BACKGROUND: NKX2-1-related disorders (NKX2-1-RD) are rare conditions affecting lung, thyroid, and brain development, primarily caused by pathogenic variants or deletions in the NKX2-1 gene. Congenital hypothyroidism (CH) is a common endocrine manifestation, leading to irreversible intellectual disability if left untreated.
OBJECTIVE: The aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD.
METHODS: This systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers.
RESULTS: Out of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging.
CONCLUSIONS: This review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.

BACKGROUND: Urticaria is one of the most common causes of emergency room visits. It is defined as an acute inflammatory dermatosis, characterized by localized degranulation of mast cells, with consequent dermal microvascular and formation of edematous and pruritic plaques called hives. Urticaria affects the skin and tissues of the superficial mucosa. Sometimes it is accompanied by angioedema, which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome. About 15%-25% of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16% and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention.
METHODS: We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes, irregular borders, with interlesional confluence, that were non-painful, without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner. He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids. Imaging studies demonstrated nodules in the lower lingula segment, at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology. Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion. The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1 (TTF-1) with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma. Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma.
CONCLUSIONS: Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature. In the presented case, a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1. According to the Curth criteria, the urticaria presented by the patient is related to the oncological diagnosis. In addition, the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria. Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Neurohypophysis granular cell tumor (NGCT) is a rare entity and is classified under thyroid transcription factor 1 (TTF-1) expressing tumors of pituitary. It is considered as an uncommon differential during sellar and suprasellar mass evaluation. Its intraoperative squash cytology is distinct and has rarely been reported in literature. A 65-year-old female presented with reduced vision of right eye and history of seizures. Radiological findings revealed a sellar/suprasellar mass with mass effect on optic chiasma. Intraoperative squash neurocytology examination showed a spindle cell lesion with abundant granular cytoplasm in tumor cells. Subsequent histopathology and immunohistochemistry confirmed the diagnosis of granular cell tumor. Granular cell tumor remains one of the sellar/suprasellar surprises. Its intraoperative neurocytology is unique and should be considered while evaluating a sellar/suprasellar mass. A case of sellar granular cell tumor with its intraoperative squash cytology, histopathology along with a review of literature is being presented with special emphasis on cytological differential diagnosis in pituitary region.

OBJECTIVE: To explore the association of thyroid transcription factor-1 (TTF-1) expression status with clinicopathological characteristics and survival of patients with small cell lung cancer (SCLC).
METHODS: A comprehensive literature search was conducted to identify potentially relevant studies in several electronic databases, including EMBASE, PubMed, Web of Science, CNKI and WanFang. The relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the relation of TTF-1 with clinicopathological parameters and prognosis, respectively. Sensitivity analysis was performed to assess the stability of the pooled results. Begg\'s funnel plot and Egger\'s test were applied to detect the publication bias. All statistical analyses were performed by STATA 12.0 version software.
RESULTS: A total of 11 studies involving 1786 SCLC patients were included in our study. No significant relationship between TTF-1 and any clinicopathological features was observed. However, the pooled results demonstrated that TTF-1 expression indicated prolonged overall survival (OS) (HR = 0.56, 95% CI: 0.45-0.70; P < 0.001) and progression-free survival (PFS) (HR=0.41, 95% CI: 0.28-0.62; P < 0.001). Subgroup analysis stratified by the country manifested that the significant prognostic value of TTF-1 expression status was only observed in SCLC patients who from China.
CONCLUSIONS: TTF-1 might be an independent prognostic factor in SCLC patients, especially patients who were from China. More well-designed prospective studies are needed to further testify our findings.

Spindle cell oncocytoma (SCO) is a newly described rare entity simulating clinicoradiological features of a nonfunctional pituitary adenoma and is corresponding to the category of World Health Organization grade I tumor. However, because of the reported incidence of recurrence and invasive presentation in some cases, its categorization as a low grade tumor is questionable. Earlier, it was thought to arise from the folliculostellate cells of adenohypophysis. Recently, few reports have described expression of thyroid transcription factor-1 [TTF-1], which is a specific marker for pituicytes of neurohypophysis, suggesting this tumor to be a variant of pituicytoma. We describe a case of SCO in a 28-year-old young female patient with TTF-1 immunopositivity, and ultra-structurally showing abundant mitochondria along with few neurosecretory granules.

BACKGROUND: Thyroid follicular carcinoma-like renal tumor (TFCLRT) is a rare primary renal epithelial tumor that was first reported in 2006. We report a case diagnosed of TFCLRT by us to observe the pathological feature and analyze comparatively the clinical and pathologic characteristics with all cases of reviewed literatures.
METHODS: A 54-year-old female patient had the urinary frequency with the symptom of right flank pain with a history of more than half a year of hypertension and received uterine fibroid resection 12 years ago. B-mode ultrasound examination and renal magnetic resonance showed a right renal sinus nodule.
METHODS: Histopathology revealed thyroid follicle-like structures of different sizes, containing a colloid-like substance, while the periodic acid-Schiff (PAS) and diastase-resistant PAS staining confirmed that it was mucus protein. Immunohistochemical staining showed that it expresses the transcription factor PAX-8 but does not express the thyroid-specific antibodies TG and TTF-1.
METHODS: The patient underwent a tumor enucleation of right kidney. No other treatment was conducted after surgery.
RESULTS: No metastases to lymph nodes and other organs were found, and 9-months of follow-up did not reveal any tumor progression.
CONCLUSIONS: We should differentially diagnose the renal metastasis of thyroid follicular carcinoma or papillary carcinoma. Some related literatures reported that the tumour cells had significant heteromorphism, several of which metastasized to lymph nodes or distal organs. Its biological behavior need to be studied intensively by further expanding the number of cases.

BACKGROUND: Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare malignant nasopharyngeal tumor with features resembling papillary thyroid carcinoma including nuclear positive expression of thyroid transcription factor-1 (TTF-1).
METHODS: A 64-year-old male presented with nasal bleeding and a foreign body sensation of the nasopharynx. Laryngoscopy revealed a 2.0-cm broad-based mass with a smooth surface on the posterior wall of the nasopharynx. A biopsy was obtained.
METHODS: Histopathologic examination demonstrated tumor cells arranged in both papillary and glandular architecture. The tumor cells express nuclear immunoreactivity for TTF-1. The diagnosis of TL-LGNPPA was made.
METHODS: After the patient was diagnosed with TL-LGNPPA, he underwent complete surgical resection.
RESULTS: There was no recurrence or evidence of metastatic disease at the 12-month follow-up.
CONCLUSIONS: TL-LGNPPA is easy to misdiagnose as metastatic papillary thyroid carcinoma or other relative primary adenocarcinomas. It is important to have a broad differential diagnosis and know the key features of each entity because the prognosis and clinical treatment of each may differ.

Solitary fibrous tumor (SFT) is a derived mesenchymal tumor from spindle cells, mostly occurred in the pleura. To analyze the clinical features of the SFT, data for a patient with SFT that involved in the pleura were retrospectively analyzed by assisted thoracoscope in the Affiliated Hospital of Zunyi Medical College in August 2015. The male patient was 45 years old, who showed the main clinical symptoms of chest pain, cough, sputum, and dyspnea. Large amount of right pleural effusion, chest space-occupying lesions were found by chest CT, suggesting a malignant tumor with metastasis at the 2nd and 3rd right rib. Immunohistochemical results showed: CD34 (+), cytokeratin (-), cytokeratin 5/6 (-), calretinin (-), epithelial membrane antigen(-), mesothelial cell (-), vimentin (++), Wilm\'s tumor-1 (+), Bcl-2 (+), CD56 (-), CD99 (+), desmin (-), and thyroid transcription factor-1 (-). It was diagnosed as SFT at right side wall layer pleura. SFT is a rare disease and it may occur at any site in the body. It lacks characteristic clinical symptoms and can be asymptomatic, or displays symptoms such as cough, chest pain, dyspnea, and hemoptysis. SFTs can only be conclusively diagnosed based on histopathologic and immunohistochemical characteristics of the tumor, and they are mostly benign. The main treatment for SFTs is the complete surgical resection. The prognosis for this disease is relatively good.
孤立性纤维性肿瘤(solitary fibrous tumor，SFT) 是一种来源于间叶细胞的梭形细胞肿瘤，大多发生于胸膜。为分析累及胸膜的SFT临床特征，回顾性分析遵义医学院附属医院2015年8月经内科胸腔镜检查确诊的1例累及壁层胸膜的SFT临床资料。该患者为男性，45岁，首诊主要症状为胸痛、咳嗽、咳痰、气促半月；胸部CT检查见右侧胸腔大量积液，部分包裹，胸腔占位性病变，右肺部分肺不张，考虑恶性肿瘤，疑右侧2、3肋骨转移；活组织病理检查免疫组织化学结果示CD34(+)；细胞角蛋白(cytokeratin，CK)(–)，CK 5/6(–)，细胞内钙结合蛋白(calretinin，CR)(–)，上皮膜抗原(epithelial membrane antigen，EMA)(–)，间皮细胞(mesothelial cell，MC)(–)，波形蛋白(vimentin，Vim)(++)；肾母细胞瘤(Wilm’s tumor-1，WT-1)(+)，Bcl-2(+)，CD56(–)，CD99(+)，结蛋白(desmin)(–)，甲状腺转录因子-1( thyroid transcription factor-1，TTF1)(–)。诊断为右侧壁层胸膜SFT。SFT是一种少见疾病，可发生于全身各部位，临床症状无特异性，可无症状或咳嗽、胸痛、呼吸困难、咯血等；确诊需病理和免疫组织化学结果，多为良性；治疗以手术完整切除肿瘤为主，预后相对较好，需长期随访。.

Objective: To study the clinicopathologic features of thyroid-like follicular renal cell carcinoma. Methods: Clinical data were collected in 5 cases of thyroid-like follicular renal cell carcinoma. HE staining and immunohistochemistry were carried out in surgically-removed specimen to analyze the clinical and pathological features with review of the literatures. Results: The patients aged 20-55 years, with one male and four females; the tumor occurred in the left kidney in three cases and right kidney in two cases. One case had a history of thyroid papillary carcinoma 3 years ago, and the patient had left flank pain, macroscopic haematuria for 2 weeks. The rest four cases had no consciousness of clinical symptoms and signs, without history of thyroid gland surgery; the physical examination found a mass in the kidney and normal thyroid glands. Three patients underwent radical nephrectomy, and the other two patients underwent tumor partial nephrectomy. The tumors were 2-4 cm in size. They showed a solitary nodular mass of well circumscribed with taupe and gray on cut surface. Microscopically, most of tumor cells arranged in thyroid follicular pattern in different sizes, with papillary configuration in a small portion, in four cases; the follicular structure was intermixed with the papillary each half in one case. A large amount of thyroid colloid was deposited within follicule-like structure or papillary axis, lined by simple columnar cells or cubic cells, with obvious atypia, ground-glass nuclei, nuclear groove and rare mitosis. Immunohistochemical staining showed tumor cells were positive for PAX8, and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin (Tg). One of five patients presented with lymph node metastases (4/4) of renal hilum the same time in the diagnosis. Five cases were followed up for 5-84 months after operation, and no tumor progression was found. Conclusions: Thyroid-like follicular renal cell carcinoma is primary renal epithelial malignant tumor. The diagnosis mainly depends on its characteristics of histological appearance, namely similar to the histological morphology of well-differentiated thyroid follicular carcinoma and papillary carcinoma, and the metastasis from the thyroid papillary or follicular carcinoma must be excluded. On the premise of clinical history, immunohistochemical markers TTF1 and Tg have certain value in the differential diagnosis.

Low-grade papillary adenocarcinomas with expression of thyroid transcription factor-1 (TTF-1) are rare tumors of the nasopharynx, with only a few cases reported in the literature. These tumors have an excellent prognosis following complete surgical excision. We report a 13-year-old boy with this rare tumor in the nasopharynx. The patient underwent complete surgical excision of the tumor and was on follow-up without evidence of recurrence.