OBJECTIVE: To screen for pathogenic variants in the coding regions of STK11 gene among Chinese patients with Peutz-Jeghers syndrome (PJS). METHODS: Peripheral blood samples were collected from 64 patients. The coding regions of the STK11 gene were detected by PCR and Sanger sequencing. RESULTS: Fourty-eight patients were found to harbor STK11 gene variants, which included 39 types of variants consisting of missense, nonsense, insertional, deletional and splice site variants. Among 64 PJS patients, the detection rate of point variants was 75.00% (48/64), of which missense variants accounted for 29.17% (14/48), nonsense variants accounted for 29.17%(14/48), insertion variants accounted for 2.08% (1/48), deletional variants accounted for 10.42% (5/48), and splice site variants accounted for 29.17% (14/48). The detection rates of sporadic cases and those with a family history were 71.8% (28/39) and 80.0% (20/25), respectively. Two variants (c.250A>T, c.580G>A) occurred in 3 PJS probands. Thirteen variants were unreported previously and were considered to be pathogenic. CONCLUSION The detection rate of variants among Chinese PJS patients is similar to that of other countries. A number of novel common variant sites were discovered, which enriched the spectrum of PJS-related variants.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Humans ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11–17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Adenoma ; Biopsy ; Carcinoma, Squamous Cell ; Cervix Uteri ; Female ; Gastrointestinal Tract ; Humans ; Incidence ; Mucins ; Peutz-Jeghers Syndrome ; Pigmentation ; Polyps ; Uterine Cervical Neoplasms

Segmental neurofibromatosis, a subtype of neurofibromatosis type 1, is characterized by neurofibromas and/or café-au-lait spots limited to an area or segment of the body. Checkerboard pattern is a rare type of cutaneous mosaic manifestation, characterized by squares or broad ribbons of affected skin with sharp demarcation at the midline. Herein, we report the case of a patient with bilateral segmental neurofibromatosis with lentiginosis showing a checkerboard pattern. Our patient had multiple hyperpigmented macules on her entire body in a checkerboard pattern since birth. Several café-au-lait patches were observed on the left buttock and right axilla. A neurofibroma was incidentally found beneath the café-au-lait patch by histological examination, which showed ill-defined spindle cells with elongated nuclei at the deep dermis that stained positive for S-100. Based on the clinical presentation and histopathologic results, the patient was diagnosed with bilateral segmental neurofibromatosis with lentiginosis showing a checkerboard pattern.
Axilla ; Body Patterning ; Buttocks ; Dermis ; Humans ; Lentigo ; Neurofibroma ; Neurofibromatoses ; Neurofibromatosis 1 ; Parturition ; Skin

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40–50%), SOS1 (10–20%), RAF1 (3–17%), and RIT1 (5–9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.
Congenital Abnormalities ; Costello Syndrome ; Diagnosis ; Ectoderm ; Electrocardiography ; Genitalia ; Genotype ; Heart Diseases ; Humans ; Hypertelorism ; Intellectual Disability ; Lentigo ; Noonan Syndrome ; Panthera ; Protein Kinases ; Puberty, Delayed ; Pulmonary Valve Stenosis ; Thorax

No abstract available.
Atrial Fibrillation ; LEOPARD Syndrome* ; Panthera*

No abstract available.
Lentigo* ; Ustekinumab*

A 69-year-old man presented with a black irregular patch on his left cheek. Skin biopsy revealed lentigo maligna melanoma in situ. He was treated via partial excision of the melanoma, followed by the application of 5% imiquimod cream every other night for 6 to 8 hours. The patient experienced severe local inflammation accompanied by burning, edema, and erythema, as well as oozing and crusting. The patient discontinued using the imiquimod cream after 15 applications because of the inflammation. Depigmentation was noted in the treated area 3 months after the initiation of treatment with imiquimod cream. Histological examination using Melan-A staining of the depigmented area revealed an absence of melanocytes, which is consistent with vitiligo. The depigmented lesions improved considerably after a 5-year follow-up, and there was no recurrence of melanoma.
Aged ; Biopsy ; Burns ; Cheek ; Edema ; Erythema ; Follow-Up Studies ; Humans ; Hutchinson's Melanotic Freckle* ; Inflammation ; Lentigo* ; MART-1 Antigen ; Melanocytes ; Melanoma* ; Recurrence ; Skin ; Toll-Like Receptors ; Vitiligo

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.
Adenocarcinoma* ; Cervix Uteri* ; Diagnosis, Differential ; Early Diagnosis ; Female ; Follow-Up Studies ; Genetic Testing ; Humans ; Hysterectomy ; Mass Screening ; Medical Records ; Multivariate Analysis ; Peutz-Jeghers Syndrome ; Retrospective Studies ; Uterine Cervical Neoplasms

Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently represent a diagnostic and management challenge. Small bowel tumors are generally classified as epithelial, mesenchymal, lymphoproliferative, or metastatic. Familial adenomatous polyposis and Peutz-Jeghers syndrome are the most common inherited intestinal polyposis syndromes. Until the advent of capsule endoscopy (CE) and device-assisted enteroscopy (DAE) coupled with the advances in radiology, physicians had limited diagnostic examination for small bowel examination. CE and new radiologic imaging techniques have made it easier to detect small bowel tumors. DAE allows more diagnosis and deeper reach in small intestine. CT enteroclysis/CT enterography (CTE) provides information about adjacent organs as well as pictures of the intestinal lumen side. Compared to CTE, Magnetic resonance enteroclysis/enterography provides the advantage of soft tissue contrast and multiplane imaging without radiation exposure. Treatment and prognosis are tailored to each histological subtype of tumors.
Adenomatous Polyposis Coli ; Capsule Endoscopy ; Diagnosis ; Gastrointestinal Tract ; Intestinal Polyposis ; Intestine, Small ; Peutz-Jeghers Syndrome ; Prognosis ; Radiation Exposure

To explore the clinical features, pathological features, gene test results, diagnosis, treatment and prognosis of Peutz-Jeghers syndrome(PJS).
 Methods: We retrospectively analyzed clinical data of 46 hospitalized cases of PJS during 2007 and 2017.
 Results: All 46 patients had mucocutaneous melanin pigmentation and multiple gastrointestinal polyposis. The pigmentation was first noticed often within 5 years old, and 14 cases had family history. The clinical manifestations mainly included black spots, abdominal pain, hematochezia, and anemia. Histological examinations showed that 20 patients were classified as hamartomatous polyps,18 as adenomatous polyps, 14 as inflammatory polyps, and 10 as zigzag polyps. Eleven patients sequenced a panel of 20 genes previously associated with colorectal cancer (CRC) by next-generation sequencing, and the results showed 5 patients with gene mutations, and 3 of them with intussusception and surgical histories were found to have pathogenic germline mutations in the STK11 gene. Endoscopic treatment was the main therapy, but endoscopy combined with laparoscopy or surgical treatment was performed when complications occurred or the polyp was too large. Malignant tumors were found in 3 patients during follow-up.
 Conclusion: PJS is a hereditary disease which is characterized by spots of the skin or mucosa and gastrointestinal multiple polyps. The main pathological features are hamartoma and adenoma. The risks for intussusception and surgical operation are found to be high in the patients with pathogenic germline mutations in the STK11 gene. Endoscopic treatment is the main therapy. PJS patients should be followed up regularly due to the increasing risk for cancer and being easily to relapse.
Child, Preschool ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Neoplasm Recurrence, Local ; diagnosis ; pathology ; surgery ; therapy ; Peutz-Jeghers Syndrome ; diagnosis ; surgery ; therapy ; Protein-Serine-Threonine Kinases ; genetics ; Retrospective Studies