Benefit of adjuvant chemotherapy in patients with special histology subtypes of triple-negative breast cancer: a systematic review.

PURPOSE: Breast cancer (BC) is a leading cause of morbidity, disability, and mortality in women, worldwide; triple-negative BC (TNBC) is a subtype traditionally associated with poorer prognosis. TNBC special histology subtypes present distinct clinical and molecular features and sensitivity to antineoplastic treatments. However, no consensus has been defined on the best adjuvant therapy. The aim of the review is to study the evidence from literature to inform the choice of adjuvant treatments in this setting. METHODS: We systematically searched literature assessing the benefit of adjuvant chemotherapy in patients with TNBC special histotypes (PROSPERO: CRD42020153818). RESULTS: We screened 6404 records (15 included). All the studies estimated the benefit of different chemotherapy regimens, in retrospective cohorts (median size: 69 patients (range min-max: 17-5142); median follow-up: 51 months (range: 21-268); mostly in Europe and USA). In patients with early-stage adenoid cystic TNBC, a marginal role of chemotherapy was reported. Similar for apocrine TNBC. Medullary tumors exhibited an intrinsic good prognosis with a limited role of chemotherapy, suggested to be modulated by the presence of tumor-infiltrating lymphocytes. A significant impact of chemotherapy on the overall survival was estimated in patients with metaplastic TNBC. Limitations were related to the retrospective design of all the studies and heterogeneous treatments received by the patients. CONCLUSIONS: There is potential opportunity to consider treatment de-escalation and less intense therapies in some patients with early, special histology-type TNBC. International efforts are indispensable to validate prospective clinical decision models.

Unexpected Mycoplasma hominis infection in two renal transplant recipients traced back to the same donor by whole-genome sequencing.

Mycoplasma hominis is a common colonizer of the lower genitourinary tract. Although its clinical relevance for causing urogenital infections in immunocompetent individuals is controversial, this bacterium has been involved in severe invasive infections in allograft recipients. In this report, we describe two cases of M. hominis infection in two young renal transplant recipients within the first month post-transplant. Although at first no epidemiological link between the two cases had been suspected, whole-genome sequencing (WGS) analysis showed that both isolates were identical, highly suggestive of an origin with the common organ donor.

Effects of weak/non-complement-binding HLA antibodies on C1q-binding.

It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding. C1q-binding occurred only after a critical amount of IgG1/3 has bound and sharply increased thereafter. When both, C-binding and weak/non-C-binding IgG subclasses were mixed, C1q-binding was diminished proportionally to the fraction of IgG2/4. A 2- to 4-fold excess of IgG2/4 inhibited C1q-binding by 50%. Very high levels (10-fold excess) almost completely abrogated C1q-binding even in the presence of significant IgG1/3 levels that would usually lead to strong C1q-binding. In sensitized renal allograft recipients, IgG subclass constellations with ≥ 2-fold excess of IgG2/4 over IgG1/3 were present in 23/66 patients (34.8%) and overall revealed slightly decreased C1q signals. However, spiking of patient sera with IgG2 targeting a different epitope than the patient's IgG1/3 synergistically increased C1q-binding. In conclusion, if targeting the same epitope, an excess of IgG2/4 is repressing the extent of IgG1/3 triggered C1q-binding in vitro. Such IgG subclass constellations are present in about a third of sensitized patients and their net effect on C1q-binding is slightly inhibitory.

Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients.

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

Orthofile®: a new approach for mechanical interproximal reduction : a scanning electron microscopic enamel evaluation.

PURPOSE: The aim of this in vitro study was to evaluate the stripping achieved on different teeth (incisors, canines, and premolars) by two grades of abrasive strips used for the first and tenth time. Our second aim was to test the efficacy of these strips by calculating the time necessary to perform interproximal reductions of 0.10, 0.20, and 0.30 mm. METHODS: Four models were constructed using extracted teeth affixed in wax. The upper and lower arches were set on plaster bases and fixed in wax, carefully creating contact points. All model mouths were treated with artificial saliva (Oral Balance®) in order to simulate the biological conditions in the oral cavity. We then tested specific air-rotor strips of different grades and degrees of wear (15-µm-grain and 25-µm-grain Orthofile® strips). Afterwards the teeth from all samples were cut lengthwise in half, and each mesial and distal portion was gold-plated and observed under SEM at incremental magnification (30, 60, and 100 µm). RESULTS: The 25-µm-grain strip was more effective than the 15-µm-grain strip, irrespective of the tooth involved. Second, the finishing phase with specific polishing strips after interproximal reduction was fundamental in reducing the number of abrasions and irregularities created by stripping, in particular after using the 25-µm-grain strip. To achieve the best result, the entire abraded area must be polished. CONCLUSION: This system permits a rapid and effective stripping procedure in direct proportion to the strip's grain and in inverse proportion to the wear from its use. Further research will enable us to compare this system with similar procedures.

MRI of the small-bowel: how to differentiate primary neoplasms and mimickers.

MRI of the gastrointestinal tract is gaining clinical acceptance and is increasingly used to evaluate patients with suspected small-bowel diseases. MRI may be performed with enterography or enteroclysis, both of which combine the advantages of cross-sectional imaging with those of conventional enteroclysis. In this paper, MRI features of primary small-bowel neoplasms, the most important signs for differential diagnosis and the diseases that can be considered as mimickers of small-bowel neoplasms, are discussed.

Detection of clinical and subclinical tubulo-interstitial inflammation by the urinary CXCL10 chemokine in a real-life setting.

Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

Lipoblast-like signet-ring cells in neurofibroma: a potential diagnostic pitfall of malignancy.

Benign peripheral nerve sheath tumours, including neurofibroma, may occasionally contain a heterologous mature fatty component. Additional lipoblast-like cells can be occasionally identified among mature adipocytes. We report the first case of a plexiform neurofibroma from a NF1 patient containing exclusively lipoblast-like cells exhibiting morphological and immunohistochemical features identical to univaculoted lipoblasts typically seen in myxoid liposarcoma. Awareness of the possibility that an otherwise typical neurofibroma may contain lipoblast-like cells is crucial for the pathologist to avoid a misdiagnosis of malignancy. Differential diagnostic problems and histogenetic considerations are provided.

Atypical dermatofibroma with predominant epithelioid/deciduoid-like cell component. Histogenetic considerations in the wide spectrum of fibrohistiocytic dermal tumours.

Atypical and epithelioid cell variants of dermatofibroma may represent a potential diagnostic pitfall. Only rarely atypical dermatofibroma may show focal epithelioid cell features. We herein report a rare case of dermatofibroma composed of a predominant (> 90%) epithelioid/deciduoid-like cell component, in which rare multinucleated bizarre cells and atypical mitoses were additional findings. Tumour was classified as "atypical dermatofibroma with predominant epithelioid/deciduoid-like cell component". The coexistence of at least two different variants, i.e. epithelioid and atypical variants, in the same dermatofibroma suggests that dermal fibrohistiocytic tumours belong to a continuous morphological spectrum. Accordingly, the morphological variants of dermatofibroma should be regarded as variations on a common basic theme. Differential diagnosis with other epitheliod cell dermal tumour- and tumour-like lesions is discussed.

Efficacy of induction therapy with ATG and intravenous immunoglobulins in patients with low-level donor-specific HLA-antibodies.

Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

Diffuse and extreme vacuolization of tumour cells in rectal adenocarcinoma after neoadjuvant therapy: an unusual finding.

We report a case of diffuse and extreme cytoplasmic vacuolization of tumour cells in a rectal adenocarcinoma after neoadjuvant treatment. A 64-year-old man with a moderately differentiated rectal adenocarcinoma, diagnosed by endoscopic rectal biopsy, underwent surgical treatment after chemoradiotherapy. Residual tumour mass was represented by foci of neoplastic cells with the morphological features of conventional type adenocarcinoma, and surprisingly, by numerous areas consisting of several giant vacuoles, variable in size, merging to form multilocular spaces separated by a rim of cell membrane with a "plant-like" appearance. Cytoplasmic vacuolization may represent a distinct form of cell death, and pathologists should carefully consider this unusual and potentially alarming morphological change among the chemoradiotherapy-induced effects on tumour mass.

Fibrous hamartoma of infancy of the labium majus: a typical lesion in an unusual site.

Fibrous hamartoma of infancy is a soft tissue subdermal fibromatous tumour that characteristically occurs in the first years of life. It is histologically composed of three different components that are intimately admixed: well-defined bundles of fibro-myofibroblastic spindle-shaped cells, nodular proliferations of immature-looking mesenchymal cells set in a myxoid stroma, and mature adipose tissue. A wide intralesional and interlesional cellular composition is commonly observed. Fibrous hamartoma of infancy usually arises from subcutaneous tissue of the trunk, axilla, upper extremities and inguinal region. Only rarely has fibrous hamartoma of infancy been reported in genital organs, with only one case described in the labium majus. We report a rare case of fibrous hamartoma of infancy in the labium majus of a 1-year old female child. Ultrasonography revealed the presence of a mass-like lesion involving subcutaneous tissue, with ill-defined margins. We emphasize that fibrous hamartoma of infancy should be included in the differential diagnosis of soft tissue tumour-like and tumour lesions of the vulva in children. Awareness that fibrous hamartoma of infancy occurs at this site with irregular margins is important to avoid confusion with other lesions exhibiting a more aggressive behaviour.

Aliskiren corrects recurrent hyperreninemia and hyperaldosteronism in autosomal dominant polycystic kidney disease.

A 47-year-old woman with family history of autosomal-dominant polycystic kidney disease (ADPKD), who underwent living-donor kidney transplantation in 2000, presented with recurrent edema, hyperreninemia, and hyperaldosteronism. Since 2002, her antihypertensive therapy comprised ramipril and spironolactone. The post-transplantation kidney function was stable. Based on the clinical picture and reports of renin secretion by renal cysts in ADPKD, we performed a trial of aliskiren therapy (300 mg/day). The patient showed excellent blood pressure control and reduction of edema, with aldosterone levels normalizing within 2 months. This is a novel report of aliskiren therapy for treatment of edema, hyperreninemia, and hyperaldosteronism in ADPKD.

[Mammary hamartoma with atypical stromal cells: a potential diagnostic dilemma]. / Amartoma mammario con cellule stromali atipiche: un potenziale allarme diagnostico per il patologo.

Hamartoma of the breast is a pseudotumoural lesion that does not usually pose diagnostic problems for the pathologist. Although atypical stromal cell (ASCs) can be encountered in several benign and malignant breast lesions, their occurrence in hamartoma has not been reported to date. The authors report a case of breast hamartoma containing numerous atypical mono- or multinucleated stromal cells within the fibro-fatty component. This unusual feature raised differential diagnostic problems with pleomorphic lipoma, well-differentiated liposarcoma and malignant phylloid tumour with a lipomatous heterologous component. Immunohistochemistry, showing positivity to vimentin and CD34, revealed that ASCs are fibroblastic in nature, and thus are likely to represent a morphological variant of the fibroblasts of the native mammary stroma.

[Carcinoma of the Bellini collecting duct in paediatric patients: a case report and review of the literature]. / Carcinoma dei dotti collettori di Bellini in età pediatrica: descrizione di un caso e revisione della letteratura.

Collecting duct carcinoma is an uncommon variant of renal cell carcinoma that usually occurs at an earlier age compared to conventional renal cell carcinoma. It is characterised by an aggressive, often fatal, course. Renal cell carcinoma rarely occurs in paediatric patients, and is almost always in association with specific genetic alterations; the most common histotypes are the clear cell and chromophobe cell variants. Collecting duct carcinoma is rare, and only 8 cases have been reported in the literature. The authors describe the clinico-pathological features of a fatal collecting duct carcinoma in an 11-year-old boy.

Patient-oriented assessment of back pain in pregnancy.

Back pain is a common symptom in women during the last period of pregnancy. Only a few studies using validated patient-oriented tools have been undertaken on this topic. We report on a multicenter study on back pain in women during the last period of pregnancy, which involved seven Italian institutions. Seventy-six women in their 8th and 9th months were studied using the Italian validated version of the Roland questionnaire -- a disease-specific patient-oriented tool for low back pain. Sixty-two percent of the women had gone through at least one previous pregnancy, and clinical data concerning both the period before all pregnancies and the period before the current pregnancy were acquired. The study found that 31% of the women had no back pain symptoms (Roland score 0), 40% scored from 1 to 4, 21% scored from 5 to 10, and 8% scored more than 10. With regard to the predictive factor, history of back pain and sciatica before the pregnancy were found to be associated with occurrence of back pain symptoms during pregnancy. Unexpectedly, our results showed that male sex of the fetus seems to be related to occurrence of back pain symptoms during pregnancy. However, back pain was not associated with having gone through previous pregnancies, nor was the Roland score related to the weight before pregnancy or to increment of weight during pregnancy. Evaluation of the patient's perspective made it possible to identify predictive factors for occurrence of back pain, thereby furnishing important information for the clinical approach to pregnancy.

A new clinical scale of carpal tunnel syndrome: validation of the measurement and clinical-neurophysiological assessment.

OBJECTIVE: To validate a new clinical scale of carpal tunnel syndrome (CTS). The scale is based on clinical history and physical examination findings and includes two figures. The first is a score determined by clinical history and objective findings. The second evaluates the presence/absence of pain as a dichotomous categorical score. METHODS: One hundred and sixty-eight consecutive idiopathic CTS hands were studied in two centers (Rome, Siena). We compare the results of the historical-objective scale (Hi-Ob scale) with the results of other validated measurements of CTS severity: (1) the Italian version of the Boston Carpal Tunnel Questionnaire, (2) the neurophysiological classification adopted by the Italian CTS study group. Furthermore, for the Hi-Ob scale the intra-observer and inter-observer evaluations were assessed. RESULTS: The main Hi-Ob parameter was positively related to the conventional validated measurements. Conversely, the category 'PAIN' of the Hi-Ob scale appeared unrelated to the other clinical and electrophysiological parameters. Intra- and inter-observer evaluation showed the reproducibility of the Hi-Ob assessment. CONCLUSIONS: Our data show that the Hi-Ob scale is a reliable measurement which may be useful in CTS evaluation either for clinical or for scientific purposes.