Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.

Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment.

Aim: To investigate the effect of tadalafil in rats administered with daily dutasteride.Methods: Twenty-four Sprague-Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D + T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined.Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D + T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p = .01) whereas group D + T had the highest iNOS (p<.001). ELISA revealed similar outcomes in terms of NOS enzyme isoform levels. The mean of smooth muscle to collagen ratio was the lowest in group D (p < .001) and it was similar among group C and group D + T (p = .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D + T (p>.05). Group D and group D + T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D + T.Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis.

The Controversy of Surgical Intervention for Anal Canal Duplication in Children.

OBJECTIVE: Since the first definition of anal canal little has been discovered about the etiology of this rare condition. We present four asymptomatic cases of anal canal duplication with diverse clinical and surgical findings. METHODS: A retrospective chart review was performed on four infants presenting with asymptomatic anal canal duplication, born between 2014 and 2016. Clinical characteristics and pathologic findings of patients either by radiological imaging or pathology were evaluated. The primary outcome measure was the complications. RESULTS: All patients were followed-up with physical examination and ultrasound for a mean of 3.5±1.0 years, lastly seen at the beginning of 2018. The female to male ratio was 3:1. Duplicate anal canal length varied between 12-20mm, and two of the four patients had a presacral cystic mass confirmed as a tail gut cyst following surgery. At follow-up, none of the patients had developed symptoms related to anal canal duplication, regardless of whether they had surgical intervention. CONCLUSION: Though surgical management is the preferred treatment for anal canal duplication, it seems that patients who do not undergo surgery might remain free of symptoms, suggesting that surgical intervention may be unnecessary.

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea.

OBJECTIVE: The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. METHODS: A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. RESULTS: In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). CONCLUSION: We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.

Peripheral neuropathy in Tangier disease: A literature review and assessment.

Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic neuropathies characterized by marked deficiency of high-density lipoproteins and accumulation of cholesterol esters in various tissue resulting from reverse cholesterol transport deficiency. We report a case of a patient with TD with multifocal demyelinating neuropathy with conduction block who presents with winging scapula, tongue, and asymmetric extremity weakness. We also present a review of all studies published from 1960 to 2017 regarding peripheral neuropathy in TD. Our search identified 54 patients with TD with peripheral neuropathy. Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%), and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most common (40.7%) clinical manifestation in these patients. The pattern of electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more predominant in the upper extremities than in the lower extremities and (2) slowing of motor nerve conduction was more prominent in the intermediate segment than in distal nerve segments. The sural-sparing pattern was present in 34.6% and conduction block was present in 11.5% of the patients. Our literature review and our case showed the clinical spectrum of TD neuropathy is quite wide and that it should be considered in the differential diagnosis of non-uniform demyelinating neuropathies.

Long-term outcomes in pediatric appendiceal carcinoids: Turkey experience.

The tendency of non-operative management of appendicitis let us explore the natural history of appendiceal carcinoids, compare them with appendicitis patients, and determine the possibility of deciding the extent of the surgery and post-operative follow-up on behalf of the intraoperative findings. A retrospective review was performed of patients with appendicitis between 2009 and 2017. Of 2781 patients, 10 (0.36%) were diagnosed with appendiceal carcinoids. Sixty percent were female with an average age of 13.10 ± 1.73. The mean tumor size was 0.97 ± 0.34 cm with 70% located at the tip. Majority had an insular pattern (n = 9), six had subserosal fat tissue invasion, one had extension to mesoappendix, one had vascular invasion, and two had lymphatic invasion. The average mitotic index was 3.20 ± 1.40/50HPF, and Ki 67 activity was 3 ± 1.7%. The mean follow-up period was 66.40 ± 25.92 months. Patients were further evaluated with ultrasonography (n = 10), CT (n = 3), and MRI (n = 10). Serum markers including chromogranin (n = 9), NSE (n = 6), and 5-HIAA (n = 6) were normal. None required further treatment and had any symptoms of carcinoid syndromes or recurrences post-operatively.Conclusion: Other than appendectomy, no additional surgery or follow-up is required in appendiceal carcinoids less than 1.5 cm in size, regardless of the lymphoid or vascular invasion. What is Known: • The treatment of patients with a 1-2-cm tumor is not clear in both the pediatric and adult populations, and additional resection is needed. • Patients are monitored post-operatively with radiological and/or biochemical testing. What is New: • Appendectomy is curative for tumors less than 2 cm. • No additional surgery or follow-up is required in appendiceal carcinoids less than 1.5 cm in size regardless of the lymphoid or vascular invasion.

Is submucosal fat injection effective in atrophic rhinitis? An experimental animal study.

Atrophic rhinitis (AR) is a disease characterized by the extensive dilatation of the nasal cavity and atrophy of the mucosa, submucosa and bone tissue. Its etiological factors are unknown. There is not a satisfying treatment yet and the treatment of the functional impairment in the atrophic cells is still subject to investigation. The objective of this study is to determine at the histopathological level the possible effects of the submucosal fat injection in an experimental model of AR. 12 albino Wistar-Hannover male rats were included in the study. AR was induced with the Pasteurella multocida toxin, which was diluted with saline. As one of the rats died during the study, it was excluded from the evaluation. The right nasal cavities of all rats (11 nasal cavities) were defined as the control group (Group 1). Fat tissue obtained from the abdominal area was injected in the seven left nasal cavities (Group 2). All injections, which were done to the abdominal regions were also done in the left nasal cavities of the remaining four rats, which constituted the sham group (Group 3). After 14 days, all rats were decapitated and the squamous metaplasia and keratinization in the superficial epithelium, degeneration, vacuolar changes in the basal layer, congestion, inflammatory infiltration, vascular proliferation and glandular atrophy in the submucosa are histopathologically classified. The results were analyzed with statistical methods. Although glandular atrophy was significantly regressed in the fat injection group (Group 2) compared to other groups (p < 0.05), the remaining parameters did not show any significant difference among these three groups. The histopathological effect of the fat injection was modest. We concluded that fat injection treatment has no or at the most a very limited effect in the treatment of atrophic rhinitis.

Polypropylene mesh for nasal septal perforation repair: an experimental study.

The aim of this study is to determine the effectiveness and biocompatibility of polypropylene mesh for the repair of nasal septal perforations in an animal model on rabbits. A full-thickness nasal septal perforation with a diameter of nearly 10 × 10 mm was created on 12 rabbits, and then the perforation was reconstructed with two different methods. We used mucosal flaps and polypropylene mesh as an interpositional graft in group 1. Only mucosal flaps were used for reconstruction and are identified as group 2. After 4 weeks, we removed the nasal septum of the rabbits and performed histopathological examinations for acute rejection, infection, inflammatory response, fibrosis, and granuloma formation. We found perforation closure rates of 75 and 25 % in groups 1 and 2, respectively. Inflammatory response was seen in all specimens of group 1 (100 %). The inflammatory response was +1 in five of the specimens (62.5 %), +2 in one specimen (12.5 %), and +3 in two specimens (25 %). Mild fibrosis around the mesh was detected in four specimens (50 %), medium-level fibrosis was detected in one (12.5 %), and no fibrosis was detected in three (37.5 %). Severe fibrosis was not seen in any specimens. The foreign-body reaction was limited to a few giant cells, and granuloma formation was seen in two specimens (25 %). The propylene mesh showed excellent biocompatibility with the septal mucosa, and it can, therefore, be used for the repair of septal perforation as an interpositional graft safely.

Evaluation of the endocrine-disrupting effects of homosalate (HMS) and 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) in rat pups during the prenatal, lactation, and early postnatal periods.

Homosalate (HMS) and 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) are ultraviolet filters. We aimed to investigate the effects of dermal exposure to HMS and OD-PABA during the prenatal, lactation, and early infancy periods on pubertal development and thyroid function in male and female rats. The thyroid glands, uteri, testes, prostate glands, and seminal vesicles were excised and weighed, the reproductive organs were analyzed histologically, and the serum hormone levels were measured. In the prenatal period, the thyroxine (T4) levels increased in the female rats in the exposed groups ( p < 0.05); the thyroid weights, reproductive organ weights, and gonadal hormone levels were not altered. In males, the testosterone levels decreased ( p < 0.05), but the thyroid weights, T4 levels, prostate, and testis weights were not changed. In the lactation period, the weights of the thyroid glands increased in the exposed female groups ( p < 0.05), but the T4, gonadal hormone levels, and reproductive organ weights were not changed. In the males, the thyroid gland weights, T4 levels, reproductive organ weights, and gonadal hormone levels were not changed. During infancy, the thyroid gland weights increased in the female rats in the exposed groups ( p < 0.05), but the T4 levels, gonadal hormone levels, and reproductive organ weights were not affected. In the male rats in the exposed groups, the T4 levels were increased ( p < 0.05), but the thyroid and reproductive organ weights, gonadal hormone levels were not affected. Organ histopathology was not affected in all groups. HMS and OD-PABA do not have endocrine disruptor effects on thyroid function and the pubertal development of female and male rats.

Effects of ozone (O3) therapy on cisplatin-induced ototoxicity in rats.

The aim of this study is to investigate the effect of rectal ozone and intratympanic ozone therapy on cisplatin-induced ototoxicity in rats. Eighteen female Wistar albino rats were included in our study. External auditory canal and tympanic membrane examinations were normal in all rats. The rats were randomly divided into three groups. Initially, all the rats were tested with distortion product otoacoustic emissions (DPOAE), and emissions were measured normally. All rats were injected with 5-mg/kg/day cisplatin for 3 days intraperitoneally. Ototoxicy had developed in all rats, as confirmed with DPOAE after 1 week. Rectal and intratympanic ozone therapy group was Group 1. No treatment was administered for the rats in Group 2 as the control group. The rats in Group 3 were treated with rectal ozone. All the rats were tested with DPOAE under general anesthesia, and all were sacrificed for pathological examination 1 week after ozone administration. Their cochleas were removed. The outer hair cell damage and stria vascularis damage were examined. In the statistical analysis conducted, a statistically significant difference between Group 1 and Group 2 was observed in all frequencies according to the DPOAE test. In addition, between Group 2 and Group 3, a statistically significant difference was observed in the DPOAE test. However, a statistically significant difference was not observed between Group 1 and Group 3 according to the DPOAE test. According to histopathological scoring, the outer hair cell damage score was statistically significantly high in Group 2 compared with Group 1. In addition, the outer hair cell damage score was also statistically significantly high in Group 2 compared with Group 3. Outer hair cell damage scores were low in Group 1 and Group 3, but there was no statistically significant difference between these groups. There was no statistically significant difference between the groups in terms of stria vascularis damage score examinations. Systemic ozone gas therapy is effective in the treatment of cell damage in cisplatin-induced ototoxicity. The intratympanic administration of ozone gas does not have any additional advantage over the rectal administration.

Luteolin ameliorates colistin-induced nephrotoxicity in the rat models.

INTRODUCTION AND AIM: To study the protective, preventive effect of luteolin from colistin-induced nephrotoxicity. MATERIAL AND METHOD: Four different treatment options were tested on rats: colistin, luteolin, and a combination of colistin and luteolin, intraperitoneally as two doses a day, for seven days. Another group of rats were used as the control and treated with sterile saline. Serum creatinine levels were measured before and after treatment. Histological changes and colistin-induced apoptosis (Insitu BrdU-red DNA Fragmentation Assay Kit) of the renal tissues were examined after the scarification procedure. RESULTS: In the Colistin Group, post-treatment creatinine levels were statistically higher than the pretreatment levels (p = .001). In the remaining groups, no significant changes were observed. Cells that undergo apoptosis were counted and it was shown that all groups except the colistin-treated group had a similar number of apoptotic cells, whereas the colistin-treated group had statistically higher number of apoptotic cells compared to other groups (p = .0001). Renal histological damage was also measured and the score of the colistin treated group was higher as compared to other groups. CONCLUSION: The results obtained from this study demonstrated us that luteolin was capable of preventing colistin-induced nephrotoxicity and that this effect was significant at histopathological level.

Primary squamous cell carcinoma of the stomach.

Primary squamous cell carcinoma of the stomach accounts for less than 1% of all gastric malignancies. Less than 100 cases were reported in the literature. Therefore, knowledge about management and prognosis of the disease is limited. Surgical approach is the basic form of treatment. In this study we confirmed a case of primary gastric squamous cell carcinoma with the aim of contribution to the literature, which is seen rare, and the diagnosis was confirmed pathologically.

Metastatic follicular thyroid carcinoma masquerading as olfactory neuroblastoma: with skull-base, cranium, paranasal sinus, lung, and diffuse bone metastases.

Skull-base metastasis is rarely reported in thyroid carcinoma. We are presenting an unusual interesting case mimicking metastatic renal cell carcinoma with intense clear cell morphology, the thyroid origin of which was detected via positron emission tomography/computerized tomography scan proposed by the oncology council, while we were monitoring the subject with the initial diagnosis of paranasal sinus tumor. A mass was detected in the left nasal cavity in the endoscopic examination of the 68-year-old female patient referred by the ophthalmology clinic with the preliminary diagnosis of retro-orbital tumor upon being admitted with proptosis. A soft tissue lesion at a size of 68 × 39 × 53 mm located intracranially was detected by the brain computerized tomography. The biopsy taken and the immunohistochemical results were not satisfactory. Intense fluorodeoxyglucose involvement was observed in both lobes of the thyroid gland at positron emission tomography/computerized tomography taken with the recommendation of the council. Moreover, hypermetabolic nodules were seen in both lung parenchyma areas, whereas intense hypermetabolic lytic lesions were observed in the skeletal system. Thyroglobulin and thyroid transcription factor 1 stains displayed a strong staining on paraffin block. On the basis of these characteristics, the case was regarded as compatible metastatic follicular thyroid carcinoma, with skull-base, cranial, retro-orbital, paranasal sinus, lung, and bone metastases. This case showed us that multidisciplinary work and assessment of the oncology council play a highly critical role in making the diagnosis and guiding the treatment.

Relative proportions of stromal to cellular components of pleomorphic adenomas: determination with shear wave elastography.

OBJECTIVES: The purpose of this study was to evaluate whether the relative proportions of stromal to cellular components of pleomorphic adenomas have an effect on the shear elastic modulus determined by shear wave elastography (SWE). METHODS: This study was approved by the Ethics Committee of our institution and performed between September 2011 and December 2012. Thirty-five patients who underwent surgery for a parotid mass were included in the study. The maximum shear elastic modulus of the mass was measured by SWE. Pleomorphic adenomas were histopathologically subdivided into stroma-poor, intermediate-stroma, and stroma-rich tumors based on the relative proportion of stromal to cellular components. RESULTS: The maximum shear elastic modulus values of the pleomorphic adenomas ranged from 12.6 to 291.9 kPa (mean ± SD, 120.9 ± 92.8 kPa). The Friedman test revealed a statistically significant relationship between the stromal amount and maximum shear elastic modulus (P < .001). Stroma-poor adenomas (mean, 32.3 ± 27.7 kPa; range, 12.6-81.1 kPa) were softer on SWE than stroma-rich adenomas (mean, 174.1 ± 48.4 kPa; range, 92.7-217.2 kPa; P = .009). No such significant difference was detected between stroma-poor and intermediate-stroma tumors (mean, 146.3 ± 106.1 kPa; range, 19.1-291.9 kPa; P = .062) or between intermediate-stroma and stroma-rich tumors (P = .465). CONCLUSIONS: Shear wave elastography depicts pleomorphic adenomas with a variable appearance, which is due to the relative proportions of stromal to cellular contents in the tumors.

Gastrointestinal autonomic nerve tumour of jejunum presenting as a perforated mass.

Gastrointestinal autonomic nerve tumour (GANT) is a rare mesenchymal neoplasm of the gastrointestinal tract arising from the neural plexus of the intestinal wall. Herein, we present a 70-year-old male patient presenting with a clinical picture of acute abdomen. Examination of the specimen obtained from the small bowel by means of complete resection revealed a relatively soft submucosal mass measuring 4.5 x 3 cm in size with spindle morphology and high mitotic activity (> 10 mitoses per 50 high-power fields). The tumour cells were strong positive for c-kit (CD117), S-100 protein and glial fibrillary acidic protein (GFAP), but did not harbour mutations in the c-kit and PDGFR genes. The diagnosis was based on light microscopy and immunohistochemical verification. We started tyrosine kinase inhibitor 400 mg/day. The patient is currently alive without metastasis at 28 months postoperatively. He is under close follow-up and survival data of the patient will be presented in the later studies.

Comparison between 18F-FDG PET/CT and diffusion-weighted imaging in detection of invasive ductal breast carcinoma.

Objectives: Breast carcinoma is the most common type of cancer in females. This study aims to compare fluorine-18-fluorodeoxyglucose (18F-FDG) uptake pattern and apparent diffusion coefficient (ADC) value for the detection of the primary tumour and axillary metastases of invasive ductal breast carcinoma. Methods: This study included 40 breast carcinoma lesions taken from 39 patients. After staging by positron emission tomography-computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (MRI), breast surgery with axillary lymph node dissection or sentinel lymph node biopsy was performed. Results: Primary lesion detection rate for PET/CT and diffusion-weighted MRI was high with 39 of 40 lesions (97.5%). The sensitivity and specificity for the detection of metastatic lymph nodes in axilla were 40.9%, 88.9%, with 18F-FDG PET/CT scans and 40.9%, 83.3%, for dw-MRI, respectively. No significant correlation was detected between ADC and SUVmax or SUVmax ratios. Estrogen receptor (p=0.007) and progesterone receptor (p=0.036) positive patients had lower ADC values. Tumour SUVmax was lower in T1 than T2 tumour size (p=0.027) and progesterone receptor-positive patients (p=0.029). Tumour/background SUVmax was lower in progesterone receptor-positive patients (p=0.004). Tumour/liver SUVmax was higher in grade III patients (p=0.035) and progesterone receptor negative status (p=0.043). Conclusions: This study confirmed the high detection rate of breast carcinoma in both modalities. They have same sensitivity for the detection of axillary lymph node metastases, whereas the PET/CT scan had higher specificity. Furthermore, ADC, SUVmax and SUVmax ratios showed some statistical significance among the patient groups according to different pathological parameters.

Relapsing idiopathic scrotal calcinosis.

Idiopathic scrotal calcinosis is a rare and benign disease of the scrotum which is described in all age groups. It was initially first defined by Lewinski in 1883. Although many mechanisms have been proposed in the pathogenesis, underlying mechanisms are still controversial at the present time. Currently, the best therapeutic approach is the surgical removal of the scrotum without disrupting its integrity. Although it is indicated in literature that its recurrence is still controversial, we have observed relapse two times in our 41 year-old male patient following surgery at the 19th and 33rd months. We have confirmed recurrence with clinical and pathological assessments. Idiopathic scrotal calcinosis may recur both clinically and pathologically in the long-term follow up. Recurrence should be confirmed with post-surgical long-term follow up in larger series.

Pralatrexate for Peripheral T-Cell Lymphoma (PTCL): Chance Only Supports The Prepared Mind.

BACKGROUND: Due to their primary effects on DNA synthesis, antimetabolites are most effective against actively dividing cells and are significantly specific to the cell cycle phase. Pralatrexate (PDX), an antifolate metabolite designed to accumulate in cancer cells, was the first new agent approved by the US Food and Drug Administration for the treatment of resistant/recurrent peripheral T-cell lymphomas. PDX was a drug that is frequently used not only for PTCL, but also for cutaneous T-cell lymphoma (CTCL), extranodal natural killer (NK) / T-cell lymphoma. OBJECTIVE: This article reviews Pralatrexate's history, pharmacokinetics, clinical phase studies including phases I, II and III, types of cancers it is effective on, drug side effects, inhibition mechanism and even its use in the treatment of other cancers with innovative methods, including its antiviral effect against SARS-CoV-2 infection. METHODS: A comprehensive internet-based research was planned, covering all published and unpublished studies on the subject. We conducted this review in accordance with Preferred Reporting Items for systematic reviews and metaanalysis (PRISMA-P), and Cochrane Collaboration reporting items for systematic reviews and meta-analysis. The results of the studies in the articles were recorded to include all phase studies. RESULTS: Pralatrexate was structurally designed to have enhanced cellular transport via RFC (reduced folate carrier type) and be subject to more polyglutamation compared to methotrexate. The enhanced polyglutamylation ability of pralatrexate is associated with increased tumor cell death and ultimately improved anticancer activity. Pralatrexate is considered a promising drug for patients with recurrent and treatment-resistant PTCL with a good survival advantage. At the same time, it is an antifolate agent with a significant advantage over methotrexate as it does not cause myelosuppression. CONCLUSION: While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.

Unexpectedly High Coexistence Rate of In Situ/Invasive Carcinoma In Phyllodes Tumors. 10-Year Retrospective and Review Study.

Objective: Phyllodes tumors (PTs) are a rare group of breast tumors. Most malignant transformations are in situ carcinomas that are extremely rare and are limited to individual cases in the literature. The presence of in situ/invasive carcinomas is important as this may alter clinical judgment and management. In this study, we aimed to determine the association of in situ/invasive carcinomas among PTs. Materials and Methods: This retrospectively designed study included cases diagnosed with PTs between 2011 and 2020 in the pathology department of a tertiary level hospital. Tumors were grouped into benign, borderline and malignant, according to stromal overgrowth, stromal atypia, stromal cellularity and mitotic activity. In addition, age, location, type of operation, tumor diameter, and surgical margin information were recorded. in situ and/or invasive carcinoma foci accompanying the PTs were assessed. Results: A total of 29 patients diagnosed with PTs were identified, among whom 14 (48.2%) had benign PTs, 10 (34.4%) had borderline PTs, and 5 (17.2%) had malignant PTs. Of the patients with PTs, 3 (10.3%) had coexistent invasive carcinoma and 1 (3.4%) had carcinoma in situ. In this cohort the incidence of coexistence of PT and carcinoma was 4/29 (13.7%), which is much higher than previously reported (1.1% and 6%). The incidence of carcinoma was 2/5 (40%) in malignant PT patients and 2/10 (20%) in borderline PT patients. The coexistence of malignant PTs and carcinoma was significantly higher than those of benign and borderline PTs (p<0.05). Conclusion: The multidisciplinary team dealing with breast diseases has a great responsibility in both diagnosis and treatment. We anticipate that these rates will increase with an increase in the awareness and importance of this coexistence of carcinoma and PTs.