ABSTRACT
Background
The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this ...recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular‐derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM.
Methods
Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed.
Results
A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors.
Conclusion
The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback.
Quality metric tools in thyroid cytology can offer valuable feedback to individual cytopathologists and laboratories, contributing to improving diagnostic practices.
Background
ThyroSeq assesses the probability of malignancy (POM) in thyroid fine‐needle aspiration cytology specimens diagnosed as atypia of undetermined significance (AUS). The authors investigated ...whether defined AUS subcategories are associated with specific molecular alterations, the molecular‐derived risk of malignancy (MDROM), and the risk of malignancy (ROM).
Methods
Fine‐needle aspiration cytology reports of AUS and corresponding results from the ThyroSeq version 3 genomic classifier results were retrieved and subcategorized as follicular cells with either cytologic atypia (FC‐C), architectural atypia (FC‐A), both cytologic and architectural atypia (FC‐CA), or a predominance of Hurthle cells (PHC). The MDROM, ROM, and frequency of molecular alterations by subcategory were computed and analyzed, and p < .05 was considered significant.
Results
The final analysis included 541 cases subdivided into 233 with FC‐A, 104 with FC‐C, 116 with FC‐CA, and 88 with PHC. The benign call rate and positive call rate for the AUS category were 72% and 28%, respectively, which varied between AUS subcategories. The MDROM by subcategory was 15.9% FC‐A, 20.5% FC‐C, 33.8% FC‐CA, and 14.4% PHC. Histologic follow‐up was available for 155 (28%) AUS cases with a follow‐up period ≥12 months. The 95% confidence intervals of the MDROMs overlapped with the ROMs. The highest MDROM and ROM were in the FC‐CA subcategory. RAS mutations were present in all subcategories. BRAF V600E mutations and papillary thyroid carcinoma were most frequent in the FC‐CA subcategory. Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features was significantly more frequent in the FC‐C subcategory.
Conclusions
The current results demonstrated that AUS subcategories are associated with specific genetic alterations, the MDROM, and the ROM. Molecular results and an awareness of various cancer probabilities within AUS subcategories can allow for a more tailored management.
Fine‐needle aspiration cytology subcategories of atypia of undetermined significance have been associated with different probabilities of malignancy and risks of malignancy and are characterized by different molecular alterations. Molecular results and an awareness of various cancer probabilities within atypia of undetermined significance subcategories can allow more tailored management.
Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular ...drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management.
Abstract
Objectives
Amputation due to gangrene and arthroplasty for degenerative joint disease are common orthopedic procedures and are expected to increase as populations age. Histopathologic ...examination of these specimens can identify unsuspected diseases.
Methods
We reviewed gangrenous amputations and large joint arthroplasty specimens for diagnosis of unexpected lymphoma, January 2014 to January 2020. Pathology and medical records were reviewed to determine diagnosis, treatment, and outcome.
Results
Five cases (0.08%) of unexpected primary extranodal marginal zone lymphoma (MZL) centered in bone were identified in 1,624 amputations for gangrene and 4,163 arthroplasty specimens. The female-to-male distribution was 3:2. Median age was 71 years (range, 62-87). The 3 cases arising in the setting of gangrene involved the first toe phalanges and metatarsals, and the femoral head was involved in all cases of joint disease (2 cases). The bone showed variable (10%-80%) infiltration by dense populations of small lymphoid cells with MZL immunophenotype. One patient died from sepsis 18.5 months after diagnosis; all others are alive with a median follow-up of 27.45 months.
Conclusions
Histopathologic examination of nonneoplastic orthopedic specimens identifies unexpected primary bone extranodal MZL in a small percentage of cases. This neoplasm may be the result of chronic antigenic stimulation in some circumstances.
Primary sarcomas of the larynx are rare and are associated with diagnostic and treatment challenges. Studies of these tumors are limited, and most examples have been reported as small series. To ...further increase our understanding of laryngeal sarcomas, we reviewed our experience of an adult cohort. A retrospective search for laryngeal sarcomas from our pathology archives and consultation files of one of the authors was performed. We studied 27 primary laryngeal sarcomas that included 25 males, and 2 females, with a mean age of 60 years (range 33–85). The cases included conventional chondrosarcoma (16), well-differentiated liposarcoma (2), clear cell chondrosarcoma (1), leiomyosarcoma (2), high grade myxofibrosarcoma (2), high grade myofibroblastic sarcoma (1), low-grade myofibroblastic sarcoma (1), malignant granular cell tumor (1), and Kaposi sarcoma (1). Data on treatment and follow-up was available in 17 and 16 cases, respectively. 12 patients underwent partial laryngeal resection; five had total laryngectomy, and the patient with Kaposi sarcoma received combined highly active antiretroviral therapy and chemotherapy. Three patients developed local recurrence, and two patients developed metastases. The remaining patients with follow up had a favorable outcome and were disease-free after treatment. The important differential diagnosis of spindle cell sarcoma is sarcomatoid squamous cell carcinoma, and their distinction often requires extensive sampling of the mucosal surface and immunohistochemical analysis. The mainstay of treatment for laryngeal sarcomas is surgical removal, with the extent dictated by tumor type and grade. Adjuvant therapy is reserved for high-grade sarcomas and may be given in a neoadjuvant or adjuvant setting.
Abstract
Objectives
Epithelioid sarcoma (ES) rarely arises in the nerve. To increase our understanding of this unusual tumor originating in the nerve, we describe the features of three cases and ...review the literature.
Methods
Clinical data, imaging, pathology, treatment, and follow-up are detailed. A systematic literature review was conducted.
Results
Two patients were male and one female; the median age was 24 years. The patients had neurologic symptoms, and the tumors arose in large nerves and ranged from 2.4 to 5.8 cm. The tumors were avid on positron emission tomography–computed tomography and showed increased signal intensity on T2-weighted magnetic resonance imaging. Centered in the nerve, the tumors grew with an infiltrative pattern and encased the nerve fascicles. All were treated with wide resection, and adjuvant treatment included combinations of chemotherapy and radiation. One recurred, and the limb was amputated. Metastases were documented to lymph nodes, lung, pleura, and skin. One patient died of disease after 54 months. Literature review including our cases showed that tumors stained with pancytokeratin (9/9), EMA (4/4), and CD34 (7/7); there was loss of INI1 in all six cases tested.
Conclusions
ES rarely arises in the peripheral nerve, and its infiltrative nature often requires morbid surgery. The differential includes a variety of benign and malignant epithelioid neoplasms.
Background
Basaloid salivary gland neoplasm of uncertain malignant potential (B‐SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign ...neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid‐based cytology (LBC) specimens.
Methods
In total, 45 B‐SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative.
Results
PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1‐positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex‐PA. PLAG1‐equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%.
Conclusions
PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1‐positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1‐negative/equivocal tumors should remain in the B‐SUMP category.
PLAG1 immunocytochemistry is useful for the diagnosis of pleomorphic adenoma when strong/diffusely positive and can be reliably performed directly on alcohol‐fixed conventional smears and liquid‐based cytology specimens. It may help enhance diagnostic accuracy in challenging cases and reduce indeterminate diagnoses.
Background
Sinonasal adenosquamous carcinoma is rare, and there are almost no studies detailing morphology or characterizing their genetic driver events. Further, many authors have termed sinonasal ...tumors with combined squamous carcinoma and glands as mucoepidermoid carcinoma but none have analyzed for the presence of
MAML2
rearrangement.
Methods
Cases from 2014 to 2020 were collected and diagnosed using World Health Organization criteria. They were tested for p16 expression by immunohistochemistry (70% cut-off),
DEK::AFF2
fusion by fluorescence in situ hybridization (FISH) and AFF2 immunohistochemistry,
MAML2
rearrangement by FISH, and low- and high-risk HPV by RNA ISH and reverse transcription PCR, respectively. Detailed morphology and clinical features were reviewed.
Results
There were 7 male (64%) and 4 female (36%) patients with a median age of 69 years, most Caucasian (10 of 11 or 91%). Most had tobacco exposure (8/11, 73%) and most presented with epistaxis, a visible nasal mass, and/or facial pain. Several had a precursor papillomas (3 of 11, 27%). The squamous component had variable keratinization, 5 of 11 (46%) of which would be described as keratinizing, 3 non-keratinizing, and 2 with mixed features. All had gland formation, by definition, and 2 of 11 (18%) had ciliated tumor cells. None of the 11 cases had
MAML2
rearrangement and one had
DEK::AFF2
fusion with associated positive nuclear AFF2 protein immunostaining. Most were p16 positive (7 of 11, 64%) and all 7 of these were hrHPV positive either by RNA ISH or RT-PCR. Two of the p16-negative tumors were positive for lrHPV by RNA ISH. Treatment included surgery alone (4 of 11, 36%), surgery with adjuvant radiation (5 of 11, 45%), and surgery with radiation and chemotherapy (2 of 11, 18%). Four of 11 patients (36%) suffered disease recurrence, two requiring re-operation and who were disease free at last follow-up, one receiving additional chemotherapy and who was alive with disease. The other elected to undergo palliative therapy and died of disease.
Conclusion
Sinonasal adenosquamous carcinoma is a somewhat heterogeneous tumor not infrequently arising ex papilloma and having various drivers including high- and low-risk HPV and rarely
DEK::AFF2
fusion. The prognosis appears favorable when proper treatment is possible.
Cervical thymic cysts (CTCs) represent 1% of all cervical cystic masses. A review of the literature found that CTCs are typically asymptomatic, with a propensity to be left sided. CTCs often require ...histological evaluation for diagnosis. A 27-year-old male patient presented to an outpatient otolaryngology clinic with worsening bilateral jaw and neck pain and an incidental right-sided neck mass found on cervical MRI. Preoperative differential diagnosis included venolymphatic malformation versus branchial cleft cyst. Histological examination of the excised specimen provided diagnosis of a CTC. Postoperatively, the patient reported improvement in cervical pain. CTCs are a rare cause of lateral neck mass in young adults. Typical presentation included neck enlargement with no symptoms or in some cases compressive symptoms. It is important to consider CTCs when formulating a differential for a lateral neck mass.
