A Large Adult Postcricoid Lymphatic Malformation: A Case Report and Literature Review.

Adult-onset lymphatic malformations arising at the postcricoid, a subsite of the hypopharynx, are sporadic. Only one case has been previously reported. In this study, we presented a 36-year-old female presented with globus sensation, dysphagia, and upper airway obstruction, requiring a tracheostomy. A computed tomography scan identified a 5 cm × 4.5 cm × 3 cm multilocular hypodense lesion in the postcricoid. Due to its considerable size, complete resection with function preservation was crucial, and a standard microscopic direct laryngoscopy approach may result in inadequate exposure, while an open transcervical approach may affect functional outcomes and increase surgical complications. We successfully performed an en bloc resection with a transoral endoscopic approach, using laryngeal suspension and a laparoscopic ultrasonic scalpel to preserve aerodigestive functions, ensure rapid recovery, and avoid neck scarring. The patient was decannulated within 2 weeks and remained disease-free after 1 year. The reported cases of adult-onset lymphatic malformations at the postcricoid and hypopharynx were reviewed and summarized for educational purposes.

Characterization of "suspicious for malignancy" for non-papillary carcinoma diagnoses on thyroid fine-needle aspiration.

INTRODUCTION: To evaluate the incidence, risk of malignancy, and management of "suspicious for malignancy" (SFM) for non-papillary carcinoma diagnoses according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). MATERIALS AND METHODS: A retrospective search was performed for all thyroid fine-needle aspirations (FNAs) with an SFM diagnosis in the electronic Pathology database at The Johns Hopkins Hospital from 2000 to 2019. During this period, a total of 644 cases were diagnosed as SFM. Of these, 55 cases of "suspicious for non-papillary thyroid carcinoma" (SNPTC) were identified. These 55 cases were then compared with 65 random cases of "suspicious for papillary thyroid carcinomas" (SPTC) diagnoses as a control group. RESULTS: The SNPTC subgroup consisted of 28 cases of "suspicious for medullary thyroid carcinoma" (SMTC) (50.91%), 4 cases of "suspicious for metastasis" (SMET) (7.27%), 3 cases of "suspicious for malignant lymphoma" (SML) (5.45%), 2 cases of "suspicious for poorly-differentiated thyroid carcinoma" (SPDC) (3.64%), and 18 cases of "suspicious for malignancy, not otherwise specified" (SNOS) (32.73%). When compared to SPTC, SNPTC patients' average age was older (P = 0.004). Ancillary studies assisted in diagnosing SNPTC more so than SPTC (P < 0.001). Immunohistochemical studies were performed for 11 cases, molecular studies for 6 cases, and needle rinse calcitonin level for 1 case. When correlated with surgical follow-ups, the risk of malignancy (ROM) was 91.18% for SNPTC compared to 93.75 for SPTC%. CONCLUSIONS: SNPTC was rarely diagnosed when compared with SPTC. SMTC was the most commonly diagnosed SNPTC subgroup, followed by SNOS. The ROM of SNPTC was slightly lower than that of SPTC. Ancillary studies and previous clinical history, in addition to cytomorphology, was helpful when rendering the diagnosis of SNPTC.

Adenoid cystic carcinoma cytology: Salivary gland and nonsalivary gland.

OBJECTIVES: Adenoid cystic carcinoma (ACCA) is an uncommon primary malignancy of salivary glands and rarely nonsalivary tissue. This study aims to evaluate the diagnostic accuracy of ACCA on fine needle aspiration (FNA) material and the associated challenges. METHODS: A search on electronic pathology database from 2006 to 2016 at The Johns Hopkins Hospital found 83 cytology specimens diagnosed as ACCA, 49 with histology follow-up. RESULTS: Fifty-two females and 31 males were found ranging from 37 to 95 years old (mean 62.5). The tumor size was 1 to 11.5 cm (mean 3.4). FNAs were performed on 46 salivary glands (54.88%), 12 head and neck masses (14.45%), 9 lymph nodes (10.84%), 9 tracheas/lungs (10.84%), 4 vaginal/perineum/gluteal masses (4.82%), and one for each kidney, liver and abdominal/pelvic mass (1.21%). 83 FNA diagnoses revealed 3 nondiagnostics (3.61%), 20 neoplasms with unspecified features (24.10%), 30 basaloid neoplasms (36.14%), 18 ACCA (21.69%), and 12 other malignancies (14.46%). The accuracy of FNA in diagnosis of ACCA comparing to histologic follow-up in 49 cases was 87.5% sensitivity, 66.67% specificity, with 92.11% positive predictive value and 54.55% negative predictive value. The most common mimicker was pleomorphic adenoma. CONCLUSION: ACCA can be diagnosed not only in the salivary gland FNAs, but also respiratory tract, intra-abdominal, kidney, and gynecologic regions. FNA is a preferred technique to assess mass lesions. However, a diagnosis of ACCA on FNA material should be rendered with caution since there are benign and malignant neoplasms with overlapping features. Awareness of prior medical history and ancillary studies can improve the diagnosis.

Mesenchymal neoplasms of the tubular gut and adjacent structures: experience with EUS-guided fine-needle aspiration cytopathology.

INTRODUCTION: Unlike epithelial malignancies, mesenchymal neoplasms arising within the tubular gut are less often encountered in endoscopic ultrasound-guided (EUS) fine-needle aspiration biopsies (FNABs). Nonetheless, preoperative diagnosis of such neoplasms has important therapeutic and prognostic value. We report our experience with this category of neoplasms from the past decade. MATERIALS AND METHODS: We performed a 10-year retrospective search at our respective institutions to identify EUS-guided FNAB cases of mesenchymal neoplasms arising from the tubular gut wall and closely adjacent structures. Cytopathologic diagnoses were compared to corresponding surgical pathology (SP) when available. Cases with either no confirmatory cell block (CB) immunohistochemical (IHC) staining, or no SP were excluded. RESULTS: Two-hundred eighty-two cases (M:F = 1:1; age range: 25-94 years, mean age = 60 years) of EUS-guided FNAB from the tubular gut met our criteria. Onsite adequacy was performed on nearly all cases. Case numbers: 209 gastrointestinal stromal tumors (GIST), 58 smooth muscle neoplasms, and 15 miscellaneous neoplasms. Of these, 188 (67%) had SP follow-up. We found that 258 (91%) aspirates had a correct specific diagnosis, 3 (1%) were nondiagnostic, 18 (6%) had indeterminate diagnoses, and 3 (1%) had incorrect diagnoses (2 leiomyosarcomas mistaken as leiomyoma, and 1 fibrosclerotic lesion mistaken as inflammatory pseudotumor). Of 94 cases with no SP, all had a specific cytologic diagnosis based on confirmatory IHC staining from the CB including 61 GISTs, 29 smooth muscle neoplasms, and 4 miscellaneous tumors. CONCLUSION: This study endorses the clinical utility of EUS-guided FNAB in the diagnosis of tubular gut mesenchymal neoplasms. A definitive and accurate diagnosis is possible in over 90% of cases, chiefly when cytomorphology is coupled with optimal cellularity and IHC from a concurrent CB. EUS-guided FNAB diagnosis of mesenchymal tubular gut neoplasms may play an important role in determining neoadjuvant therapy as targeted therapy evolves.

Suspicious for Malignancy Diagnoses on Pleural Effusion Cytology.

OBJECTIVES: A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion. METHODS: A search for pleural effusions diagnosed as SFM (2008-2018) was performed. Patient records and pathology reports were reviewed. Specimens were subdivided into groups depending on volume (<75, 75-400, >400 mL). Diagnoses of malignant pleural effusion (MPE) served as controls. RESULTS: We identified 90 patients, with a mean age of 60.6 years. Diagnoses included suspicious for involvement by carcinoma/adenocarcinoma in 64.4%, leukemia/lymphoma in 15.6%, melanoma in 2.2%, sarcoma in 3.3%, germ cell tumor in 1.1%, and not otherwise specified in 13.3%. Immunostains were performed in 47.8% and considered inconclusive in 24%. Average sample volume was 419 mL. There was a statistically significant difference between the SFM vs MPE groups for volumes greater than 75 mL (P = .001, χ 2 test), with SFM having increased proportion of volumes  greater than 400 mL, compared with the MPE group. There was no statistically significant difference in mean overall survival when the groups were compared (P = .49). CONCLUSIONS: Samples with low cellularity, scant cell blocks, and inconclusive immunostains may contribute to a suspicious category diagnosis in pleural effusions.

Impact of the Current US Preventive Services Task Force Recommendations for Cervical Cancer Screening in Young Women 21 to 29 Years Old.

OBJECTIVES: In 2012, the US Preventive Services Task Force decreased the recommended frequency of cervical cytology screening to once every 3 years and recommended against testing women younger than 21 years regardless of sexual history. We evaluated the impact of this in 21 to 29-year-old women at a tertiary care academic medical center in 2011 and 2017. METHODS: We retrospectively analyzed Papanicolaou test results at two time points in 21- to 29-year-old women. RESULTS: There was a decrease in the number of high-grade lesions in 21- to 25-year-old women (odds ratio [OR], 0.36) from 2011 to 2017. Within the 26- to 29-year-old patient group, there was a trend toward a higher percentage of high-grade squamous intraepithelial lesion (HSIL) in 2017 compared to 2011 on cytology, which did not reach statistical significance (OR, 1.46). However, follow-up histologic specimens showed a higher percentage of HSIL in 2017 compared to 2011 in this age group (OR, 2.16). CONCLUSIONS: Our findings suggest that the cervical cancer screening guidelines introduced in 2012 have not had a detrimental impact on the outcomes of cervical cancer screening for 21- to 25-year-old women. However, we need to continue monitoring the effects of decreased screening in 26- to 29-year-old women.

Molecular Alterations in Pulmonary Adenocarcinoma of African Americans.

OBJECTIVES: Identify molecular alterations in pulmonary adenocarcinoma (ADC) in African American (AA) patients diagnosed on cytology specimens. METHODS: After institutional review board approval, we searched our database from 2013 to 2017 for AA patients with a diagnosis of pulmonary ADC. Molecular and clinical data were reviewed. White patients also diagnosed with pulmonary ADC on cytology samples formed a control group. RESULTS: A total of 113 patients were identified. Mean age was 63.4 years. Molecular tests were available for 91 patients. Mutations were identified in 53 (58.2%) cases. The most common mutations were EGFR (n = 19 cases, 36%) and KRAS (n = 24 cases, 45%). When compared with whites, AA patients were diagnosed at higher stages (P = .045) and demonstrated shorter overall survival (17 vs 47 months, P = .0150). No differences were noted regarding distribution of molecular alterations. CONCLUSION: AA patients have similar molecular alterations in ADCs as their white counterparts. However, they have worse outcomes.

Risk of malignancy associated with cytomorphology subtypes in the salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System: A bi-institutional study.

BACKGROUND: Salivary gland neoplasm of uncertain malignant potential (SUMP) is a diagnostic category in the Milan System for Reporting Salivary Gland Cytopathology. The objective of this study was to assess the risk of neoplasm (RON) and the risk of malignancy (ROM) in SUMP cases by evaluating them based on their prominent cytomorphology. METHODS: The pathology databases were searched for cases of fine-needle aspiration-diagnosed SUMP at The Johns Hopkins Hospital and Northwestern University from 2013 to 2018. Only cytopathology cases diagnosed as SUMP that had available surgical follow-up were included. RESULTS: Sixty-five patients with SUMP were identified, including 31 men and 34 women who ranged in age from 15 to 87 years (mean age, 55.2 years). Sixty-five cases had histologic follow-up, including 13 (20%) with basaloid features, 13 (20%) with oncocytic features, and 39 (60%) with unspecified features. No cases with clear cell features were found. Overall, the RON in the SUMP category was 95.4% (62 of 65 cases), and the ROM was 33.8% (22 of 65 cases). The RON in SUMPs with basaloid, oncocytic, and unspecified subtypes was 92.3%, 100%, and 94.9%, respectively, whereas the ROM was 38.5%, 7.7%, and 41%, respectively. The most common benign neoplasm was pleomorphic adenoma (23.1%), whereas mucoepidermoid carcinoma (9.2%) was the most common malignant neoplasm. CONCLUSIONS: This study shows that the ROM differs significantly based on cytomorphology subtypes, whereas the overall ROM is approximately the same as the target rate in the Milan System for Reporting Salivary Gland Cytopathology. Moreover, the RON remains high in the SUMP category among different cytomorphology subtypes. Adequate sampling, immunohistochemical staining, and familiarity with metaplastic and reactive changes may improve the diagnosis.

Temporal bone involvement of IgG4-related disease: a rare condition misleading to petrous apicitis causing lateral rectus palsy.

IgG4-related disease (IgG4-RD) of temporal bone is rare and clinical manifestation mimics infection. A 19-year-old female presented with progressive left earache and intermittent left nasal obstruction. Then, she rapidly developed left lateral rectus palsy. The physical examination revealed mild redness of left tympanic membrane and a small nasal polyp from the left middle meatus. CT scan showed left petrous apicitis and enhancing sinonasal mucosa. Therefore, Gradenigo's syndrome was first considered. The empirical intravenous antibiotic was immediately prescribed and surgery was performed. The intraoperative pale soft tissue mass in middle ear and polyp in the left nasal cavity were sent for pathological examination and found positive immunohistochemical stains for IgG4 in plasma cells. Systemic corticosteroid, the first-line treatment, was started and her symptoms were finally recovery.

Insulinoma-associated protein 1 immunostaining on cytology specimens: an institutional experience.

Neuroendocrine tumors (NETs) are epithelial neoplasms with prominent neuroendocrine differentiation. Cytologic examination and utilization of immunohistochemical (IHC) markers are important diagnostic tools for the evaluation of these tumors. Herein we report our experience with the application of INSM1 in cytology samples. We searched our pathology system for cytologic specimens with INSM1 IHC performed from 2017 to 2018. Patients' demographics were recorded, and cytology materials were reviewed including all neuroendocrine IHC markers performed. A total of 134 (67 male, 67 female) specimens with INSM1 IHC were identified. Specimens included 91 (68.2%) NETs or tumors with neuroendocrine features (TNEFs), 33 (24.3%) nonneuroendocrine lesions (non-NET), and 10 (7.5%) nonneoplastic diagnoses. INSM1 was positive in 90 (99%) of the NET/TNEFs and negative in 32 (97%) non-NETs. CD56 was positive in 42 (95.5%) of the NET/TNEFs and negative on 9 (69.2%) of the non-NETs. The sensitivity of INSM1 was 99% and specificity was 97%, whereas the sensitivity of CD56 was 95.5% and specificity was 69.2%. Chromogranin had the lowest sensitivity (82.5%), and synaptophysin had the lowest specificity (66.7%). Both positive and negative predictive values of INSM1 were higher than CD56 (99% versus 91.3% and 97% versus 81.8%, respectively). INSM1 is a sensitive and specific marker for detection of NETs in cytology samples independent of primary site.

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients' Demographics.

BACKGROUND: We report our experience with malignant pleural effusion (MPE) and the impact of patients' demographics on the differential diagnosis at the primary site. METHODS: After IRB approval, we searched our pathology database from January 2013 to January 2017 for patients with positive pleural effusions (PEs). Patients' demographics and clinical histories were noted. RESULTS: 474 patients were identified (288 females [61%] and 186 males [39%]), ranging in age from 19 to 64 years old. Ethnicity was distributed as follows: Caucasian (n = 330, 70%), African American (n = 114, 24%) and Asian (n = 30, 6%). The most common primary sites were the lung (n = 180, 37%), followed by the breast (n = 81, 17%), and the gynecologic system (67, 13%). The lung was the most common primary for all ethnicities (n = 190, 40%). The second-most common primary site was the breast in African Americans and Caucasians and upper gastrointestinal (GI) tract in Asians. In 5 cases (1%), the primary tumor could not be determined. CONCLUSION: Cytology examination is a useful method to diagnose primary sites of PE. Pulmonary primary is the most common cause of effusion in all ethnicities. In African American and Caucasian patients, the breast was the second-most common site of MPE, while in Asian patients it was the upper GI tract.

Molecular genetic alterations in thyroid transcription factor 1-negative lung adenocarcinoma in cytology specimens: A subset with aggressive behavior and a poor prognosis.

BACKGROUND: Patients with thyroid transcription factor 1 (TTF1)-negative pulmonary adenocarcinoma (ADC) have been reported to have a worse prognosis and to lack epidermal growth factor receptor (EGFR) mutations. This study describes a series of cytology specimens from patients with clinically confirmed pulmonary carcinoma negative for TTF1. METHODS: A search for TTF1-negative ADC from 2010 to 2017 was performed. Each patient's clinical history, pathology specimens, and molecular results were noted. Two hundred ten patients with TTF1-positive pulmonary ADC formed the control group. RESULTS: Fifty specimens were identified from 50 patients (26 females and 24 males). The median age was 58.5 years. The smoking history was as follows: 38 smokers/former smokers (76%), 10 nonsmokers (20%), and 2 patients with an unknown status (4%). Thirty-nine patients (78%) had no previous history of malignancy. The clinical stages were as follows: stage I or II (n = 2 [4%]), stage III (n = 9 [18%]), stage IV (n = 37 [74%]), and unknown (n = 2 [4%]). Patients' mean survival was 10.3 months. Molecular results were available in 43 cases. Twenty-seven cases (63%) had no mutation identified; when they were compared with the control group, TTF1-negative patients had overall shorter survival (P = .0047), even though no statistically significant difference was seen on the clinical stage. Known mutations were less frequent (P = .0095) in TTF-negative tumors (KRAS mutations, n = 11 [25%]; anaplastic lymphoma kinase [ALK], n = 3 [7%]; and EGFR, n = 2 [5%]). This was particularly true for EGFR mutations (P = .047). However, ALK rearrangements were present at an increased frequency in the TTF1-negative group (P = .018). CONCLUSIONS: Patients with TTF1-negative lung ADC have worse overall survival, a lower frequency of known mutations, and a higher frequency of ALK alterations.

Insulinoma-Associated Protein 1 Immunostain: A Diagnostic Tool for Pulmonary Small Cell Carcinoma in Cytology.

OBJECTIVE: Cytology plays an important role in the diagnosis of small cell carcinoma (SCLC). Application of immunohistochemical (IHC) markers improves the accuracy and reproducibility of the diagnosis of SCLC. We report the application of insulinoma-associated protein 1 (INSM1) in the diagnosis of SCLC in cytology samples. METHODS: Our pathology data system was searched for SCLC where INSM1 IHC was performed. Patients' demographics were recorded. Cytopathology specimens were reviewed. RESULTS: A total of 32 cases were identified. INSM1 was positive in 31 (97%) cases. Twenty-seven cases showed a strong/diffuse pattern (84%). Four cases were focally/weak positive (13%). One case was negative (3%). the sensitivity of INSM1 for recognition of SCLC was 97%. CD56 was performed in SCLC. Twenty cases were strongly/diffusely positive (87%). One case was negative (4%). The sensitivity was 96%. CONCLUSION: INSM1 is positive in the majority of SCLC on cytology specimens and its sensitivity is similar to that of CD56 on SCLC. This has practical implications for the diagnosis of these tumors in cytology samples.