Clinical relevance of gene mutations and rearrangements in advanced differentiated thyroid cancer.

BACKGROUND: Tumor genotyping is becoming crucial to optimize the clinical management of patients with advanced differentiated thyroid cancer (DTC); however, its implementation in clinical practice remains undefined. We herein report our single-center experience on molecular advanced DTC testing by next-generation sequencing approach, to better define how and when tumor genotyping can assist clinical decision making. MATERIALS AND METHODS: We retrospectively collected data on all adult patients with advanced DTC who received molecular profiling at the IRCSS Sant'Orsola-Malpighi Hospital from 2008 to 2022. The genetic alterations were correlated with radioactive iodide refractory (RAI-R), RAI uptake/disease status, and time to RAI resistance (TTRR) development. RESULTS: A significant correlation was found between RAI-R development and genetic alterations (P = 0.0001). About 48.7% of RAI-R cases were positive for TERT/TP53 mutations (as both a single event and comutations with other driver gene alterations, such as BRAF mutations, RAS mutations, or gene fusions), while the great majority of RAI-sensitive cases carried gene fusions (41.9%) or were wild type (WT; 41.9%). RAI uptake/disease status and time to TTRR were significantly associated with genetic alterations (P = 0.0001). In particular, DTC with TERT/TP53 mutations as a single event or as comutations displayed a shorter median TTRR of 35.4 months (range 15.0-55.8 months), in comparison to the other molecular subgroups. TERT/TP53 mutations as a single event or as comutations remained independently associated with RAI-R after Cox multivariate analysis (hazard ratio 4.14, 95% CI 1.51-11.32; P = 0.006). CONCLUSIONS: Routine testing for genetic alterations should be included as part of the clinical workup, for identifying both the subset of more aggressive tumors and the subset of tumors harboring actionable gene fusions, thus ensuring the appropriate management for all patients with advanced DTC.

Adenocarcinoma classification: patterns and prognosis.

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications.

Diffuse parenchymal lung diseases: when you see, think!

In this article, a series of tables (presented in alphabetic order) summarize the differential diagnosis of diffuse parenchymal lung diseases starting from the most frequent elementary lesions.

Long-term efficacy of botulinum toxin A for treatment of blepharospasm, hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes.

PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation.

[Thyroid maltoma: report of a case without coexistent Hashimoto's thyroiditis]. / Maltoma della tiroide: presentazione di un caso non associato a tiroidite di Hashimoto.

Maltomas of the thyroid are rare neoplasms that originate from parafollicular B lymphocytes and are often associated with autoimmune thyroiditis (Hashimoto's disease). The authors describe a case of a primary thyroid lymphoma in which no evidence for a previous thyroiditis could be found during clinical evaluation (clinical progression of the tumor, diagnostic studies, preoperative cytology, histology of the surgical specimen). Noteworthy was the development of a severe form of pure red cell aplasia (PRCA) about 6 months after the operation without detectable autoantibodies or signs of previous viral infection. The aplasia resolved completely with corticosteroid therapy.

[The tension-free hernioplasty for primary inguinal hernias: personal experience]. / Il trattamento dell'ernia inguinale con tecnica "tension free". Esperienza personale.

The Authors report their experience in the treatment of primary inguinal hernias using Trabucco's tension-free technique. Since April 1998 to June 2002 four hundred and fifteen patients (399 men and 16 women) were treated in our Department for primary inguinal hernia. The results demonstrate the efficacy of this technique in reducing post-operative complications and in preventing relapses. The reduction of costs is related to a shorter hospitalization and an earlier return to work.

Abrikossoff's tumour: report of a rare case in anal perianal region.

The authors report a rare case of a 47-year old man suffered from Crohn's disease and depression with multiple prominent lesions in the anal and perianal region. The biopsy of these lesions showed the presence of Abrikossoff's tumour. This tumour is very rare in the anal region and usually the lesions are small (0.5-3 cm) and solitary. The authors report this case because they considered it an interesting case for the localization and the appearance of the lesions.

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.

Five cases of a hitherto undescribed breast tumor having histologic features similar to those of the tall cell variant papillary thyroid carcinoma are described. They were composed of columnar mitochondrion-rich to oxyphilic cells arranged in nests, papillae, and follicle-like structures. In addition, the neoplastic cells showed numerous nuclear grooves and, in two cases, nuclear pseudo-inclusions. None of the patients had previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further excluded a metastasis from the thyroid in the four cases tested, as they were consistently thyroglobulin and thyroid transcription factor 1 negative.

Smooth muscle cell differentiation in mammary stromo-epithelial lesions with evidence of a dual origin: stromal myofibroblasts and myoepithelial cells.

AIMS: We investigated the origin of myoid cells in benign stromo-epithelial lesions of the breast in order to ascertain their myoepithelial or myofibroblastic origin. METHODS AND RESULTS: We selected 22 stromo-epithelial lesions of the breast and reviewed their morphological features at haematoxylin-eosin (H&E) level. The lesions were classified as fibrous stromo-epithelial lesions (without evidence of myoid differentiation at H&E level) (13 cases), type 1 myoid stromo-epithelial lesions (myoid cells directly merging with the myoepithelial layer) (three cases), type 2 myoid stromo-epithelial lesions (bundles of myoid cells unrelated to the glands) (six cases). All cases were studied immunohistochemically and myoid stromo-epithelial lesions were also studied with electron microscopy. The myoid component in two out of three cases of type 1 myoid lesions showed immunohistochemically co-expression of smooth muscle and myoepithelial markers. In contrast, the remainder showed immunohistochemical results identical to those found in type 2 myoid lesions (positivity with SMA, desmin, calponin, CD34 and bcl2 and negativity with cytokeratin 14 and p63). Ultrastructural study confirmed the presence of cells with myoepithelial features in type 1 myoid lesions and of cells with myofibroblastic features in type 2 myoid lesions. CONCLUSIONS: Myoid cell differentiation is common in stromo-epithelial lesions of the breast, and is evident in H&E sections in up to 40% of cases. In addition, the origin of myoid cells is myofibroblastic in most cases, but in some cases, cells present immunohistochemical and ultrastructural evidence of myoepithelial origin.

[Surgical treatment of esophageal achalasia. Personal trend]. / Il trattamento chirurgico dell'acalasia esofagea. Nostro orientamento.

AIM: Achalasia of the esophagus involves the entire esophagus from the upper esophageal sphincter (UES) to the lower esophageal sphincter (LES) together with a wide spectrum of physiopathological and clinical variations. Therefore, the need to know exactly the different involvement either of the body of the esophagus or the LES for each case is underlined. In our experience, the cineradiology is the only technique that allows a complete morphologic and functional study of the disease. It is through cinesophagography that we can exactly establish the extension of myotomy according to the physiopathological aspects that will suggest the most accurate surgical treatment. It is our opinion to perform a short myotomy, to the gastroesophageal junction, through an abdominal approach in grade II and III achalasia, when the most important physiopathological aspects involve only the LES area (hypertonic LES or dischalasia). We extend the myotomy from the LES up to the aortic arch through a thoracic approach. METHODS: From 1984 to 2002, we have treated 148 achalasic patients, 90 through an abdominal approach, 22 by VALS (Video Assisted Laparoscopic Surgery) and 36 through a thoracic approach. In the first 2 groups we performed a short myotomy with a Dor antireflux procedure, in the 3rd group we performed a long myotomy with a Belsey Mark IV antireflux procedure. RESULTS: Our trend to calibrate the surgical treatment on the physiopathological and morphofunctional data, allowed to optimize the post-operative clinical results, particularly with a better control of dysphagia. CONCLUSIONS: Surgical treatment of achalasia must be differentiated according to the pathophysiological basis in order to improve the surgical results.

[Gastrointestinal stromal tumors: clinical considerations]. / Considerazioni cliniche sui tumori gastrointestinali stromali.

Gastrointestinal stromal tumors (61ST) are an heterogeneous group of non epithelial tumors of the gastrointestinal tract. They are peculiar to extreme cellular variability and uncertain malignancy. Gist are rare tumors that arise from primitive mesenchymal cells located in all gastrointestinal tract. Till now they are object of discussion about their origin, diagnostic standards, prognostic factors, histopathological classification. They are more frequently in over 40 years old people without difference in two sex, but they can appear in the child too and in the young man suffering from HIV. The authors relate two cases of recent observation, and discuss on the biological behaviour of these rare tumors.

[Pilonidal sinus: an retrospective analysis of 205 cases]. / Sinus Pilonidale. Analisi retrospettiva di 205 casi. Metodo chiuso versus metodo aperto.

Sinus pilonidalis or the sacrococcigea cyst, normally is considered a "small surgical pathology" and actually it is controversial disease regarding its pathogenesis and treatment. Today the congenital hypothesis of this pathology is not considered. The etiopathogenesis exclude vestigia embryonic origin and consider it an inflammatory disease. Traumatism of the sacral region, hirsutism, hormonal secretion stimulating, and furrow sacral furrow cutaneous, explain the prevalence of this pathology in the male sex and in the puberale age. It usually appears after the pubertà and extension one various frequency of presentation in males sex (1.3%) regarding females (0.11%). The symptomatology can be rare or introduce itself in violent and intense way with on abscess of the region, or with only or multiple fistulas orifices from which exit materialclarly purulent. Normally cystic cavity is one, situated in the subcutaneous tissue with annexed inflammatory phenomena. This cavity to times communicates with the skyn fistulating. The treatment of election is surgical and must weighted and be regulated in relation to the entity of the lesion and its inflammatory picture. Sometimes the medical therapy with anti-inflammatory and antibiotic is not control the symptomatology and it need the surgical treatment.

Malignant neoplasms infiltrating pseudoangiomatous' stromal hyperplasia of the breast: an unrecognized pathway of tumour spread.

AIMS: To describe five malignant tumours in the breast (two invasive carcinomas and three non-Hodgkin's lymphomas) showing an unusual pattern of spread within anastomosing spaces consistent with those described in pseudoangiomatous stromal hyperplasia. METHODS AND RESULTS: The histological and immunohistochemical features of the cases are presented. In all cases, the neoplasms consisted of non-cohesive E-cadherin-negative cells located within anastomosing vascular-like channels. These channels showed morphological and immunohistochemical features consistent with those seen in pseudoangiomatous stromal hyperplasia: they were lined by flattened cells that expressed CD34, bcl2 and smooth muscle actin, while CD31 was consistently negative. CONCLUSIONS: The open channels of pseudoangiomatous stromal hyperplasia have been regarded as spaces due to loss of cohesiveness between stromal fibroblasts if not artefacts. The fact that neoplastic cells spread through these spaces suggests that the spaces are true open channels that may represent part of a complex network of stromal channels (pre-lymphatics) connected to the main lymphatic system of the breast. This finding opens new insights into the routes of tumour spread.