Granular cell tumor of the trachea mimicking an infiltrating thyroid cancer. A case report.

INTRODUCTION AND IMPORTANCE: Granular cell tumor (GCT) is a rare neurogenic neoplasm originating from Schwann cells that predominantly affects women and can involve skin and mucousae. In the respiratory system it most frequently involves bronchi and larynx, while it is rare in the trachea. CASE PRESENTATION: A 26-year old female smoker was hospitalized for a suspected hypoechoic nodule in the right thyroid lobe closely adherent to the trachea. At preoperative computed tomography tracheal lumen was totally clear. The patient underwent a total thyroidectomy with lymph node dissection and tracheal shaving. The postoperative course was complicated by an extensive subcutaneous bilatreral emphysema associated with respiratory distress appeared on the fifth day. Bronchoscopy revealed a right anterolateral subcentimeter lesion near the second tracheal ring. Histologically, the diagnosis was consistent with a tracheal GCT developing into the thyroid parenchyma. The patient was discharged on the twentieth postoperative day. At the follow-up bronchoscopy the lesion was completely healed and at the last 12 month follow-up the patient is doing well. CLINICAL DISCUSSION: Tracheal tumors are uncommon neoplasms accounting for about 2% of the total respiratory tree tumors. In literature we found <50 papers concerning tracheal GCT and in almost all of the cases patients complained about respiratory symptoms. CONCLUSION: We report here a rare case of benign GCT of the trachea with extraluminal development, in a young patient who did not complain about preoperative respiratory symptoms, presented on ultrasound as a thyroid nodule with suspected cytology.

Subcutaneous implantation of oncocytic thyroid cell aggregates nine years later from thyroidectomy. A case report.

INTRODUCTION AND IMPORTANCE: Subcutaneous implantation of thyroid tissue is a rare clinical condition that involves the head and neck region and occurs after surgery, diagnostic procedures or cervical trauma. CASE PRESENTATION: A 90-year old woman with two skin nodules on her thyroidectomy scar was hospitalized and treated by two surgical excisions. Histologically, these lesions were two aggregates of cutaneous oncocytic thyroid cells. In the patient's clinical history there was a total thyroidectomy for multinodular goiter, performed 9 years previously and at which a well-encapsulated subcapsular oncocytic adenoma of the left lobe was also incidentally discovered. At 12 months of follow-up, the patient is showed well and her wounds healed. CLINICAL DISCUSSION: Subcutaneous colonization or seeding of thyroid tissue is a rare occurrence reported in the literature for both benign and malignant pathologies; among the malignant ones, the implantation of follicular carcinoma cells is the most frequent. Only in one previous case, to our knowledge, subcutaneous colonization originating from oncocytic thyroid (or Hurthle) cell neoplasms has been described. CONCLUSION: We report an unusual case of double subcutaneous implantation of oncocytic thyroid cells on the cervical scar of an elderly woman, nine years after total thyroidectomy.

Larynx lymphoepithelial carcinoma: surgical management.

Lymphoepithelial carcinoma (LEC) is an entity mostly frequent in the nasopharynx, which represents 40% of all neoplasms. The incidence's not exclusive of a geographic area; however, it has an endemic distribution in Southeast Asia and Eskimos. LEC is not exclusive of the nasopharynx, has also been reported in other anatomical areas, such as the sinonasal tract, nasolacrimal duct, oral cavity, oropharynx, salivary glands, thymus, hypopharynx, oesophagus, stomach, trachea, lung and others. Non-nasopharyngeal and nasopharyngeal LEC have the same microscopic features, but the nasopharyngeal is more likely associated with Epstein-Barr virus. LEC has been approved by the WHO. LEC located in the larynx is quite rare and worthy of attention for its implication in the treatment and prognosis. We present a case of LEC treated in our ENT department in a middle-aged man.

Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor.

BACKGROUND: The effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated. AIM: To study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors. METHODS: 38 premenopausal women with type 1 diabetes aged 36 -46 years. A randomized 1:1 study design was used: Study Group (group A) on Tadalafil 5 mg daily, and control group (group B). Blood samples were taken from each woman to measure HbA1c, testosterone, and Free Androgen Index. The women underwent microbiopsy of the clitoral body by means of semiautomatic gun during total anesthesia for surgery therapy of a benign gynecological pathology. The tissue removed was processed for electron microscopy. Translabial color Doppler ultrasound was used to measure the peak systolic velocity (PSV), the end diastolic velocity (EDV), and the pulsatility index (PI) of clitoral arteries. MAIN OUTCOME MEASURES: Micro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow. RESULTS: Of the 38 women, 13 (68.4%) of group A and 15 (78.9%) of group B completed the study. Group A showed a mean PSV and EDV increase, and a mean PI decrease with respect to baseline (P < .001). Group B did not show any change in both the parameters (P = NS). By a quantitative study in both groups a variable degree of ultrastructural abnormalities of smooth muscle cells (SMCs) was observed, consisting in increased glycogen and lipoic deposits, cytoplasmic vacuoles, and focal increase of electron density of SMCs. Moreover, the mean SMC thickness of group A (1.83 ± 0.68 µm) was larger than that of group B (1.3 ± 0.41 µm) (P = .02). CLINICAL IMPLICATIONS: PDE5 inhibitors could be used to treat diabetic women with genital arousal disorder. STRENGTHS & LIMITATIONS: The study shows a clear effect of PDE5 inhibitors on clitoral SMCs. However, a limit was to not have investigated the sexual function/behavior of women of both groups, this was because of the short time of the study. CONCLUSION: This study could help to understand in what way PDE5 inhibitors act on the ultrastructural pathophysiological clitoral cavernous tissue of women with diabetes. It could support PDE5 inhibitor usage in women with genital sexual arousal disorder due to metabolic diseases. Caruso S, Cianci A, Cianci S, et al. Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor. J Sex Med 2019;16:375-382.

Coexistence of diffuse large B-cell lymphoma and papillary thyroid carcinoma in a patient affected by Hashimoto's thyroiditis

SUMMARY Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. On the contrary, primary thyroid lymphoma (PTL) is a rare disease, accounting for 2% to 5% of all thyroid malignancies. Despite several cases in which both PTC and PTL arise in the setting of Hashimoto's thyroiditis (HT), the coexistence of both tumors in HT patients is very rare. Herein we report the case of a 66-year-old woman with long-standing nodular HT under replacement therapy, who presented with a fast, painless enlargement in the right anterior side of the neck. Thyroid ultrasonography demonstrated increased growth of a hypoechoic nodule in the right lobe measuring 32 × 20 mm. A total thyroidectomy was performed, and histology revealed a diffuse large B-cell lymphoma (DLBCL) on a background of florid HT. Moreover, a unifocal papillary microcarcinoma, classical variant (7 mm, pT1aNxMx), was discovered. The patient was then treated with chemotherapy for the PTL, but she did not undergo radioactive iodine ablation treatment for the microPTC as per guidelines. Two years after surgery, the patient had no evidence of recurrence of either malignancy. This rare case highlights the importance of monitoring HT patients with nodular lesions, especially if they have long-standing disease. In addition, PTL should be considered for differential diagnosis in elder HT patients who present with sudden thyroid enlargement.

Coexistence of diffuse large B-cell lymphoma and papillary thyroid carcinoma in a patient affected by Hashimoto's thyroiditis.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. On the contrary, primary thyroid lymphoma (PTL) is a rare disease, accounting for 2% to 5% of all thyroid malignancies. Despite several cases in which both PTC and PTL arise in the setting of Hashimoto's thyroiditis (HT), the coexistence of both tumors in HT patients is very rare. Herein we report the case of a 66-year-old woman with long-standing nodular HT under replacement therapy, who presented with a fast, painless enlargement in the right anterior side of the neck. Thyroid ultrasonography demonstrated increased growth of a hypoechoic nodule in the right lobe measuring 32 × 20 mm. A total thyroidectomy was performed, and histology revealed a diffuse large B-cell lymphoma (DLBCL) on a background of florid HT. Moreover, a unifocal papillary microcarcinoma, classical variant (7 mm, pT1aNxMx), was discovered. The patient was then treated with chemotherapy for the PTL, but she did not undergo radioactive iodine ablation treatment for the microPTC as per guidelines. Two years after surgery, the patient had no evidence of recurrence of either malignancy. This rare case highlights the importance of monitoring HT patients with nodular lesions, especially if they have long-standing disease. In addition, PTL should be considered for differential diagnosis in elder HT patients who present with sudden thyroid enlargement.

Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules.

BACKGROUND: P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage. AIM: To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy. MATERIALS AND METHODS: By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto's thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro-follicular, 28 micro-follicular and 5 solid variants. RESULTS: Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG. CONCLUSION: The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes.

Sudden cardiac arrest in a child with nemaline myopathy.

BACKGROUND: Nemaline myopathy is a rare, non progressive congenital skeletal muscle disorder defined by the presence of inclusions known as nemaline rods in muscle fibers. Several clinical subtypes have been described, according to degree of muscle weakness, severity and age at onset. The course of nemaline myopathy is very slowly progressive, and death is usually due to respiratory failure. Cardiac involvement is rare and generally considered to be the result of ACTA1 mutations. PATIENT: We report the case of a 6 year old boy with typical congenital nemaline myopathy. Nemaline myopathy was confirmed at 3 years of age by muscle biopsy. No mutation of ACTA1, TPM2 and TNNT1 genes was detected. The child died suddenly of cardiac arrest and associated hypoxic-ischemic brain injury, in absence of acute respiratory failure or swallowing difficulties. RESULTS: Nemaline cardiomyopathy was suspected, but post mortem cardiac biopsy did not show findings consistent with nemaline myopathy. CONCLUSIONS: Congenital typical nemaline myopathy is not necessarily a static or very slowly progressive disorder and acute cardiac deterioration can lead to early death.

Drug-induced TINU syndrome and genetic characterization.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is due to a disregulation of cell-mediated immunity and genetical predisposition due a particular molecular characterization. We report the case of a 50-year-old woman who was admitted for acute renal failure. She had recently taken flurbiprofen for 10 d for recurrent bronchitis. A renal biopsy revealed acute tubulointerstitial nephritis. Prednisone was started and prognosis was favorable. Three months later the patient developed transitory blurred vision. The diagnosis was bilateral uveitis and she received topic and systemic corticosteroid therapy, with resolution of ocular symptoms. Recurrent episodes of uveitis experienced during the next 12 months were treated with same therapy. Genomic haplotype in our patients was HLA A*0278/2631,-B*1517/3802,- Cw*0701/1202, -DRB1*0101/1359 (DRB3* 52), -DQA1*0102/0102, DQB1*0603/0603. TINU syndrome is characterized by tubulointerstitial nephritis that tends to be selflimiting, whereas uveitis tends to relapse. HLA-DQA1*01 and -DQB1*06 haplotypes are strongly associated with TINU syndrome. This is the first report of TINU syndrome induced by flubiprofen intake. Our case emphasizes the importance of the association between drug exposure and strong susceptibility to TINU syndrome giving the molecular characterization.

Bioenergetics of T cell activation and death in HIV type 1 infection.

Regressive morphological lesions, found in peripheral lymphocytes from HIV(+) patients, clearly conflict with normal cycle progression and with the execution of basic housekeeping and immune functions. With these lesions, circulating lymphocytes are destined to spontaneous and energy-independent cell lysis. By means of confocal microscopy and morphometry, we have quantified the rate of circulating T cells that are probably destined to emocatheresis in vivo. This rate includes lymphocytes in which nucleolin fragments have been scattered out of the nuclear region as a result of prelethal alterations in the nuclear membrane permeability. In terms of bioenergetics, these cells show evident anomalies in the energy production machinery that make them unable to carry out ATP-requiring functions. The extent of damaged cell fraction in peripheral blood reflects the frequency with which T lymphocytes leave lymphoid tissue to be cleared in hemocatheretic processes.

Giant endobronchial hamartoma resected by fiberoptic bronchoscopy electrosurgical snaring.

Less than 1% of lung neoplasms are represented by benign tumors. Among these, hamartomas are the most common with an incidence between 0.025% and 0.32%. In relation to the localization, hamartomas are divided into intraparenchymal and endobronchial.Clinical manifestation of an endobronchial hamartoma (EH) results from tracheobronchial obstruction or bleeding. Usually, EH localizes in large diameter bronchus. Endoscopic removal is usually recommended. Bronchotomy or parenchimal resection through thoracotomy should be reserved only for cases where the hamatoma cannot be approached through endoscopy, or when irreversible lung functional impairment occurred after prolonged airflow obstruction. Generally, when endoscopic approach is used, this is through rigid bronchoscopy, laser photocoagulation or mechanical resection. Here we present a giant EH occasionally diagnosed and treated by fiberoptic bronchoscopy electrosurgical snaring.

Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects.

INTRODUCTION: There has never been an investigation about the in vivo clitoral structure. AIM: To study the "in vivo" age-related structural changes of the clitoris in healthy women and in those affected by metabolic disorders. METHODS: Forty-three women subgrouping in (i) five teenagers, aged 14-18; (ii) eight young premenopausal women, aged 23-32; (iii) 10 premenopausal women, aged 38-47; (iv) nine diabetic premenopausal women, aged 27-43; and (v) 11 naturally postmenopausal women aged 51-55. Each woman underwent microbiopsy of the clitoral body by means of an 18G needle, length 100 mm, using a semiautomatic gun during total anesthesia for a benign gynecological pathology. The tissue removed was processed for electron microscopy. A morphometric procedure was used on electron micrographs. MAIN OUTCOME MEASURE: Micro ultrastructure observation of clitoral tissue. RESULTS: The cavernous tissue from the teenagers and young women showed large amounts of smooth muscle cells (SMCs). The intercellular connective tissue showed scanty, small isometric collagen fibers and amorphous extracellular matrix. In the premenopausal diabetic women, ultrastructural abnormalities of SMCs were observed, consisting of increase of glycogen deposits, infolding cell borders, and cytoplasmic vacuoles. Moreover, the intercellular connective tissue was increased by densely packed collagen fibers. Finally, in the healthy, natural postmenopausal women, the SMCs were moderately reduced in number. We observed age-related structural changes of the vascular spaces and of the vascular lacunae. The SMC mean thickness was reduced with age; vascular abnormalities appeared to be correlated with the presence of metabolic diseases, such as diabetes. CONCLUSION: Our "in vivo" study could help to understand some aspects of the physiology of the clitoris and its role in sexual response. Apart from data obtained by studying healthy women and women affected by diabetes, other investigations are needed to study subgroups of otherwise healthy sexually dysfunctional women.

Abnormal nuclear structures (micronuclei, nuclear blebs, strings, and pockets) in a case of anaplastic giant cell carcinoma of the thyroid: an immunohistochemical and ultrastructural study.

The authors report a case of a 70-year-old woman with an anaplastic giant cell thyroid carcinoma, along with immunohistochemical and electron microscopic findings. Histologically, the tumor is characterized by mononucleated and multinucleated giant cells, lack of architectural cohesion, atypical mitoses, and extensive areas of coagulative necrosis. Tumor cells showed AE1/AE3 positivity as well as nuclear overexpression of p53 and ki-67. Semithin sections revealed multiple nuclei with heterogeneous size ranging from micronuclei to large-size (giant) nuclei. Micronuclei were confirmed by electron microscopy that disclosed also the presence of nuclear blebs, strings, and pockets. Morphological findings of these abnormal nuclear structures in conjunction with p53 and Ki-67 nuclear overexpression suggested a faulty mitotic checkpoint/mitotic catastrophe in the progression of anaplastic giant cell thyroid carcinoma.

The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause.

PURPOSE: The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA). METHODS: A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 µg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed. RESULTS: After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI. CONCLUSION: Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

Immunoprotective activities of a Streptococcus suis pilus subunit in murine models of infection.

Pili of gram-positive bacteria are key virulence factors and their subunits are considered excellent vaccine candidates. Streptococcus suis is an emerging zoonotic agent that can cause epidemics of life-threatening infections in humans, but the functional role or immunoprotective potential of its pilus components have not been studied yet. Using a selective proteomics approach, we have identified a surface protein of serotype 2 S. suis showing features of an ancillary pilus subunit, as evidenced by bioinformatics analysis, immunoblot and immunoelectron microscopy. Immunization with recombinant fragments of this protein, designated herein as PAPI-2b, markedly protected mice from systemic S. suis infection.

An unusual right heart mass.

A mobile right atrial mass, prolapsing into the right ventricle and extending to the inferior vena cava, was unexpectedly discovered during a routine echocardiographic examination in a 53-year- old woman. A possible tumour was suspected, but no evidence of primary malignancy was detected in lungs, liver, kidneys and adrenal glands. The patient underwent surgery, and only histological examination of the mass provided a final diagnosis of thrombosis.

PIK3CA mutations and BRCA1 expression in breast cancer: potential biomarkers for chemoresistance.

Mutations in PIK3CA and alterations of BRCA1 expression are common in breast cancer and have been correlated with altered sensitivity to taxanes in human cancer cell lines and with outcome of patients. We assessed mutations in the three hotspots of PIK3CA (E542K, E545K and H1047R) and intratumoral BRCA1 mRNA expression by quantitative RT-PCR in 61 breast cancer patients. Mutations of PIK3CA were found in 17 (27.9%) and did not correlate with BRCA1 transcript levels. Correlation with clinical and pathological features identified a significant association of mutations with older patients (P = 0.03). Higher BRCA1 mRNA expression was significantly correlated with advanced disease (P = 0.01) and ERBB2 overexpression (P = 0.02). These findings may help to identify a subgroup of patients who will likely benefit from chemotherapy regimens containing microtubule-disrupting agents.

Micropapillary carcinoma of the breast with necrosis-like cell death: a case report.

A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.

Abnormal nuclear structures (micronuclei, nucleoplasmic bridges, and nuclear buds) in a pleomorphic giant cell carcinoma of the stomach.

A rare case of pleomorphic giant cell carcinoma of the stomach in a 70-year-old man is reported. Characteristic microscopic findings included a general lack of architectural cohesiveness, aggregates of mononucleated or multinucleated giant cells, extensive areas of coagulative necrosis, and numerous mitoses. Immunohistochemically, tumor cells displayed cytoplasmic immunoreactivity for cytokeratin AE1/AE3 as well as overexpression of p53 and Ki-67. Electron microscopy revealed paranuclear tonofilaments bundles in giant cells confirming their epithelial nature. Furthermore, giant cells contained two or more nuclei with heterogeneous size, nucleoplasmic bridges, nuclear buds, and micronuclei. Similar abnormal nuclear structures have been closely related to breakage-fusion-bridge type of mitotic disturbances in tumor cell lines, and have not been previously reported in a human tumor.

Changes induced by exposure of the human lung to glass fiber-reinforced plastic.

The inhalation of glass dusts mixed in resin, generally known as glass fiber-reinforced plastic (GRP), represents a little-studied occupational hazard. The few studies performed have highlighted nonspecific lung disorders in animals and in humans. In the present study we evaluated the alteration of the respiratory system and the pathogenic mechanisms causing the changes in a group of working men employed in different GRP processing operations and exposed to production dusts. The study was conducted on a sample of 29 male subjects whose mean age was 37 years and mean length of service 11 years. All of the subjects were submitted to a clinical check-up, basic tests, and bronchoalveolar lavage (BAL); microscopic studies and biochemical analysis were performed on the BAL fluid. Tests of respiratory function showed a large number of obstructive syndromes; scanning electron microscopy highlighted qualitative and quantitative alterations of the alveolar macrophages; and transmission electron microscopy revealed the presence of electron-dense cytoplasmatic inclusions indicating intense and active phlogosis (external inflammation). Biochemical analyses highlighted an increase in protein content associated with alterations of the lung oxidant/antioxidant homeostasis. Inhalation of GRP, independent of environmental concentration, causes alterations of the cellular and humoral components of pulmonary interstitium; these alterations are identified microscopically as acute alveolitis.