Taking guidance from parents involved in a longitudinal birth cohort - the ROLO family advisory committee.

BACKGROUND: The ROLO Study (Randomised cOntrol trial of a Low glycaemic index diet in pregnancy to prevent macrosomia) was a randomised control trial conducted between 2007 and 2011 to examine if a low glycaemic index (GI) diet could reduce the incidence of macrosomia. The ROLO Family Advisory Committee is a self-selected group of parents who are involved in the longitudinal follow-up of the ROLO Study. The committee was established in 2017 and the goal is to achieve a partnership between ROLO families and researchers, leading to improved research quality, relevance, and outcomes. This research method is termed "Public and patient involvement (PPI)" and describes how researchers collaborate and engage with the public in order to make research more relevant to them. METHODS: The ROLO study mothers and children have been prospectively followed-up at multiple time points post-pregnancy. In October 2017, all women were invited to join the ROLO Family Advisory Committee via email or via advertisement on the ROLO Study Facebook page. Fathers and other guardians of the study children were also invited to join. Two annual meetings with the research team and parents were held in 2018 and 2019. The meetings were recorded, transcribed verbatim by researchers, and thematically analysed. RESULTS: Parents provided opinions on the areas they felt should be explored within the ROLO study using information that was collected up to the current follow-up point. They also shared views on research interests which were of importance to them. These topics included; child mental health, fussy eating in childhood and healthy eating policies in schools. Mothers were much more concerned about factors which influenced their child's health rather than their own. Incorporating an element of PPI to this study was found to be a positive learning experience for participants and researchers. CONCLUSION: The involvement of parents has enriched the research agenda at the UCD Perinatal Research Centre. We will continue to engage with the parents of the ROLO Study and plan to involve the children to explore their opinions at the next opportunity.

Complete spontaneous regression of metastatic merkel cell carcinoma: a case report and review of the literature.

Merkel cell carcinoma (MCC) is a rare aggressive primary cutaneous neuroendocrine neoplasm with a high rate of recurrence and metastasis. We report a case of a 94-year-old woman who experienced complete spontaneous regression of metastatic MCC. Nine months after complete excision of the primary MCC on her left eyebrow, metastatic MCC was confirmed with a fine-needle aspiration of a 4-cm mass on the left side of her neck. Three months later the mass had reduced in size to 2 cm and a neck dissection was performed. Her submandibular gland, thoracic duct and 25 lymph nodes were negative for MCC. Two of the lymph nodes, the larger measuring 1.3 cm, contained extensive amounts of fibrosis, with accumulation of macrophages and other chronic inflammatory cells. The literature documents 6 similar cases of complete spontaneous regression of metastatic MCC. The mechanism for regression is not well understood and is thought to involve T-cell-mediated immune response and apoptosis.

Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof.

A significant proportion of primary neuroendocrine cell carcinomas of the skin (Merkel cell carcinomas [MCCs]) have been reported to occur in intimate association with malignant epithelial neoplasms, mainly squamous cell carcinomas. In addition, divergent differentiation within these tumors, particularly of squamous and eccrine types, is not infrequent. This expanded morphologic spectrum of MCC calls for evaluation of potential biologic implications of the phenotypic diversity and begs reconsideration of the histogenesis of the lesion. The current retrospective review of 29 cases of primary cutaneous neuroendocrine cell carcinoma aims to address these issues by integrating new information with that which is extant. Eleven tumors were associated with evolving or established cutaneous carcinomas: 2 actinic keratoses, 5 Bowen's disease, 3 superficial squamous cell carcinomas, and 1 basal cell carcinoma. Two combined squamous-neuroendocrine tumors occurred in recipients of solid organ transplants, and another developed in a Marjolin's ulcer at the site of a previous burn. Squamous and/or adnexal differentiation within the dermal component of the tumor was observed in 4 instances and was significantly associated with MCCs in intimate association with another cutaneous carcinoma. The outcome of the group as a whole is similar to that recorded in previous series of MCC, with local recurrence in 32% of cases and death caused by the neoplasm in 28%. Only 52% of the patients were alive with no history of metastasis at follow-up. No significant difference in outcome was observed between the patients with pure MCCs and those with MCCs in combination with another cutaneous carcinoma.

Merkel cell carcinoma of the abdominal wall.

Merkel cell carcinoma is a rare highly malignant tumour. There have been previous descriptions of the CT appearances of this tumour, but to our knowledge this is the first MRI description. MRI may be a more sensitive method of initial evaluation of the local extension of the primary tumour.

Multiple eruptive milia: report of a case, review of the literature, and a classification.

A 71-year-old man presented with an acute onset of multiple white papules on the face and chest. Histologic sections demonstrated multiple milia. The rare condition of multiple eruptive milia occurs when crops of milia develop suddenly on the face and upper trunk. Rare isolated cases have been reported; however there has not been a review of these cases or an attempt to classify them. The authors report an additional case, review the literature, and suggest a classification of multiple eruptive milia.

Subcutaneous dirofilariasis in Nova Scotia.

A case of dirofilariasis in a 78-year-old woman from Nova Scotia is described along with the histological findings and the basis of identification of the parasite. The patient developed a subcutaneous nodule, which was excised. Dirofilaria ursi and ursi-like nematodes are a rare cause of subcutaneous nodules. This is the first time dirofilariasis has been diagnosed in an adult in Atlantic Canada.

Histopathology in erythroderma: review of a series of cases by multiple observers.

This study examines the utility of objective histopathological studies in the evaluation of adult patients with erythroderma. A series of 56 skin biopsies, from 40 erythrodermic patients, was reviewed sequentially by 4 Canadian dermatopathologists who were unaware of clinical details of the cases. The final diagnosis (gold standard), in each instance, had already been determined by others, based on clinicopathologic data and response to therapy. Direct comparison revealed that the mean accuracy of the histopathological diagnoses was 53% (range: 48-66%), a favorable result in view of the difficulty of the task at hand. Additional points of information which evolved from the study are as follows: (i) identification, by microscopy alone, of spongiotic dermatitis, cutaneous T-cell lymphoma and psoriasis, as underlying causes of erythroderma was more successful than that of drug eruptions and pityriasis rubra pilaris; (ii) the epidermotropism which characterizes cutaneous T-cell lymphoma may be mistaken for inflammatory interface changes seen in drug eruptions and vice versa, thus constituting a pitfall in diagnosis; (iii) finally, it appears that submission of multiple simultaneous biopsies, rather than a single specimen, from patients with erythroderma would be likely to enhance the accuracy of histopathological diagnosis.

Eruptive xanthomata with urate-like crystals.

The microscopic manifestations of eruptive xanthomata are variable and although they are most frequently characterized by aggregations of foamy macrophages in the dermis, they can, on occasion, simulate granuloma annulare. We have recently encountered a further unusual histopathological variant of eruptive xanthomata in 3 skin biopsies from 2 patients with hypertriglyceridemia. The lesions had a granuloma annulare-like pattern at low magnification, the exceptional feature being their content of polarizable, needle-shaped crystals. These bore a strong resemblance to monosodium urate monohydrate and displayed negative birefringence under polarized light. In the case of each patient, an initial pathological diagnosis of gout was rendered, and the true nature of the lesions came to light only after clinicopathologic correlation. While it is clear that the chemical composition of these crystals requires further study, recognition of this microscopic variant of eruptive xanthomata should help to reduce errors in diagnosis.

The specificity of histopathology in erythroderma.

Conflicting views about the diagnostic value of skin biopsy in the investigation of erythrodermic patients are extant. The objective of the present study was to establish the frequency with which a correct diagnosis can be based on histopathological assessment alone. This was achieved by comparison of the "blinded" microscopic diagnosis with the final diagnosis (based on combined clinico-pathologic parameters and response to therapy). In a retrospective review of 56 skin biopsies from 40 patients with erythroderma, we found a positive correlation between the pathological diagnosis and the final diagnosis in 66%; furthermore, when the microscopic characteristics observed in different diagnostic categories were assessed, these proved to simulate those seen in conventional manifestations of the various underlying diseases but tended to be subtle in the setting of erythroderma. We conclude that, despite the homogeneity of the clinical expression of erythroderma, diagnostic histopathological features of the underlying disease are retained in the majority of cases.

Cutaneous sarcoidosis and foreign bodies.

A histopathological diagnosis of sarcoidosis is, by convention, one of exclusion and is reached only when other potential causes of granulomatous disease, such as foreign bodies, are eliminated. We report herein three cases of systemic sarcoidosis with cutaneous manifestations of the disease, in which polarizable foreign particles were associated with the granulomata in the skin. We submit (a) that a granulomatous foreign body reaction and sarcoidosis are not mutually exclusive, (b) that particulate foreign matter may actually serve as a nidus for granuloma formation in sarcoidosis, and (c) that the occasional presence of extraneous material within the granulomata of sarcoidosis requires greater recognition by pathologists.

Cognitive impairment and autoantibodies in systemic lupus erythematosus.

Nervous system involvement in systemic lupus erythematosus (SLE) includes a wide array of manifestations some of which have been associated with specific autoantibodies. These include reactivity to surface neuronal and lymphocyte antigens, ribosomal P and cardiolipin. The aim of the present study was to examine the association between cognitive abnormalities and these autoantibodies in an unselected female population of SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared to 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Circulating antineuronal antibodies were measured by indirect immunofluorescence using human neuroblastoma cell lines IMR-6 and SK-N-SH. Lymphocytotoxic antibodies were measured by microcytotoxicity. Antibodies to ribosomal P and cardiolipin were measured by ELISA. Antineuronal antibodies were detected in 34%, lymphocytotoxic antibodies in 47%, anti-P antibodies in 17% and anticardiolipin antibodies in 24% of patients. In the cognitively impaired and unimpaired SLE patients there was no significant difference in the prevalence of antineuronal antibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%), anti-P antibodies (20 vs 17%) or anticardiolipin antibodies (7 vs 29%). The titre and isotype of autoantibodies were also similar in both groups. These results suggest that autoantibodies which have previously been associated with nervous system manifestations of SLE are not likely to be directly involved in the pathogenesis of cognitive dysfunction.

Brain pathology in systemic lupus erythematosus.

Brain pathology was documented in 10 patients with systemic lupus erythematosus (SLE), 7 of whom had clinical neuropsychiatric SLE prior to death. This was manifested by seizures (5 patients), organic brain syndrome (3 patients) and psychosis (2 patients). Multifocal cerebral cortical microinfarcts, associated with microvascular injury, were documented in 4 patients and in our study constituted the predominant histopathologic abnormality attributable to SLE. Changes of a healed vasculitis in medium sized leptomeningeal vessels were seen in 1 case. Agreement between the clinical and pathologic classification of neuropsychiatric SLE was observed in 7/10 (70%) cases and the strongest association was between the presence of cerebral microinfarcts and seizures (4/5 patients, p less than 0.05). No correlation was observed with anticardiolipin, anti-P, lymphocytotoxic and antineuronal antibodies.

Human immunodeficiency virus-related Kaposi's sarcoma of the appendix and acute appendicitis. Report of a case and review of the literature.

We describe a case of acute appendicitis precipitated by human immunodeficiency virus-related Kaposi's sarcoma of the appendix. This presentation in an otherwise asymptomatic homosexual man led to the establishment of a diagnosis of acquired immunodeficiency syndrome. Immediate follow-up revealed multicentric gastrointestinal involvement by Kaposi's sarcoma, and skin involvement ensued in 2 months. Salient features of this case and two other similar reports in the literature are highlighted.

Auerbach's myenteric plexus. A possible site of origin for gastrointestinal stromal tumors in von Recklinghausen's neurofibromatosis.

We present a case of multiple benign spindle cell tumors of the jejunum in a patient with von Recklinghausen's neurofibromatosis and describe the light-microscopic, immunohistochemical, and ultrastructural features of these lesions. Two small spindle cell nodules were located in the region of Auerbach's myenteric plexus and a third larger tumor produced a subserosal mass. The immunohistochemical profile of these tumors revealed that they were actin and S100-protein negative but positive for neuron-specific enolase. At the ultrastructural level, the tumors recapitulated features of Auerbach's plexus. These lesions are similar to previously described gastrointestinal autonomic nerve tumors, and we propose that this may be the site of origin of enteric stromal tumors in von Recklinghausen's neurofibromatosis.

Desmoplastic malignant melanoma. A clinicopathologic study of 14 cases.

Clinical and pathologic details in 14 cases of desmoplastic malignant melanoma were reviewed. The study group included ten men and four women with a median age of 58 years. Anatomic locations such as the head and neck area (four cases), limbs (five cases), and trunk (five cases) were involved with equal frequency. Follow-up information (median period, 4.6 years) was available for 12 patients, of whom four are alive and disease free, six have had local tumor recurrence, and two have died of their disease. Histologically, these lesions consisted of a malignant fibroblastic skin tumor intimately associated with a superficial melanoma (ten cases) or melanocytic dysplasia (four cases) that often extended deeply to the subcutaneous fat. Helpful diagnostic features included the presence of neurotropism, a lymphocytic infiltrate, and unusual patterns of triangular and periadnexal lamellar fibroplasia. Of the immunohistochemical markers employed, antisera to S100 protein and vimentin yielded the most consistent positive results. Immunostaining with NK1/C-3 (antimelanoma monoclonal antibody) was not helpful. Ultrastructural evidence of fibroblastic and schwannian differentiation was seen. We conclude that the altered morphologic melanomas is associated with a relatively favorable prognosis and believe that careful attention to light microscopic detail with immunohistochemical and electron microscopic assistance will elucidate the diagnosis in most cases.

Massive osteolysis in the hand and response to radiotherapy.

We report a case of severe bony and articular destruction in the hand of a 62-year-old woman, secondary to localized vascular proliferation. A short course of radiotherapy (total dose 3000 rad) resulted in rapid relief of symptoms and prevention of further osseous destruction over a 6-year followup period.