Survival predictors of radioiodine-refractory differentiated thyroid cancer treated with lenvatinib in the real-life.

CONTEXT: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. OBJECTIVE: To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. DESIGN: Multicenter, retrospective, cohort study. SETTING: Three Italian thyroid cancer referral centers. PARTECIPANTS: 55 RR-DTC treated with lenvatinib. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 (95% CI 19.06-32.93) and 70 months (95% CI 36-111.99), respectively. Pre-treatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS (p < 0.001; HR 18.82; 95% CI 3.65-97.08: score 0-1 as reference) and OS (p = 0.001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI)-avidity was independently related to PFS (p = 0.047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Post-treatment setting: best radiological response independently predicted PFS (p = 0.001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (p = 0.013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference). CONCLUSIONS: RR-DTC with good performance status and RAI-avid disease obtain the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor.

COVID-19 post-vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology.

COVID-19 vaccine-associated clinical lymphadenopathy (C19-LAP) and subclinical lymphadenopathy (SLDI), which are mainly detected by 18F-FDG PET-CT, have been observed after the introduction of RNA-based vaccines during the pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has been used to diagnose single cases or small series of SLDI and C19-LAP. In this review, clinical and LN-FNAC features of SLDI and C19-LAP are reported and compared to non-Covid (NC)-LAP. A search for studies on C19-LAP and SLDI histopathology and cytopathology was performed on PubMed and Google Scholar, on 11 January 2023. Reports on LN-FNAC of C19-LAP were retrieved. A total of 14 reports, plus one unpublished case of C19-LAP observed in our institution, diagnosed by LN-FNAC were included in a pooled analysis and compared to the corresponding histopathological reports. In total, 26 cases were included in this review, with a mean age of 50.5 years. Twenty-one lymphadenopathies assessed by LN-FNAC were diagnosed as benign, and three cases as atypical lymphoid hyperplasia; the latter were subsequently confirmed as benign (one by repetition of LN-FNAC, two by histological control). One case of mediastinal lymphadenopathy in a patient suffering from melanoma was reported as reactive granulomatous inflammation, while one unsuspected case was diagnosed as metastasis from melanoma. In all cases, the cytological diagnoses were confirmed by follow-up or excisional biopsy. The high diagnostic value of LN-FNAC in excluding malignant processes was extremely useful in this context and may be particularly valuable when CNB or histological excisions are difficult to perform, as was the case during Covid lockdowns.

Non-urothelial lesions of the urinary bladder A 14.5-year, single-institution review.

CONTEXT: In contrast to urothelial cancers, non-urothelial neoplasms involving the bladder are uncommon and often diagnostically challenging. These lesions include a variety of benign and malignant tumors often presenting with a combination of hematuria and the presence of a polypoid lesion at cystoscopy that may lead to an erroneous diagnosis of urothelial cancer. OBJECTIVE: We set out to quantify and classify the spectrum of non-urothelial lesions diagnosed in our institution, and briefly review the relevant literature on each lesion, with a focus on differential diagnosis and potential pitfalls. DESIGN: We performed a retrospective review (Jan 2008 - Jun 2022) of the cases diagnosed on TURB material at our institution. RESULTS: Out of 4071 TURB specimens, a total of 66 (1.62 %) non-urothelial lesions were identified. Most of these lesions were malignant (n = 51, 77 %), with metastases being the most common (n = 40, 60.6 %), followed by non-Hodgkin lymphoma (n = 8, 12 %). The remaining cases were benign lesions (n = 15, 22.7 %), with the most common being inflammatory myofibroblastic tumor (n = 4, 6.1 %) and endometriosis (n = 3, 4.5 %). CONCLUSIONS: In this retrospective case series, we identified various malignant and benign entities, some of which have been rarely reported in the bladder, such as paragangliomas, inflammatory myofibroblastic tumor, and leiomyosarcoma. These lesions may macroscopically and histologically mimic urothelial carcinoma. Because of their relative rarity and diagnostic overlap with conventional urothelial tumors, the pathologist should always keep in the mind the possibility of non-urothelial lesions.

A Rare Case of Castleman Disease Presenting as an Ovarian Tumor.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology. Its most common location is the mediastinum, but many other sites have been reported. We report a case of primary CD of the ovary, a rare localization with only 2 cases including the present case described in the world literature to date. A 58-yr-old woman who initially presented with abdominal pain underwent computed tomography scan which showed bilateral well-circumscribed solid adnexal masses. Because an ovarian bilateral tumor was suspected the patient was treated with a hysterectomy and bilateral salpingo-oophorectomy and the histopathologic examination confirmed the diagnosis of CD hyaline-vascular type of the right ovary associated with a contralateral fibroma. Three years after surgery the patient is alive and well and shows no signs of recurrent disease. The occurrence of this rare presentation of CD is the subject of this report. The problems of differential diagnosis with the most frequent lesions of the female pelvis are also discussed.

Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature.

Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT) scan of pelvis showed an enlarged uterus (20,0 × 12,0 cm) with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC) combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option.

The diagnostic accuracy of fine-needle cytology of Hurthle cell lesions; A comprehensive cytological, clinical and ultrasonographic experience.

BACKGROUND: Fine-needle cytology (FNC) diagnosis and pre-operative classification of Hurthle cells (HC) lesions may be difficult. Rapid on-site evaluation (ROSE) enhances the efficiency of FNC, mainly when utilized in close combination to clinical and ultrasound (US) data. OBJECTIVE: to describe an experience on HC FNC with contextual clinical,US and ROSE evaluation and assess if this comprehensive approach improves the FNC accuracy of HC lesions. METHODS: FNC of 112 HC lesion were diagnosed and classified, according to the Bethesda system, by clinical, US and ROSE in one year. All the cases were controlled by follow-up and histology when performed. RESULTS: Eighty-five cases were diagnosed HC rich goiter or Hashimoto thyroiditis and were classified THY2; 5 cases were diagnosed hyperplastic nodular goiter and classified THY3A. Eight cases were diagnosed suspect neoplasia and classified THY3B. Two cases were diagnosed suspect HC papillary thyroid carcinoma (PTC) and classified THY4 and 2 cases were diagnosed HC-PTC and classified THY5. THY3B, THY4, THY5 and 1 THY3A were histologically controlled. FNC were confirmed in 14 out of the 17 THY3-THY5 cases. CONCLUSIONS: A comprehensive diagnostic approach that include FNC, clinical data, US and ROSE improves the diagnosis and classification of HC lesions.

Oncocytic variant of mucoepidermoid carcinoma: a diagnostic challenge for the pathologist.

Oncocytic mucoepidermoid carcinoma of the salivary gland is rare. We report a 48-year-old man who presented with a slowly growing right parotid mass. A preoperative fine needle aspiration showed exclusively oncocytic cells and cellular debris. A first diagnosis of Warthin tumor or myoepithelioma was made. The patient underwent a superficial parotidectomy, and her postoperative course was uneventful. Histologically, the tumor was composed of solid nests and cystic gland containing clear mucoid material, lined predominantly with oncocytes and few mucous goblet cells. A final diagnosis of oncocytic variant of mucoepidermoid low-grade carcinoma was made. The recognition of this variant is important, because may be easy confused with most frequent benign tumor with oncocytic cells; in this case a complete surgical excision and long-term clinical follow-up are an adequate management.

Discordance rate of HER2 status in primary gastric carcinomas and synchronous lymph node metastases: a multicenter retrospective analysis.

BACKGROUND: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. MATERIALS AND METHODS: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. RESULTS: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. CONCLUSIONS: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.

Glomus tumor of uncertain malignant potential on the forehead.

Malignant glomus tumors (GTs) are rare, and diagnosis requires consideration of specific histologic criteria. Glomus tumors that do not fulfill the histologic criteria for malignancy but show at least 1 feature other than nuclear atypia should be classified as GTs of uncertain malignant potential (GTUMPs). We report the case of a 74-year-old man with a slowly progressing, painful, 2.5-cm nodule on the forehead that was successfully treated via wide surgical excision and was later diagnosed as a GTUMP. Three-year follow-up showed no local recurrence or distant metastasis. Malignant GTs and GTUMPs are rare, and the nomenclature and classification of these tumors is controversial. These findings and the difficulty of differential diagnosis in a continuum between benignity and malignancy prompted our report.

Cytological diagnosis of thyroid nodules in Hashimoto thyroiditis in elderly patients.

BACKGROUND: Long standing Hashimoto Thyroiditis (HT) causes shrinking and atrophy of the thyroid, but may also lead to diffuse enlargement of the gland and/or formation of nodules. These nodules should be differentiated from papillary thyroid carcinoma (PTC) and primary thyroidal non-Hodgkin lymphoma (PTL), which are possible complications of HT, and require pre-surgical diagnoses and different treatments. METHODS: Thirty-four elderly patients (≥ 65 yrs) with HT and diffuse or nodular enlargement of the thyroid underwent ultrasound (US)-guided FNC. Smears were routinely stained and evaluated; additional passes were used for flow cytometry (FC) assessment of lymphoid infiltrate in 6 cases. RESULTS: The cytological diagnosis was HT in 12 cases with prevalence of Hurtle cells in 2 cases, PTC in 1 case and PTL in 2 cases. FC assessed the reactive, non-lymphomatous nature of the lymphoid infiltrate in 5 cases and demonstrated light chain restriction, hence the lymphomatous nature of the lymphoid infiltrate in 2 cases of PTL. CONCLUSIONS: FNC plays a key role in the clinical surveillance and pre-surgical diagnosis of diffuse enlargement and nodular presentation of HT in elderly patients. FNC can correctly diagnose HT, PTC and PTL indicating the need for surgery and its extension in suspicious or neoplastic cases, leaving other cases to the medical treatment and clinical surveillance.

Cytological diagnosis of adult-type fibrosarcoma of the neck in an elderly patient. Report of one case and review of the literature.

BACKGROUND: Fibrosarcoma (FS) accounts for about 3% of all soft tissue sarcomas. It may arise in any area of the body, but it is relative rare in the head and neck district. Fine-needle cytology (FNC) is widely used in the diagnosis of neoplastic and non-neoplastic lesions of soft tissue. This article describes a case of FS of the neck diagnosed by FNC. METHODS: FNC was performed in a sub-fascial supraclavicular mass of an elderly patient under ultrasound (US) control. FNC was used to prepare cytological smears that were conventionally and immunocytochemically (ICC) stained. RESULTS: Smears showed a monomorphous spindle cell population and were positive at ICC for Vimentin and negative for CKAE1AE3, Actin, S-100, CD68, CT and PAX-8. The cytological diagnosis was confirmed by histological diagnosis. The patient underwent surgical resection and subsequent radiotherapy. CONCLUSIONS: FNC diagnosis of FS is reliable and accurate and may be conveniently used in the scheduling of surgical procedures, when needed, avoiding the treatment of benign nodules.

Early cytological diagnosis of extranodal stage I, primary thyroid Non-Hodgkin lymphoma in elderly patients. Report of two cases and review of the literature.

BACKGROUND: Primary thyroid lymphomas (PTLs) account for 5% of thyroid malignant tumors and often develop in patients with Hashimoto Thyroiditis (HT). Fine-needle cytology (FNC) is widely used in the diagnosis of thyroid nodules, including those arising in HT. Two PTL cases in HT elderly patients are here described and discussed. METHODS: FNC was performed in rapidly enlarged thyroid nodules of 2 elderly patients under ultrasound (US) control. FNC was used to prepare conventional cytologic smears, immunocytochemistry (ICC) and flow cytometry (FC) assessment of cell populations. RESULTS: The above cases were diagnosed as well differentiated, small B-cell and diffuse large B-cell thyroid lymphomas, respectively, by means of FNC. The histological diagnoses were mucosa-associated non Hodgkin lymphoma (MALT) and diffuse large B-cell lymphoma (DLBCL), confirming FNC diagnoses, and patients were treated accordingly. CONCLUSIONS: FNC diagnosis of PTL is reliable and accurate; it may be conveniently used in the clinical practice since it provides indications for appropriate therapeutic procedures or diagnostic surgery, and avoids to treat benign nodules.

[Sub-acute thyroiditis in a patient on immunosuppressive treatment]. / Tiroidite subacuta in un paziente in trattamento immunosoppressivo.

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

Spindle cell lipoma of the larynx.

Among the primary mesenchymal tumors of the hypopharynx and larynx, lipomas are rare. Macroscopically, they often resemble a retention cyst or laryngeal nodule. Spindle cell lipomas (SCLs) are an uncommon variant of lipoma. SCLs are extremely rare in the larynx; as far as we know, only 4 cases have been previously described in the literature. We present a new case of laryngeal SCL in a 65-year-old man who presented with a 1-year history of hoarseness, choking spells, stridor, and dyspnea. Examination revealed the presence of a large polyp on the left true vocal fold that had caused stenosis of the posterior glottis. The polyp was removed endoscopically, and the patient's stridor and dyspnea resolved. Histologically, the tumor was composed of bland, CD34-positive spindle cells with an abundant fibrous and myxoid stroma interspersed with mature fatty tissue. The patient was free of local recurrence at 2 years of follow-up.

Adrenal gland non-Hodgkin's lymphoma in a patient with pulmonary adenocarcinoma.

Although primary neoplasms of adrenal gland are uncommon, adrenal metastases are frequently encountered in patients with malignancy, and lung is the most common primary tumour site. Among primary tumours of the adrenal gland non-Hodgkin's lymphoma (NHL) is a very rare entity. We describe a case of a 79-year-old man with a previous diagnosis of adenocarcinoma of the lung who presented after 2 years with a unilateral adrenal gland mass. A solitary metastasis from pulmonary carcinoma was suspected and a laparoscopic adrenalectomy was performed. Histological examination revealed a diffuse large B-cell NHL. The patient was treated with CHOP regimen plus rituximab and a total remission was achieved. After an 8-month follow-up the patient was free of disease. This is the first reported case of a rare non-synchronous tumoral combination involving lung and adrenal gland, emphasising at the incidental discovery of the NHL during a procedure performed for a pulmonary adenocarcinoma.

Metastatic renal cell carcinoma to the thyroid gland 24 years after the primary tumour.

Among the metastases to thyroid gland, metastases from renal cell carcinoma (RCC) are not rare and their frequent macroscopic looks are similar to primary thyroid tumours. We report an unusual case of thyroid metastases from renal carcinoma in a 72 -year-old man presented with a 1-year history of choking spells, stridor and dyspnoea. Patient underwent right nephrectomy for RCC, 24 years ago. In the present case, a right hemithyroidectomy was performed for a suspected anaplastic thyroid carcinoma. Histological examination showed a metastases of a clear cell renal carcinoma. Although the RCC showed an indolent biological behaviour, the late thyroid metastases have concurred with a poor prognosis and the patient died 5 months after surgery. The interest of this case lies in the long progression-free survival of the RCC preceded by the diagnosis of the thyroid nodule and the discrepancy between the clinical-radiological and the histological assessment.

BRAF (V600E) associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma.

The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF (V600E) mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF (V600E) mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF (V600E) (P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF (V600E) positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF (V600E) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.

Fine needle aspiration biopsy of intraparotid spindle cell lipoma: a case report.

Intraparotid spindle cell lipoma (SCL) of the salivary gland is a rare entity. Review of the literature revealed only two previous reports describing its cytological features. We report a case of a 44-year-old man who complained for a slowly growing, asymptomatic mass in the left parotid gland that since 12 months. Fine needle aspiration biopsy (FNAB) showed a loose collections of bland-appearing spindle cells in a myxoid background admixed with capillary fragments and some mature fat cells suggesting a diagnosis of SCL. A cytological diagnosis of mesenchymal myxoid spindle cell tumor with lipomatous differentiation, possibly an intraparotideal SCL was performed. Histological examination of the mass and the positive immunostaining for CD34 and negativity for S-100, CK-cocktail, and actin confirmed the diagnosis of SCL. The diagnosis of intraparotid SCL can be made by examining cytologic material containing mature fat with bland spindle cells in a myxoid background. FNAB diagnosis on SCL also allows to rule out other primary salivary gland tumors that may be clinically and instrumentally indistinguishable and thereby permits an appropriate surgical procedure to ensue.

Lymph node fine needle cytology in the diagnosis of infectious diseases and instrumental guides: ultrasound and computed tomography.

Imaging techniques, such as ultrasound imaging (US), computed tomography (CT), positron emission tomography-CT (PET-CT) or PET-magnetic resonance imaging (MRI), are highly accurate procedure in the lymph node enlargement detection, but none of them has the same sensitivity in the biological definition and in the cause of enlargement identification. Therefore, a direct evaluation of corresponding lymph nodes is necessary in much of the cases and Fine Needle Cytology (FNC) is one of the most frequently used technique for this purpose. The same imaging procedures are often used to perform targeted biopsies including FNC. This study discusses procedures, indications, advantages and limitations of imaging techniques as a support to FNC.

Lymph node Fine Needle Cytology, Epstein Barr virus infection and Hodgkin Lymphoma.

Epstein-Barr virus (EBV) is a double-stranded DNA virus of the herpes family; it is one of the most common human viruses and it is associated with a wide spectrum of benign and malignant conditions. EBV is related to the development of several neoplasms, globally 1% of tumours, including lymphoproliferative, epithelial and mesenchymal neoplasm. Lymphoproliferative disorders include Hodgkin lymphoma (HL) and B and T cell non-Hodgkin lymphomas. HL is one of the most common lymphoma in the developed world, affecting both young people and adults. HL pathogenesis is complex and includes various and partially unknown mechanisms. EBV has been detected in some HL neoplastic cells and expresses genes with a potential oncogenic function, therefore many studies suggest that viral infections have a causative role in neoplastic transformation. Fine Needle Cytology (FNC) is extensively used in the first diagnosis of any lymph-nodal enlargement, including reactive lymphadenopathies and lymphoproliferative processes; therefore cytopathologists are likely to encounter EBV-associated malignancies in cytology samples, mainly HL, which is one of the most common lymphoma. This study focuses on the cytological features and ancillary studies required to diagnose EBV-related HL.