Renal Angiomyolipoma: A Diagnostic and Therapeutic Challenge.

BACKGROUND: Angiomyolipomas (AML) represent less than 10% of renal tumours. They are most often detected incidentally during imaging tests, but there are several histological variants that pose difficulties in the radiological differential diagnosis. Their identification should allow the loss of renal parenchyma due to embolization or radical surgery to be prevented. METHODS: Retrospective study of patients undergoing kidney surgery with post-surgical pathological diagnosis of AML at the Álvaro Cunqueiro Hospital (2016-2021). Patients with a radiological diagnosis of AML who underwent surgery based on clinical criteria were excluded. RESULTS: 18 patients were registered, allowing for the assessment of 18 renal tumours. All of the cases were diagnosed incidentally. Preoperative radiological diagnosis was: 9 lesions suggestive of renal cell carcinoma (RCC) (50%), 7 cases suggestive of RCC vs. AML (38.9%) and 2 lesions suggestive of AML vs. retroperitoneal liposarcoma (11.1%). Histological variants of AML were found in 61.1% of cases (n = 11). The most widely used surgical technique was partial nephrectomy, in 66.67% of cases. CONCLUSIONS: The radiological differential diagnosis of AML, and particularly its variants, with malignant lesions have important limitations either due to the predominance or scarcity of any of the AML components. Some cases can also pose difficulties at the histological level. This fact highlights the importance of the specialization of uroradiologists and uropathologists and the performance of kidney-sparing therapeutic techniques.

SATB2 as a Marker of the Proximal Nephron: Expression in Nephrogenic Adenoma and Correlation With Other Renal Tubular Markers.

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.

Low-grade oncocytic tumour of the kidney is characterised by genetic alterations of TSC1, TSC2, MTOR or PIK3CA and consistent GATA3 positivity.

Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.

Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.

OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma. MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens. RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period. CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.

Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma.

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens. Multiple microscopic clear cell clusters were present in the cortex, often in subcapsular location. They were composed of large epithelial cells with strikingly clear cytoplasm, without nuclear atypia, arranged in solid nests, and some tubules with narrow lumina. Immunohistochemically, they were positive for AE1AE3, PAX 8, EMA, kidney-specific cadherin, cytokeratin 7, E cadherin, and CD117, with focal immunoreactivity for CD10. Carbonic anhydrase IX, vimentin, and markers related to apoptosis and proliferation were negative. Ultrastructurally, the cytoplasms were enlarged and poor in organelles, showing ballooning degeneration. Array comparative genomic hybridization showed no chromosomal gains or losses. Clear cell clusters constitute a rare finding in the kidney and must be differentiated from benign lesions (ectopic adrenal tissue, osmotic tubulopathy, histiocytic clusters, renal adenomas) and renal cell carcinomas. Clear cell clusters appear to be generated from "endocrine-type" atrophic tubules whose cells are enlarged due to intracellular oedema. Immunohistochemistry shows a distal nephron phenotype with a limited expression of a proximal marker, CD10. Coexisting chronic renal disease or ischemic conditions seem to be related to the development of clear cell clusters. Pathological, ultrastructural, and cytogenomic features do not support a preneoplastic nature of this lesion, at least in the cases studied here.

[E-Cadherine and GATA-3 are useful in the confirmation of the vas deferens in vasectomy specimens]. / Cadherina E y GATA-3 son útiles para confirmar la presencia de conducto deferente en muestras de vasectomía.

INTRODUCTION AND OBJECTIVES: Urologists often submit the resected tissue from vasectomies for histopathological examination in order to confirm the presence of the vas deferens. Microscopy is simple and based on haematoxylin-eosin staining; however, sample artefacts can sometimes cause confusion and immunohistochemistry can be used to identify the vas deferens. MATERIALS AND METHODS: We investigated the utility of immunohistochemical analysis using E-cadherin and GATA-3 to confirm the presence of vas deferens epithelium in 110 vasectomy sections with different artefacts, using monoclonal antibodies and a multimer conjugated with peroxidase based technique; 5 renal arteries and 5 renal veins were stained as negative controls. RESULTS: Membrane staining was observed for E-cadherin, which was moderate (2.7%) or strong (97.3%) in the vas deferens epithelium in all cases: 35 without artefacts, 7 with denuded epithelium, 56 with compressed/distorted epithelium, 8 with detached epithelium and 4 with displaced epithelium. GATA-3 showed moderate (31%) or strong (69%) nuclear staining in all cases, including the 76 with artefacts. In the control group, arteries and veins were negative for both markers in the endothelium, but GATA-3 occasionally stained lymphocytes in the blood vessel wall. CONCLUSIONS: E-cadherin membrane positivity and GATA-3 nuclear expression are useful for the identification of the vas deferens in vasectomy samples containing artefacts. Vascular endothelium is negative for both markers and any possible GATA-3 staining of the lymphocytes in the blood vessel wall should not be misinterpreted.

[New immunohistochemistry markers to determine presence of vas deferens in vasectomy specimen.] / Nuevos marcadores de inmunohistoquímica para confirmar la presencia de conducto deferente en muestras de vasectomía.

OBJECTIVES: The pathological examination of vasectomy specimens to confirm the presence of vas deferens is usually simple and is done by routine hematoxylinand eosin staining. Use of immunohistochemical techniques can aid to the diagnosis in those cases with artifacts of the epithelium, and they are also useful to differentiate vas deferens from blood vessel. We have investigated the usefulness of CD31, CD34, ERG and PAX8 for these purposes. MATERIAL AND METHODS: 81 sections from vasectomy specimens in which any section showed some kind of epithelial artifact were analyzed. Immunohistochemistry was performed with monoclonal antibodies for CD31 (clone JC70), CD34 (clone QBEnd/10), ERG (clone EPR3864) and PAX8 (clone MRQ-50). Evaluation of the vas deferens and vascular endothelial staining was done. RESULTS: Histologically, vas deferens epithelium was well-preserved in 18 sections (22.2%), denuded in 6 (7.4%), crushed or distorted in 48 sections (59.3%), detached in 5 (6,2%), and misplaced out of the vas deferens lumen in 4 (4.9%). In most of the sections the epithelium showed weak (86.4%) or moderate (9.9%) CD31 cytoplasmic staining, as well as strong nuclear PAX8 reactivity in all of the sections, exhibiting a granular pattern in the detached or artifacted epithelium. CD34 and ERG were negative in the epithelium. Capillary vessel endothelium in the vas deferens wall showed strong cytoplasmic positivity for CD31 and CD34, as well as nuclear ERG reactivity, being PAX8 negative. CONCLUSIONS: PAX8 is a useful antibody to confirm the presence of vas deferens in artifacted vasectomy specimens. CD34 and ERG are negative in the epithelium,and, otherwise, they are expressed by vascular endothelium, with the advantage of nuclear staining pattern for ERG. CD31, a classic endothelial marker, is not so specific as it had been stated as it shows weak or moderate expression in the vas deferens epithelium.

OBJETIVOS: El estudio anatomopatológico de las muestras de vasectomía para confirmar la presencia de conducto deferente generalmente es sencillo se realiza con tinción rutinaria de hematoxilina-eosina. En aquellos casos con artefacto del epitelio, el uso de técnicas de inmunohistoquímica puede ayudar al diagnóstico y sirve, además para diferenciar deferente de vaso sanguíneo. Hemos investigado la utilidad de CD31, CD34, ERG y PAX8 para estos fines.MATERIAL Y MÉTODOS: Se han estudiado 81 secciones de muestras de vasectomía en las que alguna sección presentaba algún tipo de artefacto en el epitelio. Se realizó inmunohistoquímica con anticuerpos monoclonales para CD31 (clon JC70), CD34 (clon QBEnd/10), ERG (clon EPR3864) y PAX8 (clon MRQ-50) evaluando la tinción en el epitelio deferencial y en el endotelio vascular. RESULTADOS: Histológicamente, el epitelio del conducto deferente aparecía conservado en 18 secciones (22,2%), denudado en 6 (7,4%), con artefacto de compresión o distorsión en 48 secciones (59,3%), desprendidoen 5 (6,2%) y desplazado fuera de la luz del conducto en 4 (4,9%). En la mayoría de las secciones el epitelio del CD presentó positividad citoplasmática para CD31, que fue débil (86,4%) o moderada (9,9%),y expresó intensamente PAX8 en los núcleos, con tinción granular en el epitelio denudado o artefactado. Fueron negativos CD34 y ERG. El endotelio capilar de los vasos de la pared del conducto deferente mostró intensa positividad citoplasmática para CD31 y CD34, y nuclear para ERG, siendo PAX8 negativo. CONCLUSIONES: PAX8 es un anticuerpo útil para confirmar la presencia de conducto deferente en muestras de vasectomía con artefacto. Son negativos CD34 yERG, que, por el contrario, marcan endotelio vascular, presentando ERG la ventaja de que la tinción es nuclear.CD31, marcador endotelial clásico, no es tan específicocomo se había propuesto puesto que presenta expresión débil en el epitelio del deferente.

Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity?

AIM: To describe a group of distinct low-grade oncocytic renal tumours that demonstrate CD117 negative/cytokeratin (CK) 7-positive immunoprofile. METHODS AND RESULTS: We identified 28 such tumours from four large renal tumour archives. We performed immunohistochemistry for: CK7, CD117, PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, MOC31, CK5/6, p63, HMB45, melan A, CD15 and FH. In 14 cases we performed array CGH, with a successful result in nine cases. Median patient age was 66 years (range 49-78 years) with a male-to-female ratio of 1:1.8. Median tumour size was 3 cm (range 1.1-13.5 cm). All were single tumours, solid and tan-brown, without a syndromic association. On microscopy, all cases showed solid and compact nested growth. There were frequent areas of oedematous stroma with loosely arranged cells. The tumour cells had oncocytic cytoplasm with uniformly round to oval nuclei, but without significant irregularities, and showed only focal perinuclear halos. Negative CD117 and positive CK7 reactivity were present in all cases (in two cases there was focal and very weak CD117 reactivity). Uniform reactivity was found for PAX8, AE1/AE3, e-cadherin, BerEP4 and MOC31. Negative stains included CA9, CK20, vimentin, CK5/6, p63, HMB45, Melan A and CD15. CD10 and AMACR were either negative or focally positive; FH was retained. On array CGH, there were frequent deletions at 19p13.3 (seven of nine), 1p36.33 (five of nine) and 19q13.11 (four of nine); disomic status was found in two of nine cases. On follow-up (mean 31.8 months, range 1-118), all patients were alive with no disease progression. CONCLUSION: Low-grade oncocytic tumours that are CD117-negative/CK7-positive demonstrate consistent and readily recognisable morphology, immunoprofile and indolent behaviour.

Risk of malignancy in thyroid nodules with atipia of undetermined significance.

INTRODUCTION: Prevalence of malignancy among cytologies with atypia of undetermined significance (Bethesda category III) is variable, ranging from 5%-37% in the different studies. There is thus no agreement on whether FNA should be repeated or surgery should be performed in these cases. The aim of this paper was to analyze the risk of malignancy in order to establish the most adequate clinical approach. MATERIAL AND METHODS: We analyzed 431 thyroid cytologies performed at our hospital since the introduction of Bethesda System (from January 2011 to September 2014), of which 32 (7.1%) were labeled as category III. The second FNA, when performed, and the histological results after surgery were reviewed. RESULTS: Twenty-three patients (82.1%) underwent thyroidectomy, while repeat FNA was performed in the remaining 5 patients (17.9%). Cytology was reported as benign (category II) in 3 (60%) and as unsatisfactory (category I) in 2 (40%), who underwent thyroidectomy. Thirteen of the 25 (52%) surgical thyroid specimens showed no malignancy, while differentiated thyroid carcinomas were found in 12 (48%): papillary cancer in 10 (83.3%), follicular cancer in 1 (8.3%), and papillary cancer with follicular areas in 1 (8.3%). The risk of malignancy of Bethesda category III in our patients was 42.9%-48.0%. CONCLUSION: We recommend thyroidectomy for all patients with of cytological Bethesda category III.

Needle washing increases the diagnostic yield of fine needle aspiration biopsy of the thyroid gland.

BACKGROUND AND OBJECTIVE: Nodular thyroid disease is a common condition in our clinical practice, and fine needle aspiration biopsy (FNAB) is the diagnostic procedure of choice. Its main limitation is the number of non-diagnostic samples. Since the Bethesda criteria were implemented in 2007 (a consensus document on the morphologic criteria and diagnostic terminology for interpretation of thyroid cytological samples), a higher prevalence of non-diagnostic FNAB was shown. In addition to the standard technique, we decided to collect and centrifuge the material remaining in puncture needles by washing them in a ThinPrep(®) solution, and to assess the increase in the diagnostic yield of FNAB after this change. PATIENTS AND METHODS: Systematic sampling of 168 patients who underwent FNAB at the Nutrition and Endocrinology Department of the Xeral-Cies Hospital (Vigo, Spain) from January 2010 to November 2011. Patients were classified into 2 groups: 75 patients in whom the residual material in the needle was not collected (non-washing group) and 93 patients in whom the material was collected (washing-group). All FNABs were performed by the same endocrinologist. Data are shown as percentage (± standard error) for ordinal variables or as mean (± standard deviation) for quantitative variables. A Chi-square test was used for statistical analysis of comparisons between percentages, and a Student's t test for comparisons between quantitative variables. A value of p<0.05 was considered statistically significant. RESULTS: No significant differences were found between the groups in age, sex, plasma TSH levels or nodule size. The rate of non-diagnostic FNABs was 44% (± 0.06) in the non-washing group and 17.2% (± 0.04%) in the washing group, with a significant difference (p < 0.01). DISCUSSION: Collection and subsequent processing of the residual material in the needle after FNAB significantly decreased the prevalence of non-diagnostic punctures in our patients. Collection of the residual material in the needle in this way is strongly recommended.

Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in childhood rhabdomyosarcoma.

The prognostic value of DNA ploidy and proliferative index (PI) are well established in many cancers, but their significance in childhood rhabdomyosarcoma (RMS) is unclear. We studied the DNA content and PI of 45 cases of childhood RMS obtained retrospectively. DNA histograms were hyperdiploid in 30 cases (67%), diploid in 6 (13%), tetraploid in 5 (11%), polyploid in 3 (7%), and nonclassifiable in 1 (2%). The 5-year overall survival rate by ploidy was 60% (3/5) in tetraploid, 57% (17/30) in hyperdiploid, and 0% in diploid and polyploid cases (P = .000002). The 5-year overall survival by a PI less than or greater than 19% was 62% (13/21) and 21% (5/24), respectively (P = .006). In multivariate analysis, DNA ploidy (P = .001) was an important independent prognostic factor. DNA content in childhood RMS is an important variable in predicting prognosis. DNA hyperdiploid and tetraploid rhabdomyosarcomas had a favorable prognosis, while DNA diploid and polyploid tumors had a poor prognosis.

DNA content and proliferative activity in pediatric genitourinary rhabdomyosarcoma.

Most of the studies have reported that cases of pediatric rhabdomyosarcoma (RMS) with hyperdiploid DNA and low cellular proliferative activity have better outcomes. The aim of our study was to evaluate the possible clinical relevance of DNA ploidy and proliferative activity in childhood genitourinary RMS. Twelve childhood genitourinary RMS cases were reexamined histologically and correlated with clinical features and patient survival. DNA analysis was performed on cytospin single-cell preparations obtained from the paraffin-embedded tissue blocks. MIB-1 was the proliferative marker used on paraffin sections. All patients were male with a mean age at diagnosis of 65 months. There were 5 tumors on the bladder, 5 on the pàratesticular region, and 2 on the prostate. All cases were treated with multimodality therapy using the protocols proposed by the International Society of Pediatric Oncology. The following subtypes of RMS were recognized: embryonal (n=6), spindle cell (n=4), and botryoid (n=2). DNA hyperdiploid was detected in 11 tumors (92%) and high MIB-1 index (>19%) in 4 cases (33%). Now, 10 patients are alive without evidence of disease and 2 patients are alive with evidence of disease. Our data suggested that childhood RMS of the genitourinary tract are preponderantly DNA hyperdiploid and have low cellular proliferative activity. It is also interesting that 83% of our genitourinary pediatric RMS patients are alive. As consequence of this study, we propose that DNA content and proliferative activity is a useful method to supplement findings in children with RMS.

Human Meissner corpuscles express Bcl-2 but not Bax protein.

Bcl-2 and Bax proteins play major roles in the control of apoptosis. The Bcl-2/Bax ratio is considered a marker of a cell's susceptibility to apoptotic stimuli. Immunohistochemical expression of Bcl-2 and Bax in Meissner corpuscles was investigated in 30 human skin samples. All of the Meissner corpuscles showed immunoreactivity for Bcl-2 and Bax was negative. These data support a role for Bcl-2 as a resistance mechanism of these mechanoreceptors to apoptosis.