Diagnostic effectiveness of [18F]Fluoroestradiol PET/CT in oestrogen receptor-positive breast cancer: the key role of histopathology. Evidence from an international multicentre prospective study.

INTRODUCTION: [18F]Fluoroestradiol ([18F]FES) PET/CT has been proposed as a tool for detecting the oestrogen receptor density in patients with metastatic breast cancer (BC) non-invasively across all disease localizations. However, its diagnostic potential in terms of the detection rate (DR) of metastases is unclear. In this study, we pitted this method against [18F]FDG PET/CT and tried to identify predictors of the diagnostic superiority of the [18F] FES-based method. MATERIALS AND METHODS: From a multicentre database, we enrolled all patients with metastatic BC who had undergone both [18F]FES PET/CT and [18F]FDG PET/CT. Two readers assessed both images independently and used a patient-based (PBA) and lesion-based analysis (LBA) to calculate the DR. Pathology-related and clinical factors were tested as predictors of [18F]FES PET/CT superiority using a multivariate model. RESULTS: 92 patients, bearing a total of 2678 metastases, were enrolled. On PBA, the DR of [18F]FDG and [18F]FES PET/CT was 97% and 86%, respectively (p = 0.018). On LBA, the [18F]FES method proved more sensitive than [18F]FDG PET/CT in lymph nodes, bone, lung and soft tissue (p < 0.01). This greater sensitivity was associated with lobular histology, both on PBA (Odds Ratio (OR) 3.4, 95%CI 1.0-12.3) and on LBA (OR 4.4, 95%CI 1.2-16.1 for lymph node metastases and OR 3.29, 95%CI 1.1-10.2 for bone localizations). CONCLUSIONS: The overall DR of [18F]FES PET/CT appears to be lower than that of [18F]FDG PET/CT on PBA. However, the [18F]FES method, if positive, can identify more lesions than [18F]FDG at most sites. The higher sensitivity of [18F]FES PET/CT was associated with lobular histology.

Clinicopathologic and Dermoscopic Features of 20 Cases of Spark's Nevus, a Dermoscopic Simulator of Melanoma.

ABSTRACT: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma.

Dedicated neck 18 F-FDG PET/CT: An additional tool for risk assessment in thyroid nodules at ultrasound intermediate risk.

BACKGROUND: Several ultrasound (US) risk stratification systems have been proposed for the assessment of thyroid nodules, and their performance was shown as good. However, the rate of nodules assessed at intermediate risk is not negligible and whether they should be submitted or not to further examination is still under debate. The present study aimed to evaluate the reliability of 18 F-FDG PET/CT in stratifying the risk of malignancy in these lesions. METHODS: Two institutions participated to this retrospective study in which a dedicated 18 F-FDG PET/CT was proposed to patients having a thyroid nodule with US assessment of EU-TIRADS 4 or 5. 18 F-FDG PET/CT did not influence the diagnostic and therapeutic decision. Histology was the gold standard for all patients. RESULTS: Ninety-three patients were included for the study with 48 EU-TIRADS 4 and 45 EU-TIRADS 5 nodules. Of these, 26 underwent thyroidectomy following FNAC suspicious for or consistent with malignancy, 38 for inconclusive cytology, 27 because of large goitre and 2 for high-risk lesion at US. At histology, 35 carcinomas and 58 benign lesions were found. Cancer prevalence was 16.7% in EU-TIRADS 4 and 60% in EU-TIRADS 5. Overall, 18 F-FDG PET/CT was positive in 33/35 cancers (94.5% sensitivity) and negative in 31/58 benign lesions (53.4% specificity). When considering only EU-TIRADS 4, 18 F-FDG PET/CT was positive in 7/8 cancers and negative in 20/40 benign lesions; among these, there were 36 cases with FNAC indication according to dimensional cut-off (ie >1.5 cm), and 18 F-FDG PET/CT showed 85.7% sensitivity and 41.4% specificity. CONCLUSIONS: 18 F-FDG PET/CT may have a role in stratifying the cancer risk of thyroid nodules with an intermediate ultrasound assessment. More specifically, thyroid lesions classified as EU-TIRADS 4 and with no 18 F-FDG uptake could be ruled out from further examination, similar to other anamnestic and clinical suspicious factors of patients. Further prospective and cost-effectiveness studies are needed.

Chronic diseases, medical history and familial cancer, and risk of leukemia and non-Hodgkin's lymphoma in an adult population: a case-control study.

PURPOSE: This investigation was aimed at evaluating the association between chronic diseases, medical history and familial cancer, and the risk of developing hematological malignancies. METHODS: Data were drawn from a population-based case-control study carried out to assess the risk of non-Hodgkin's lymphoma and leukemia in an adult population exposed to environmental air pollution in Northern Italy. Each case was classified according to the WHO ICD-O-3 classification. Statistical analyses were performed by multivariable unconditional logistic regression in 573 interviewed subjects (199 lymphoid cases, 95 myeloid cases, and 279 healthy controls). RESULTS: Lymphoid malignancies were associated with a history of gastroduodenal ulcer (OR 2.1, 95 % CI 1.2-3.6), rheumatoid arthritis (OR 4.4, 95 % CI 1.3-19.0), anemia (OR 3.3, 95 % CI 1.2-9.3), cholecystectomy (OR 2.9, 95 % CI 1.0-8.0), heavy diagnostic X-ray exposure (OR 2.1, 95 % CI 1.3-3.7), and a familial risk of non-Hodgkin's lymphoma (OR 10.1, 95 % CI 1.3-458). Myeloid malignancies were associated with non-neoplastic thyroid diseases (OR 6.2, 95 % CI 1.7-35.6) and anemia (OR 6.8, 95 % CI 2.0-23.1). Subgroup analysis highlighted an excess risk of MALT in patients with gastroduodenal ulcer (OR 5.3, 95 % CI 1.04-23.7) and of AML in patients with rheumatoid arthritis (OR 6.9, 95 % CI 1.2-38.1), and of MDS in subjects exposed to heavy diagnostic X-ray (OR 3.4, 95 % CI 1.03-11.2) when the analysis was restricted to irradiation of pelvis, abdomen, or thorax. CONCLUSIONS: Most observed associations confirm results from previous studies. The higher risk of lymphoid malignancies among patients with a history of cholecystectomy needs further investigations.

Blastic plasmacytoid dendritic cell neoplasm: a short review and update.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic neoplasm (less than 1% of primary cutaneous lymphomas and acute leukemia) with a highly aggressive clinical course and frequent skin, bone marrow and central nervous system involvement. Even though there is often an early response to chemotherapy, leukemic dissemination relapses are very common and result in poor outcomes, with a median overall survival of 8 to 14 months in the first-line setting using standard combination chemotherapy regimens. Almost 90% of patients experience skin involvement as their initial site of infection, where BPDCN may stay restricted for weeks or even months until a swift secondary phase involving multiple organs takes place. Consequently, it is crucial to suspect and identify early skin lesions, as well as to conduct and report a skin biopsy as soon as possible. In order to diagnose and treat BPDCN, a multidisciplinary strategy involving collaboration between pathologists, hematologists, and dermatologists is unquestionably essential.

Ultrasound-guided core-needle biopsy of extra-ocular orbital lesions.

OBJECTIVE: To evaluate the diagnostic yield of ultrasound-guided core-needle biopsy of extra-ocular orbital lesions. METHODS: Fifty-five patients with monolateral exophthalmos prospectively underwent computed tomography (CT) to investigate the presence of an extra-ocular mass (n = 25). Excluding benign lesions (n = 7) and patients in whom CT revealed an unknown primitive malignancy (n = 5), 13 patients (7 male, 6 female; mean age 62 ± 16 years) underwent ultrasound. Lesion appearance (echotexture, power Doppler vascularisation), size, position with respect to the cone and to the globe were recorded. Ultrasound-guided biopsies were performed (automatic, n = 9; semi-automatic 18-G needle, n = 4). Sample adequacy and complication rate were recorded. RESULTS: Ultrasound demonstrated hypoechoic lesions with mild power Doppler vascularity, that were completely (n = 7) or partially extra-conal (n = 6), located laterally (n = 8) or posteriorly (n = 5) to the globe. Mean size was 3.25 cm. All biopsies yielded adequate material for histological and immunohistochemical analysis (nine non-Hodgkin's lymphomas, two adenocarcinomas, one lymphoid hyperplasia, one inflammatory pseudotumour). Complications included cutaneous eyelid haematoma (n = 3) and retro-bulbar haematoma (n = 1), treated conservatively and resolved at 10-day follow-up. No immediate or delayed vision reduction was reported. CONCLUSIONS: Ultrasound-guided core-needle biopsy of extra-ocular orbital lesions is feasible and accurate, being free from long-term complications. This procedure provided 100 % adequate samples to achieve final diagnosis. KEY POINTS: • Ultrasound-guided core-needle biopsy of extra-ocular orbital lesions seems feasible and accurate. • In this series it provided a final diagnosis in 13/13 cases. • It appears free from long-term complications. • It provides immunohistochemical analysis of the specimen. • It should represent a valuable alternative to surgical biopsy.

Two cases of granuloma faciale showing rosettes.

Granuloma faciale (GF) is a rare benign chronic inflammatory dermatosis often difficult to distinguish clinically from other diseases, both inflammatory and neoplastic. Dermoscopy can be a helpful diagnostic tool and indeed several dermoscopic criteria observed in GF have been described in literature. We present two patients affected by GF in which we have observed rosettes.

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Cervical, oral and anal Human papillomavirus infection in women attending the Dermatology Unit of a regional reference hospital in Genoa, Italy: a prevalence study.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. In women with genital infection, the virus can be transmitted by sex to the oral cavity of their partners and then to their own oral cavity. The aim of the present study was to establish the prevalence of cervical/anal/oral HPV infection in women attending the Dermatology Unit of the Policlinico San Martino of Genoa, the regional reference hospital in Liguria, Italy. Methods: Between January 2016 and December 2018, the female patients attending the STI center (cases) and those requiring a full body skin examination for skin cancer screening ("supposed" healthy population: controls) were recruited. Cervical/anal/oral samples were collected with ThinPrep liquid based cytology preparation system: polymerase chain reaction for HPV and cytological evaluation were performed. Overall, 85 cases and 31 controls were recruited. Results: Cervical HPV infection was detected in 60% of the cases and 48% of the controls; anal HPV infection in 44% of the cases and 26% of the controls. Cervical and anal HPV infection resulted associated, especially in the control group. Moreover, 32% of the cases and 29% of the controls proved HPV positive in the oral cavity. In the cases of our series, prevalence of cervical, anal and oral HPV infection was higher compared with the controls. Conclusions: The high prevalence of anal-oral infections and the frequent association between anal and cervical infections, provide reason to suggest HPV screening also in the anal and oral regions, which may represent HPV reservoirs and grounds for cancer development.

A Collision Intrathyroidal Tumor Causing Primary Hyperparathyroidism: Evidence From an 18F-Choline PET/CT Study.

ABSTRACT: A 67-year-old man was diagnosed with primary hyperparathyroidism and normofunctioning left nodular goiter. Fine-needle aspiration cytology showed thyroid (Thy) 4 (suspicious of malignancy). After first-line imaging proved negative, integrated 18F-choline PET/4D contrast-enhanced CT revealed uptake by the thyroid nodule and by 3 nodules of the left central compartment. Thyroidectomy and lymphadenectomy were performed. Histopathology revealed a collision tumor (ie, 2 histologically distinct tumors occurring at the same anatomic site) composed of both PTC (papillary thyroid carcinoma) and parathyroid carcinoma within the left thyroid nodule. Lymph nodes showed PTC metastases. Primary hyperparathyroidism and calcium levels normalized, and the patient underwent radioiodine therapy.

Dermoscopic Criteria, Histopathological Correlates and Genetic Findings of Thin Melanoma on Non-Volar Skin.

Dermoscopy is a non-invasive, in vivo technique that allows the visualization of subsurface skin structures in the epidermis, at the dermoepidermal junction, and in the upper dermis. Dermoscopy brought a new dimension in evaluating melanocytic skin neoplasms (MSN) also representing a link between clinical and pathologic examination of any MSN. However, histopathology remains the gold standard in diagnosing MSN. Dermoscopic-pathologic correlation enhances the level of quality of MSN diagnosis and increases the level of confidence of pathologists. Melanoma is one of the most genetically predisposed among all cancers in humans. The genetic landscape of melanoma has been described in the last years but is still a field in continuous evolution. Melanoma genetic markers play a role not only in melanoma susceptibility, initiation, and progression but also in prognosis and therapeutic decisions. Several studies described the dermoscopic specific criteria and predictors for melanoma and their histopathologic correlates, but only a few studies investigated the correlation among dermoscopy, pathology, and genetic of MSN. The aim of this work is to review the published data about dermoscopic features of melanoma, their histopathological correlates with regards also to genetic alterations. Particularly, this review will focus on low-CSD (cumulative sun damage) melanoma or superficial spreading melanoma, high-CSD melanoma, and nevus-associated melanoma.

Mycobacterium kansasii infection in a psoriasis patient treated with adalimumab and switch to apremilast: First report and literature review.

Patient under anti-TNF-alpha treatment have an increased risk of mycobacterial infections, particularly tuberculosis. Only four case reports of Mycobacterium kansasii infection under anti-TNF-α treatment (two with etanercept, two with infliximab) have been reported, but none under adalimumab. A 72-year-old man treated with adalimumab for psoriasis vulgaris and arthropathic psoriasis, complained on nocturnal cough, occasional hemoptysis and the new onset of ill-defined, reddish, asymptomatic persistent plaques-nodules covered by serum crusts on his back, on the dorsum of the right hand and right middle finger. Routine laboratory investigations, HIV and TB screening (QuantiFERON-TB-Gold test) were all within normal limits. A skin biopsy was inconclusive and special staining resulted negative for microorganisms. Only PCR identified M. kansasii. The patient stopped adalimumab and started anti-TB treatment with gradual improvement of the skin lesions. At 26 months follow-up visit no signs or symptoms of relapse of M. kansasii disease occurred.

Unstimulated Serum Thyroglobulin Levels after Thyroidectomy and Radioiodine Therapy for Intermediate-Risk Thyroid Cancer Are Not Always a Reliable Marker of Lymph Node Recurrence: Case Report and a Lesson for Clinicians.

Over 50% of patients with papillary thyroid carcinoma (PTC) have cervical lymph-node metastasis on diagnosis, and up to 30% show nodal recurrence after surgery plus radioactive iodine (131I) (RAI) therapy. The combination of ultrasonography (US) and fine-needle aspiration cytology (FNAC) and the measurement of thyroglobulin (Tg) in washout fluid are cornerstones in the diagnosis of nodal metastasis. In the absence of anti-Tg antibodies, unstimulated serum thyroglobulin (Tg) levels are generally a reliable marker of recurrent disease, and 18F-FDG positron emission tomography (PET)/computed tomography (CT) plays an important role in the imaging work-up. We report the case of a 65-year-old man evaluated for a large multinodular goitre which caused compressive symptoms; the dominant nodule in the left lobe presented suspicious features on US. Thyroid function showed subclinical hypothyroidism, calcitonin was normal, serum thyroglobulin levels were low, and anti-thyroid antibodies were absent. The prevalent left nodule showed an intense uptake on 18F-FDG PET/CT but proved benign at FNAC. On the basis of the suspicious clinical and imaging features, total thyroidectomy was performed. Histology revealed a tall-cell variant of PTC with scattered expression of Tg and diffuse high expression of cytokeratin (CK) 19; RAI therapy was performed. Within 6 years of surgery, left laterocervical lymph-node recurrence was twice detected (first at levels II and III, then at levels IV and VI) by US and 18F-FDG-PET/CT and was confirmed by FNAC. Tg levels in the washout fluid proved clearly diagnostic of metastasis only in the second, larger, recurrence, whereas serum Tg levels (in the absence of anti-Tg antibodies) always remained undetectable on L-thyroxine therapy. Surgery was performed on both recurrences, and histology confirmed lymph-node metastasis of PTC. Immunohistochemical expression of Tg and CK 19 was similar to that of the primary tumour. No further relapses have occurred to date. Posttherapy (surgery and RAI) unstimulated serum Tg levels may not be a reliable marker of nodal recurrence in patients with differentiated thyroid cancer (DTC) that produces low amounts of Tg.

Indeterminate thyroid nodules. The role of 18F-FDG PET/CT in the "era" of ultrasonography risk stratification systems and new thyroid cytology classifications.

PURPOSE: To evaluate the reliability of 18F-FDG PET/CT in distinguishing differentiated thyroid cancers (DTCs) and follicular neoplasms (FNs) from nodular hyperplasias (NH) in thyroid nodules with indeterminate cytology according to the Italian consensus for the classification and reporting of thyroid cytology (ICCRTC). We also tested whether the 18F-FDG PET/CT result was an independent risk factor for DTCs or FNs when sex, age, nodule dimensions, the European Thyroid Imaging and Reporting Data System (EU-TIRADS) and ICCRTC were considered. METHODS: We evaluated all patients with thyroid nodules and indeterminate cytology from September 2015 to May 2019; nodules were classified as low risk (TIR3A) and high risk (TIR3B) according to the ICCRTC. Neck ultrasonography features according to EU-TIRADS were re-evaluated and 18F-FDG PET/CT performed. All these patients were surgically treated. RESULTS: We included 111 patients; 67 nodules were classified as TIR3A and 44 as TIR3B. Overall, we found 27 DTCs, 57 NHs and 27 FNs. Among 73 FDG-negative nodules, we found four low-risk papillary thyroid cancers. All follicular thyroid cancers were identified by 18F-FDG-PET/CT. All TIR3A with low-risk US and negative 18F-FDG-PET/CT were NH. In TIR3A nodules, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of 18F-FDG PET/CT and EU-TIRADS for DTCs were 77.8%, 41.4%, 92.3%, 17.1% and 66.7%, 56.9%, 91.7%, 19.4%, respectively. In TIR3B nodules, the sensitivity, specificity, NPV and PPV of 18F-FDG PET/CT and EU-TIRADS for DTCs were 88.9%, 38.5%, 83.3%, 50% and 88.2%, 58.3%, 87.5%, 60%, respectively. On multivariate analysis, 18F-FDG-PET/CT (OR 9.04), ICCRTC (O.R. 7.57) and EU-TIRADS (OR 4.41) were all independent risk factors associated to DTCs and FNs. CONCLUSION: 18F-FDG-PET/CT is a reliable rule-out test for DTC even in thyroid nodules with indeterminate high-risk results. In this subgroup, PPV also tends to be considerable. 18F-FDG-PET/CT results, ICCRTC and EU-TIRADS proved independent risk factors associated to DTCs and FNs.