Carcinosarcoma of the uterus with melanocytic differentiation

Carcinosarcomas (CSs) are rare biphasic neoplasms of the female genital tract, with the presence of malignant epithelial and mesenchymal components. The occurrence of non-epithelial or non-mesenchymal differentiations in CSs is extremely rare. A case of a 54-year-old woman with a history of treatment for breast carcinoma is reported. The patient presented with a uterine tumor showing histological, immunohistochemical, and ultrastructural features of an extremely rare CS, with signs of melanocytic differentiation. The lesion was a 7.0 x 5.6 cm polypoid tumor mass arising from the endometrium and metastasizing in the abdominal cavity as a malignant melanoma - the most aggressive component of CS. Despite adjuvant chemotherapy, she died 8 months after the initial diagnosis due to the metastatic spread of CS. In line with current knowledge, we assess the melanocytic differentiation as one of a hypothetic differential line with the ability of multidirectional stem cell differentiation. We discuss a possible pathogenesis of this lesion and the role of tamoxifen in the tumor development as well. To the best of our knowledge, only one case of uterine CS with melanocytic differentiation has been reported in the English literature.     

A case report of a patient with inoperable primary diffuse leptomeningeal melanomatosis treated with whole-brain radiotherapy and pembrolizumab

Rationale:Primary diffuse leptomeningeal melanomatosis (PDLM) is a rare disease that affects melanocytes in the leptomeninges. There is very limited data on the efficacy of immunotherapy in this setting.Patient concerns:A patient (23 years old) was diagnosed with PDLM. Histologically, atypical melanocytic cells were also observed.Diagnosis:Immunohistochemistry showed positivity for S100 protein, NKiC3, and vimentin, and negativity for Melan-A and HMB-45, with a proliferation index of 30%. Extracranial disease was excluded using dermatological and other examinations, including positron emission tomography/computed tomography with ¹⁸F-fluorodeoxyglucose.Interventions:The patient was treated with whole-brain radiotherapy (10 fractions to a total dose of 30 Gy) concomitantly with pembrolizumab and then continued with immunotherapy until disease progression with a maximum effect of partial remission on magnetic resonance imaging scans.Outcomes:Progression-free survival was 6.0 months and overall survival 6.5 months.Lessons:This is one of the few case reports of an adult patient with this rare malignancy being treated with a programmed death-1 inhibitor with partial response. Immunotherapy in metastatic PDLM may be a reasonable therapeutic option.     

Long-term treatment with mesalazine in patients with symptomatic uncomplicated diverticular disease

The aim of this work was to compare the recurrence of diverticulitis during a 5-year follow-up in a population of patients affected by symptomatic uncomplicated diverticular disease (SUDD), taking either 800 mg of mesalamine b.i.d for 10 days every month or no 5-ASA. Sixty-seven consecutive patients affected by SUDD followed-up every 6 months for 5 years. All patients in this group (M-group) were requested to consume mesalamine 800 mg b.i.d for 10 days every month. A control group (C-group) of 82 subjects with SUDD allocated in an institution for the elderly and taking no 5-ASA medications was also followed-up for the same period. As a result in the M-group 14.9% of patients did not complete the follow-up, and diverticulitis developed in two patients (4%; 95% CI 1.1–13.5). In the C-group 6.1% patients did not complete the follow-up, and diverticulitis developed in 8 patients (10.4%; 95% CI 5.4–19.2). The difference between the two groups was not significant (difference = −6.4%; 95% CI −15.6 to 4.3; log rank test: p = 0.1256). Cyclic treatment with mesalazine seems to be clinical, although not statistically effective in reducing the incidence of diverticulitis. In future well-designed RCTs are necessary to demonstrate the therapeutic gain of the use of mesalazine, if any, in the management of patients with SUDD.     

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.     

Myoid (Muscular) Hamartoma of the Breast: Case Report and Review of the Literature

BACKGROUND: Myoid (muscular) hamartoma (MH) of the breast is a rare benign tumour-forming lesion composed of differentiated mammary glandular and stromal structures, fatty tissue, and areas of smooth muscle. It is considered to be a variant of mammary hamartoma. CASE REPORT: We report the case of a 46-year-old woman with MH, and provide a literature review explaining the origin of smooth muscle cells. Histologically, the tumour consisted of fibrolipomatous stroma containing ductal and lobular structures of the mammary gland located mainly at the tumour borders. The glandular structures showed signs of micro- and macrocystic changes, apocrine metaplasia, and adenosis. The dominant feature was the presence of a fascicular formation of spindle cells, predominantly in central parts, with incursion between glandular structures. Immunohistochemically, foci of smooth muscle tissue were positive for desmin, smooth muscle actin, and h-caldesmon. Oestrogen and progesterone receptors (PR) showed positive expression which was markedly higher for PR. There was negative expression of CD34, S-100 protein, and CD10. CONCLUSIONS: The origin of smooth muscle cells in MH is unknown. However, it is presumed to be derived from hormonally responsive breast stromal cells by smooth muscle metaplasia, based on evidence of hormone receptor expression in the lesion.     

The role of clinical and metabolic factors in the genesis and development of diabetic retinopathy

AIM: Diabetes is a complex polygenic, auto-aggressive disease caused by many different factors. Diabetic retinopathy is the leading cause of new cases of blindness in people aged between 25 and 65 years (working population) in industrialized countries. The aim was to determine whether disease duration, diabetes type and blood concentrations of some metabolites may be risk factors for the genesis and development of diabetic retinopathy. METHODS: This retrospective study included 402 diabetic patients from the Split-Dalmatia County. Laboratory testing included blood glucose, glycosylated hemoglobin A1c, total cholesterol, HDL and LDL cholesterol fractions, and apolipoprotein A and B concentrations. DISCUSSION: The incidence of diabetic retinopathy is increasing in our region, with nonproliferative form as the most common type. Women suffer more frequently from diabetic retinopathy, those aged 60 being at the highest risk. The genesis of diabetic retinopathy is directly correlated with the type and duration of diabetes. Changes in total cholesterol concentration, especially LDL fraction, and apolipoproteins A and B (especially B) indicate an increased relative risk of developing diabetic retinopathy. CONCLUSION: In our opinion, testing of glycosylated hemoglobin, HDL and LDL cholesterol fractions, and apolipoproteins A and B in the standard follow-up protocol for diabetic patients would significantly contribute to the prevention and reduction of diabetic retinopathy as the most common and most difficult diabetic eye complication.     

Y-chromosomal short tandem repeat haplotypes in southern Croatian male population defined by 17 loci

Aim

To define the Y-chromosome genetic structure in a sample of men from southern Croatia.

Methods

Blood samples were collected from 166 unrelated healthy men from southern Croatia at the Department of Forensic Medicine and Biochemical Laboratory of University Hospital Split between 2004 and 2007. Genomic DNA was extracted using the standard procedures. Seventeen Y-chromosome short tandem repeat (Y-STR) polymorphic loci (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385, DYS393, DYS391, DYS439, DYS635, DYS392, GATAH4, DYS437, DYS438, and DYS448) were analyzed using AmpFlSTR Yfiler Polymerase Chain Reaction Amplification Kit.

Results

We observed 152 different haplotypes. Total haplotype diversity was 0.997289 and 141 haplotypes (84.49%) were unique. The most common haplotype was shared by only 4 men in the study sample. The locus diversity ranged between 0.21292 for DYS392 and 0.75546 for DYS439 locus.

Conclusion

The Y-chromosome structure in men from southern Croatia is very diverse. Combination of Y chromosome 17 STR loci may be used as a powerful tool for individual identification and parentage analysis in the southern Croatian male population.Except for occasional mutations, the major part of the male-specific Y chromosome is inherited from father to son unchanged, as a haplotype of physically linked markers, because it is not involved in recombination with X chromosome. Genotyping of this Y-specific non-recombining region (NRY) can be used to track paternal lineage, since all patrilineal relatives share the same NRY haplotype. Thus, NRY multiple marker genotyping is used to infer paternity when the putative father is not available for DNA analysis or to validate biological relationships when one of the relatives is unable to take part in the DNA typing test. NRY multiple marker genotyping is also used in forensic casework to identify a male perpetrator’s DNA in mixed samples with an excess of female victim’s DNA. In such cases, it is a better option than polymerase chain reaction (PCR)-based amplification of female autosomal DNA markers or potential overlap of autosomal DNA marker profiles (1).Genotyping small tandem repeats (STR) or microsatellite repeats or simple sequence repeats represents one of the most reliable and reproducible DNA profiling methods in forensic investigation. Genotyping multiple Y-chromosomal STR (Y-STR) markers is widely used in forensic and population studies in spite of its lower discrimination potential in comparison with autosomal STR genotyping. The constantly growing number of Y-STR markers available for forensic, evolutionary, and population studies increases Y-haplotype differentiation potential in distinct male populations (2).The aim of our study was to use 17 Y-STRs to define the genetic structure of Y chromosome in a sample of men from southern Croatia. Our results may contribute to the development of a population database that may be used to estimate the haplotype frequency, ie, the probability that two or more unrelated men share the same Y-STR haplotype. Furthermore, a Y-STR haplotype database for Croatian population may serve for assigning geographic origin to male individuals, since Y chromosomal markers are more prone to genetic drift than autosomal markers due to smaller effective population size, which enhances geographically-based differentiation of Y lineages.     

Cutaneous angiosarcoma following conservative surgery and radiotherapy for breast carcinoma. A case report

Breast angiosarcomas (AS) are very rare neoplasms, which can be divided into primary (or sporadic), and secondary AS, the latter arising either on the base of lymphoedema after mastectomy (so called AS with Stewart-Treves syndrome- ASSTS), or skin AS after breast conservation surgery with subsequent radiotherapy for breast cancer (KPRAS). The authors present a case of a 55-year-old female patient with a 17mm tumour in nipple region, developing 8 years after primary diagnosis of tubulolobular carcinoma of the breast which was treated by breast conservation surgery and radiotherapy. A probatory bioptic examination of the lesion proved well-differentiated KPRAS. The patient underwent mastectomy. The authors analyse the basic clinical and morphological features of KPRAS, which distinguish it from other forms of AS, e.g. occurrence in older age, shorter period of latency after radiation therapy when compared to ASSTS, absence of lymphoedema, and rare involvement of the breast tissue. Prognosis of this entity is very poor; today the most reliable prognostic marker is histological grading. However, it will be needed to assess in the future new indicators of prognosis of patients with this rare disease.