Julie McCarthy

False negatives in thyroid cytology: Impact of large nodule size and follicular variant of papillary carcinoma

Fine‐needle aspiration (FNA) cytology is well established in the diagnosis of thyroid nodules. However, false‐negative rates for malignancy of 3% to 10% are reported. The purpose of the present study was to investigate the impact of nodule size and follicular variant of papillary carcinoma (FVPTC) on false‐negative FNA rates in thyroid nodules and on malignancy rates in nodules with indeterminate cytology.

Follicular Variant of Papillary Thyroid Carcinoma: Differences From Conventional Disease in Cytologic Findings and High-Risk Features

IMPORTANCEnThe follicular variant (FV) of papillary thyroid carcinoma (PTC) is an important subtype that can be difficult to diagnose using preoperative cytologic analysis.nnnOBJECTIVEnTo compare conventional and FV PTC with regard to preoperative cytologic diagnosis using a tiered thyroid cytologic reporting system, tumor size at diagnosis, presence of invasion, and implications on prognostic scores.nnnDESIGN, SETTING, AND PARTICIPANTSnThis retrospective study was conducted in an academic teaching hospital and included 99 patients with conventional (nu2009=u200965) or FV (nu2009=u200934) PTC.nnnINTERVENTIONSnPreoperative thyroid cytologic findings, originally reported using the tiered British Thy system, were recategorized according to the Bethesda classification system. Pathologic features recorded included tumor size, presence of extrathyroid extension (ETE), and metastases. Prognostic scores were calculated according to the MACIS system.nnnMAIN OUTCOMES AND MEASURESnDifferences in patient demographics, preoperative cytologic findings, tumor pathologic features, and prognostic risk categories between conventional and FV PTC were studied.nnnRESULTSnThere were no differences in patient age or sex. Cytologic findings from FV PTC were significantly more likely to be reported in a lower-risk category than those from conventional PTC for (1) malignant vs lower-risk category (22 [56%] vs 2 [8%]); (2) suspected malignant or malignant vs lower-risk category (26 [66%] vs 6 [23%]); and (3) follicular neoplasm or higher-risk category vs lower-risk category (34 [87%] vs 10 [38%]) (Pu2009<u2009.001 for all 3 comparisons). There was also a significantly higher likelihood of false-negative cytologic findings among FV PTC cases (5 [19%] vs 1 [3%]) (Pu2009=u2009.03). The mean size of FV PTC lesions (25.9 mm) at the time of pathologic diagnosis was significantly greater than that of conventional PTC lesions (15.5 mm) (Pu2009=u2009.02). Even after exclusion of coincidental carcinomas, FV PTC tumors were significantly larger than conventional PTC tumors (31.7 vs 22.4 mm; Pu2009=u2009.03). In contrast, FV PTC was significantly less likely to show ETE (0 of 34 vs 10 of 65; Pu2009=u2009.01). There were no significant differences between FV PTC and conventional PTC in proportion of patients in intermediate- and high-risk prognostic groups combined (21 [62%] vs 38 [58%]) (Pu2009=u2009.83) or in mean MACIS scores (4.68 and 4.38, respectively; Pu2009=u2009.18).nnnCONCLUSIONS AND RELEVANCEnPreoperative cytologic findings from FV PTC were more likely than those from conventional PTC to indicate a lower risk category, and FV PTC tumors were larger at time of diagnosis. On the other hand, owing to a lower incidence of ETE in conventional PTC, there was no difference in prognostic score at diagnosis.

Outcome of Subclassification of Indeterminate (Thy-3) Thyroid Cytology into Thy-3a and Thy-3f

Objectives: The British Thy system is a widely used classification system for reporting thyroid fine-needle aspiration (FNA) cytology. The Royal College of Pathologists in 2009 recommended the subdivision of the Thy-3 (indeterminate) category into Thy-3a (atypia) and Thy-3f (follicular neoplasm). Our objective was to examine the malignancy rates of Thy-3a and Thy-3f cases at our institution and to investigate whether the risk of malignancy in Thy-3a cases is reduced by FNA on a different occasion showing benign cytology. Methods: This is a retrospective study of 748 thyroid nodules undergoing 1,032 FNAs, with indeterminate (Thy-3) cytology subdivided into Thy-3a and Thy-3f. Cases were correlated with final histology in surgical cases. Incidental carcinomas occurring outside the biopsied nodule were discounted. Results: A total of 109 nodules had a final cytological diagnosis of Thy-3a, of which 67 underwent surgery, with an incidence of malignancy of 13.4% (9/67); 90 nodules had a final cytological diagnosis of Thy-3f, of which 84 underwent surgery, with an incidence of malignancy of 17.9% (15/84). The difference in malignancy rates was not significant (p = 0.51). The incidence of malignancy in nodules with benign and Thy-3a cytology on separate occasions was not significantly different from cases with a single Thy-3a cytology. Conclusions: Thyroid nodules with Thy-3a cytology have a slightly lower risk of malignancy than Thy-3f cases. However, the difference is not significant and does not appear to be reduced by FNA on a separate occasion showing benign cytology. Management decisions for patients with Thy-3a cytology should be taken carefully to avoid missing cancers.

Impact of Microcalcifications on Risk of Malignancy in Thyroid Nodules with Indeterminate or Benign Cytology

Objective Adverse sonographic features such as microcalcification may predict increased likelihood of malignant cytology by fine-needle aspiration and, accordingly, increased risk of malignant histology. Our objective was to study the predictive value of microcalcifications and other sonographic features for malignancy among thyroid nodules with benign or indeterminate cytology. Study Design Case series with chart review. Setting Academic teaching hospital. Subjects Patients (N = 769) with 858 thyroid nodules undergoing 1142 ultrasound fine-needle aspirations; 411 cases had surgical correlation. Methods Sonographic features predictive of malignancy were correlated with malignancy as determined by histology. Incidental malignancies occurring outside the index nodule were discounted. Results Cytology was inadequate (87 cases), benign (518), indeterminate (210), and malignant (44). In 32 cases, initial benign cytology was upgraded to a higher-risk category after repeat ultrasound fine-needle aspiration. Microcalcification (P = .001) and irregular margins (P = .04) were significantly predictive of malignant cytology. Among surgical cases, microcalcification (P < .001) and irregular margins (P = .04) were significantly predictive of malignant histology; 170 patients with initial benign cytology and 161 with indeterminate cytology underwent surgery. Microcalcification was significantly associated with malignancy among cases with indeterminate cytology (P = .04) but not among cases with benign cytology (P = .23); however, only 13 of 33 cases with benign cytology and microcalcifications underwent surgery. Conclusion Presence of microcalcification increases the risk of malignancy in thyroid nodules with indeterminate cytology and may thus aid in selection of cases for surgery.

A case of sarcoidosis in a patient with testicular cancer post stem cell transplant

A 20-year-old male was initially diagnosed with classical seminoma with para-aortic lymphadenopathy and pulmonary metastasis. Post-orchidectomy staging was T1 N2 M1a S1, good risk stage III disease with persistently elevated lactate dehydrogenase (LDH) and beta-human chorionic gonadotrophin ( β HCG), based on International Germ Cell Consensus Classifi cation Group (IGCCCG) classifi cation and was treated with four cycles of cisplatin and etoposide. β HCG level normalised after Cycle 2 but began rising after Cycle 3. Posttreatment computed tomography (CT)-scan showed new abdominal lymphadenopathy. The patient was deemed platinum refractory and was treated with two cycles of paclitaxel and infosfamide followed by three cycles of high-dose carboplatin and etoposide with growth factor support and stem cell rescue. Tumour markers normalised and there was no radiographic evidence of disease following salvage chemotherapy. A follow-up surveillance CT-scan fi ve years later showed newly-developed bulky mediastinal lymphadenopathy measuring up to 3 cm (Figure 1a and b). Tumour markers were all within normal range. Clinical assessment showed that patient continued to be free of focal and constitutional symptoms, with normal physical examination. After a presentation of the case at our multi-disciplinary team meeting it was felt that this new radiologic fi nding was suspicious of disease recurrence and an endoscopic transbronchial needle biopsy was recommended. Cytological evaluation revealed multiple non-caseating granulomata on a background of infl ammatory cells, with no evidence of malignant cells (Supplementary Figure 1a and b to be found online at http://www.informahealthcare. com/doi/abs/10.3109/0284186X.2012.689854 ). Serum angiotensin converting enzyme (ACE) level was 150U/l (normal range: 40 – 135U/l). These fi ndings were consistent with sarcoidosis. The patient was commenced on high dose oral prednisolone and after three months of tapering steroids a repeat CTscan showed complete resolution of his mediastinal lymphadenopathy (Figure 2a and b). Testicular tumour markers remain within normal limits. Germ cell tumours are considered a model for curable cancer, with excellent survival outcome. Up to 90% of seminoma falls into the good prognosis group at initial presentation, with fi ve-year survival over 90% [1]. However, survival of patients with relapsed disease after fi rst-line chemotherapy is less favourable. Platinum-refractoriness has been identifi ed as a poor prognostic indicator [2]. In relapsed seminoma, a response rate of up to 83% is seen with salvage chemotherapy with vinblastine, ifosfamide and cisplatin (VeIP), but only 54% maintain longterm survival [3]. High-dose chemotherapy with autologous stem cell support could potentially confer cure in the secondand third-line setting, with overall survival of 75% for relapsed pure seminomas [4]. Disease relapse after high-dose treatment is associated with a poor prognosis and the chance of prolonged remission is small, with response rates in the range of 18 – 36% [5,6]. Sarcoidosis is a multi-organ granulomatous disease of uncertain aetiology. It is proposed that the underlying aetiology is due to a T-helper cell-1mediated immune response to an unidentifi ed antigen in a genetically susceptible host [7]. The controversial link between sarcoidosis or sarcoid-like reactions and malignancy was fi rst made in the 1970s and linkage analysis has suggested an association in at least a quarter of all malignancies. This association is thought to be due to soluble antigenic factors shed by tumour cells or released by the tumour as a result of tumour necrosis. An increased incidence of sarcoidosis in patients with testicular cancer has been observed [8] at the time of and up to fi ve years after diagnosis

Herpetic tracheitis in association with rituximab therapy

A 58‐year old lady under active follow‐up with the respiratory services at our institution for bronchiectasis secondary to hypogammaglobulinaemia presented with hoarseness and haemoptysis. She was also receiving rituximab maintenance therapy for follicular lymphoma. Bronchoscopy demonstrated vesicular lesions on her vocal cords and trachea, confirmed as herpes simplex virus (HSV) on cytological analysis of brushings. She responded well to intravenous valacyclovir. Rituximab is increasingly utilised in the treatment of haematological and auto‐immune disorders. This case highlights the potential of this drug to potentiate susceptibility to infection in an already immunocompromised individual.

Seminoma and sarcoid: A confusing collision.

339 Background: In patients with active or prior malignancy, the presence of mediastinal lymphadenopathy is often assumed to indicate metastases. However, sarcoidosis can imitate malignancy on CT and PET imaging. The incidence of sarcoidosis or sarcoid-like reaction in cancer patients (especially testicular germ cell tumor patients) appears to be higher than in the general population.nnnMETHODSnWe report a series of 4 testicular cancer patients with mediastinal adenopathy mimicking metastatic disease. Subsequent investigations and follow-up revealed sarcoid-like reaction without active malignancy.nnnRESULTSnA 25 year old man presented with a neck swelling and was found to have left cervical adenopathy, mediastinal adenopathy and a right testicular mass. Biopsy of the cervical nodes revealed a mixed seminoma and non-seminomatous germ cell tumour. After 4 cycles of chemotherapy PET/CT revealed persistent hypermetabolic mediastinal adenopathy. Transbronchial needle aspirate (TBNA) revealed non-caseating granulomas (NCGs). After right orchiectomy and retroperitoneal lymph node dissection he remains in complete remission. A 26 year old man presented with scrotal swelling and investigations revealed bilateral testicular seminoma. CT revealed mediastinal adenopathy. TBNA revealed NCGs and he remains disease free after orchiectomy. A 42 year old man presented with right sided scrotal swelling. CT revealed mediastinal adenopathy. TBNA revealed NCGs. He was treated successfully with orchiectomy and chemotherapy for stage 1 seminoma. A 20 yr old man had mediastinal adenopathy on a surveillance CT 5 years after high dose chemotherapy and stem cell transplant for platinum-refractory seminoma. TBNA revealed NCGs and the adenopathy resolved with oral prednisone therapy.nnnCONCLUSIONSnSarcoid-like reaction in cancer patients may be due to an immunologic hypersensitivity to tumor-associated antigens. Although the precise pathogenesis is unknown, the clinical relevance of this phenomenon is clear. There is a need for histologic confirmation of suspected metastatic mediastinal adenopathy in patients with testicular cancer. We are collecting more cases in other malignancies and will present an update.