Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Lupus Erythematous Profundus: An Unusual Manifestation in the Otolaryngological Setting.

Lupus erythematous profoundus (LEP) is an uncommon manifestation of chronic lupus erythematous (CLE) involving inflammation of the subcutaneous fat and deep dermis. It is rarely seen in the otolaryngological practice. We describe a case of a 33-year-old female who presented with bilateral acute onset cheek swelling, which led to the unexpected diagnosis of LEP. We describe the diagnostic pitfalls that may potentially bias the surgeon towards the management of such patients.

A clinical conundrum: Temporal bone metastases from lung adenocarcinoma.

BACKGROUND: Metastatic disease to the temporal bone is rare. Even more uncommonly, it can be the first manifestation of an underlying malignancy. Patients typically present late in the disease process with non-specific symptoms of hearing loss, facial nerve palsy and otorrhea. CASE: A 62-year-old Chinese female presented with right facial weakness, which had near-complete improvement in response to pulse prednisolone. On examination, she had a right temporal swelling and right mild-severe conductive hearing loss. A computed tomography scan showed a destructive lesion centred in the squamous temporal bone, with an associated soft tissue component. Positron emission tomography scan revealed bony and lung metastases, but no distinct hypermetabolic primary site. An incisional biopsy unexpectedly returned as metastatic lung adenocarcinoma. CONCLUSION: Although rare, it is important for otolaryngologists to be aware of the insidious nature of temporal bone metastases and possible atypical clinical and radiological features, to facilitate timely workup and initiation of treatment.

Insulin Allergy to Detemir Followed by Rapid Onset of Diabetic Ketoacidosis: A Case Report and Literature Review.

The management of diabetes mellitus in an insulin-dependent patient is challenging in the setting of concomitant antibody-mediated-insulin hypersensitivity. We report a case of a 62-year-old woman with pre-existing type 2 diabetes mellitus of 10 years duration who developed type 3 hypersensitivity reaction to insulin analogue detemir, and subsequently, severe diabetic ketoacidosis (DKA). She was C-peptide negative and was diagnosed with insulin-dependent diabetes. Despite increasing dose adjustments, insulin-meal matching, and compliance with insulin, she experienced episodes of unexpected hyperglycaemia and hypoglycaemia. The development of rash after detemir initiation and rapid progression to DKA suggests an aberrant immune response leading to the insulin allergy and antibody-induced interference with insulin analogues. Glycaemic control in the patient initially improved after being started on subcutaneous insulin infusion pump with reduced insulin requirements. However, after a year on pump therapy, localised insulin hypersensitivity reactions started, and glycaemic control gradually deteriorated.

A novel NSDHL variant in CHILD syndrome with gastrointestinal manifestations and localized skin involvement.

BACKGROUND: CHILD syndrome is an X-linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. METHODS AND RESULTS: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. CONCLUSION: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Expect the Unexpected: Report of a Case of Pediatric Pharyngeal Extraosseous Plasmacytoma with Tumefactive Amyloidosis ("Amyloidoma") and a Review of the Literature.

We report a rare case of localized pharyngeal tumefactive amyloidosis caused by extraosseous plasmacytoma in a 12 year-old girl who presented with otalgia, sore throat and blood stained sputum. The tumor was predominantly composed of amyloid with a limited component of well-differentiated neoplastic plasma cells, which were monoclonal (kappa restricted) on light chain in-situ hybridization. The amyloid deposits were positive for kappa immunoglobulin light chain on immunohistochemistry. The patient was treated with a combination of surgery and radiotherapy. Follow-up at 1 year showed no evidence of recurrence or progression.

An intraosseous sclerosing odontogenic tumor predominantly composed of epithelial cells: relation to (so-called) sclerosing odontogenic carcinoma and epithelial-rich central odontogenic fibroma.

We report a case of an asymptomatic sclerosing odontogenic tumor in a 31-year-old woman. Radiologically, the tumor was well circumscribed, was predominantly radiolucent, and had a peripheral sclerotic margin. Histopathologically, the tumor showed small clusters, strands, and cords of small to medium-sized epithelial tumor cells in a sclerotic collagenous stroma. Immunohistochemically, the tumor cells were positive for broad-spectrum cytokeratins (CKs) (CK7, CK5/6, CK19, and CAM 5.2) and p63. Membranous staining for E-cadherin was present. There was weak to moderate nuclear expression of p16 in 30% of cells. Rare tumor cells were positive for p53. Progesterone receptors were expressed in about 60% of the tumor cells. The proliferative activity (Ki-67) was approximately 2%. A molecular genetic (fluorescence in situ hybridization) study showed no EWSR1 (EWS RNA-binding protein 1) gene rearrangement. No recurrence or metastatic events have been documented at 1-year follow-up. This tumor represents a classification dilemma mainly between epithelial-rich central odontogenic fibroma and the so-called sclerosing odontogenic carcinoma.

Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation.

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Muco-submucosal elongated polyps of the gastrointestinal tract: a case series and a review of the literature.

We present three cases of gastrointestinal muco-submucosal elongated polyps, two located in the duodenum and one in the descending colon. All three cases had a characteristic, "worm-like" endoscopic appearance and were lined by unremarkable mucosa. The vascular component was located in the submucosa and was composed of a mixture of variably dilated blood vessels (capillaries and veins) and lymphatics. The duodenal polyps displayed lipomatous metaplasia of the submucosal stroma. The dual vascular phenotype of the vascular component was confirmed by immunohistochemistry with D2-40 and CD31.

Fibro-osseous pseudotumor of the digit: Presentation as an enlarging erythematous cutaneous nodule.

Fibro-osseous pseudotumor of the digit is an unusual ossifying fibro-proliferative lesion. The current case is a 54-year-old woman who presented with an enlarging reddish nodule on the distal aspect of her left big toe. Excision biopsy was performed and the histopathology featured a dermal-centered lesion composed of osteoblast-rimmed bony trabculae lying amidst fibrovascular stroma. This entity resembles and may be within the spectrum of myositis ossificans, the prototype post-traumatic reactive fibro-osseous proliferation, although the latter is typically more proximally located and features a zonation pattern on histopathology. The distinguishing features from other pathological differential diagnoses, such as subungual exostosis and extraskeletal osteosarcoma, are discussed. The growth is considered benign and local recurrence following complete excision is unusual.