas: Unique molecular entities or pathological variations on a theme?

Ependymomas are the commonest type of spinal glioma which represent a group of relatively benign tumours. Myxopapillary ependymoma (MPE) is a common variant found within the distal spinal cord around the conus. These two entities are clearly differentiated on the basis of their characteristic histological and molecular features. Rare variants of MPE's are described in the literature to have the propensity to metastasise and grow in extraspinal locations despite appearing histologically identical to their more benign relatives. Here, we describe two unusual cases of MPE and utilise DNA methylation analyses to compare their molecular signatures with known molecular subtypes of ependymoma in an attempt to distinguish whether these tumours represent a unique subset of disease.

Paediatric cutaneous adnexal tumours: a study of 559 cases.

Cutaneous adnexal tumours encompass a wide group of lesions with apocrine, eccrine, follicular, sebaceous and mixed differentiation. The large majority are benign and represent sporadic lesions, though malignant forms are occasionally encountered and some cases develop in the setting of inherited tumour syndromes. Accurate histological classification can be difficult as there are numerous histological appearances, many of which are individually uncommon, and complex, overlapping and historically variable nomenclature is typical. The aim of this study was to review and classify the spectrum of cutaneous adnexal tumours seen in patients 18 years of age and under in two major tertiary centres over a 20 year period. A total of 559 cases were included, with 60% occurring in female patients. The large majority (87%) occurred in the head and neck region and were benign. Only one (0.2%) was malignant. The original diagnosis was supported by histological review in 99% of cases of pilomatricoma reviewed, but in only 71% of non-pilomatricoma cases reviewed. The most common lineage was follicular (97%), with pilomatricoma accounting for the large majority of lesions. Predominant glandular/ductal differentiation was seen in 3% of cases, with no tumours showing predominant sebaceous differentiation.

Low risk, but not no risk, of umbilical hernia complications requiring acute surgery in childhood.

AIMS: Umbilical hernias are a common finding in the paediatric community, with a preponderance to affect Afro-Caribbean and premature children. The rate of incarceration varies greatly between populations. Therefore, it is valuable to obtain some Australian data on this topic. METHODS: We undertook a retrospective study of the records of all patients who underwent umbilical hernia repair over a 12-year period of between October 1999 and May 2012 at Princess Margaret Hospital. From this group, all patients that had an umbilical hernia repair for reason of acute complication were identified and analysed for age, ethnicity and co-morbidities. RESULTS: Between October 1999 and May 2012, 433 umbilical hernias were repaired at Princess Margaret Hospital, five of which were as the direct result of an acutely complicated umbilical hernia. The mean age of hernia repair was 5 years old, and the mean age of acute complication was 5 years old. Out of the patients with acutely complicated umbilical hernia, there were no Afro-Caribbean patients, and one was premature complicated by hyaline membrane disease and broncho-pulmonary dysplasia. CONCLUSIONS: Western Australia has an incidence of acutely complicated umbilical hernia requiring operative intervention of 1:3000 to 1:11,000. On an international scale, this is low, and studies with similar incidence do not advocate for immediate repair of all identified umbilical hernias. The authors believe repair should be guided by patient and guardian, but if there is an episode of incarceration, acute repair is advised.