Clear cell papillary neoplasm of the breast with MAML2 gene rearrangement: Clear cell hidradenoma or low-grade mucoepidermoid carcinoma?

Clear cell hidradenoma (CCH) is an uncommon adnexal tumor usually arising from eccrine glands and commonly seen on the face and the upper extremities. CCH occurring in the breast is extremely rare. Herein we report a case of MAML2-rearranged CCH of breast with a papillary architecture closely mimicking intraductal papilloma, adenomyoepithelioma and low-grade mucoepidermoid carcinoma, thus representing a source of diagnostic confusion. An overview of salient histologic features and immunophenotypes to distinguish CCH and low-grade mucoepidermoid carcinoma is also integrated into the report.     

Sinonasal haemangiopericytoma‐like tumour: a sinonasal glomus tumour or a haemangiopericytoma?

AIMS: Sinonasal haemangiopericytoma-like tumour is controversial with regard to its nosologic nature. This study aims to investigate its relationship with glomus tumour and haemangiopericytoma. METHODS AND RESULTS: Six cases of sinonasal haemangiopericytoma-like tumours identified in our files were reviewed for clinicopathological features, and compared with five cases each of soft tissue glomus tumour and meningeal haemangiopericytoma. Immunohistochemical studies for muscle-specific actin, smooth muscle actin, desmin and CD34 were performed. Sinonasal haemangiopericytoma-like tumour demonstrated a uniform histological appearance with bland-looking short, spindly cells forming sheets and short fascicles. The tumour cells were interspersed with slit-like, round and ectatic blood vessels. Actin immunoreactivity was demonstrated in all six cases, although occasionally patchy. The histological appearance and immunohistochemical phenotype of sinonasal haemangiopericytoma-like tumour were very similar to and focally indistinguishable from glomus tumour. Meningeal haemangiopericytoma, in contrast, was characterized by high tumour cellularity, random nuclear orientation, presence of staghorn vasculature and lack of immunohistochemical evidence of myogenic differentiation. CONCLUSIONS: We conclude that sinonasal haemangiopericytoma-like tumour is biologically close to or identical to glomus tumour, but is not related to haemangiopericytoma.     

Are molecular features of a chromophobic cell renal cell carcinoma correlated with clinical findings?

Lipids extracted from three human renal neoplasms have been characterized by means of 13C magnetic resonance spectroscopy. The presence of free cholesterol, high levels of unsatured fatty acids, and phosphatidylcholine, and a very high fatty acids/cholesterol ratio makes the lipid profile of a rare chromophobe cell carcinoma very similar to that of an oncocytoma. On the contrary, clear cell carcinomas are mainly characterized by the presence of almost fully esterified cholesterol and by a markedly lower level of unsatured fatty acids. Since chromophobic cell carcinomas have a more favourable prognosis than clear cell carcinomas, their analogy in the lipid composition with a benign renal neoplasm could have a clinical significance. In particular, our report suggests that cholesteryl esters and high levels of unsatured fatty acids could be a marker of a poor (clear cell carcinomas) or a good (chromophobic cell carcinomas) prognosis, respectively. More in depth studies are required of the molecular composition of the neoplastic pathologies that add new knowledge, with potential clinical implications.     

Pediatric renal cell carcinomas: where do they fit in the new histologic classification of renal cell carcinoma?

Genetic, immunohistochemical, and histologic data has led to the reclassification of renal cell carcinoma in the last decade. Recent studies suggest that renal cell carcinomas in children and young adults may represent a distinct group of tumors. These tumors have unique genetic findings (most commonly t(x;1)(p11:q21)), a predominantly papillary architecture, numerous calcifications, granular cytoplasm, and a possible relationship with neuroblastoma.     

Peripheral T cell lymphomas with follicular T helper phenotype: a new basket or a distinct entity? Revising Karl Lennert’s personal archive

Agostinelli C, Hartmann S, Klapper W, Korkolopoulou P, Righi S, Marafioti T, Piccaluga P P, Patsouris E, Hansmann M‐L, Lennert K & Pileri S A
(2011) Histopathology 59 , 679–691 Peripheral T cell lymphomas with follicular T helper phenotype: a new basket or a distinct entity? Revising Karl Lennert’s personal archive Aims: To revise 25 cases selected from Karl Lennert’s personal archive (21) and Bologna and Frankfurt Registries (four) because of cytological similarities. Methods and results: All cases were provided with paraffin blocks and studied by immunohistochemistry and molecular techniques. While phenotyping was very informative, among molecular studies only EBER in situ‐hybridization (ISH) was successful. Twenty‐two cases were concluded as peripheral T cell lymphomas (PTCL). Of these, six were reclassified as angioimmunoblastic T cell lymphoma (AITL), 13 as PTCL, not otherwise specified (NOS), including four follicular variants and one tumour with T‐zone pattern, and three as borderline tumours between AITL and PTCL/NOS. All these cases consisted homogeneously of small/medium‐sized elements with mild nuclear atypia and an evident rim of clear/pale cytoplasm. On immunohistochemistry, they regularly expressed three to six follicular helper T cell (FTH)‐associated markers. EBER–ISH revealed scattered EBV‐infected B cells in all tumours except those with ‘follicular’ growth pattern. The content of follicular dendritic cells and high‐endothelial venules varied significantly depending on the histotype. Conclusions: This study shows that: (i) historical material can be still employed usefully, and (ii) the FTH‐phenotype corresponds to a broad spectrum of PTCLs that might form a new category to be validated in future molecular and clinicopathological analyses.     

Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma?

AIMS: Acinic cell-like breast carcinoma is a newly recognized entity, and few acinic cell-like breast carcinoma cases have been reported. All reported acinic cell-like breast carcinomas were counterparts of the solid type of acinic cell carcinoma of the salivary gland. We report here three cases of secretory breast carcinoma with acinic cell differentiation, and discuss the similarity between secretory breast carcinoma and acinic cell carcinoma of the salivary gland. METHODS AND RESULTS: The cases were histologically identical to acinic cell carcinoma of the salivary gland: papillary-cystic type in case 1, a mixture of papillary-cystic, microcystic and follicular type in case 2, and microfollicular type in case 3. Immunohistochemically, the tumour cells were positive for salivary-type amylase, lysozyme, S100 protein and alpha 1-antitrypsin, and negative or less reactive for gross cystic disease fluid protein-15 and oestrogen receptor. All three cases did not reveal metastasis or recurrence. CONCLUSIONS: These cases were typical of secretory breast carcinoma, and were clinically, histologically and immunohistochemically analogous to acinic cell carcinoma of the salivary gland. We emphasize that secretory breast carcinoma and acinic cell carcinoma of the salivary gland may be identical lesions.     

Pseudocapsule of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion: a clue for tumor enucleation?

Objectives: To evaluate the feasibility and efficacy of tumor enucleation (TE) for patients with small renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) by analyzing the pseudocapsule characteristics of Xp11.2 RCCs comparing with that of clear cell renal cell carcinoma (ccRCC). Methods: From June 2007 to February 2014, 22 patients with Xp11.2 RCC who were diagnosed by fluorescence in-situ hybridization polyclonal (FISH) assay and 32 patients with ccRCC treated in our institution were comparatively studied. 12 patients with ccRCC underwent radical nephrectomy (RN) and 20 received TE. Among 22 patients with Xp11.2 RCC, 19 were treated by RN and 3 by TE (1 by radiofrequency ablation assisted TE). Pseudocapsule and other clinicopathological characteristics of the two subtypes of RCC were compared. Survival of patients treated with different surgical methods was evaluated and compared. Results: Pseudocapsule incidence of Xp11.2 RCC (14/22, 63.6%) was lower than that of ccRCC (32/32, 100%, P<0.001). However, pseudocapsule integrity rate of Xp11.2 RCC (10/14, 71.4%) was comparable with that of ccRCC (23/32, 71.9%, P=1.000). The 5-year overall survival of patients with ccRCC treated with RN and TE was 86% and 81%, respectively (P=0.845). Three patients with small Xp11.2 RCC performed well after TE. Conclusions: Over half Xp11.2 RCC had pseudocapsules, whose integrity rate was comparable to that of ccRCC. Treatment effectives of TE and RN were comparable in ccRCC. A preliminary attempt to treat small Xp11.2 RCC with intact pseudocapsule by using TE produced a favorable treatment outcome.     

Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?

We describe a large inbred Syrian pedigree with an autosomal recessive neurodegenerative disorder. The clinical picture of the affected patients is oligodontia, and a degenerative neurological condition with onset around age 12, characterized by progressive ataxia and pyramidal syndrome. Abnormalities in the white matter and cortical atrophy were assessed by magnetic resonance imaging. Differential diagnosis and the possibility of a fortuitous association or the report of a hitherto unreported dento-leukoencephalopathy are discussed.     

γδ T‐cell lymphomas: a homogeneous entity?

gammadelta T-cells comprise an immunologically distinct lymphoid population, characterized by specific morphological, phenotypical and functional properties. Therefore it seems reasonable to speculate that neoplasms derived from this particular T-cell subset display distinct features. Indeed, the prototype gammadelta T-cell lymphoma, hepatosplenic T-cell lymphoma constitutes a unique clinicopathological entitity which is intimately associated with a gammadelta T-cell phenotype. However, gammadelta T-cell lymphomas have also been described in other extranodal sites where, unlike reactive gammadelta T-cells and hepatosplenic gammadelta T-cell lymphomas, they display an important morphological heterogeneity. Moreover, these nonhepatosplenic gammadelta T-cell lymphomas are essentially not that different from their alphabeta T-cell receptor for antigen (TCR)-expressing counterparts and thus may be incorporated in the established T-cell lymphoma subclasses. However, subtle differences regarding their histopathological appearance as well as their biological behaviour indicate that further studies to determine the exact significance of TCR expression are required. Such inquiries may contribute to the general understanding of T-cell lymphomagenesis in general, which is still obscure.     

The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1α and -2α in sporadic clear cell renal carcinoma

Decreased levels of von Hippel-Lindau (VHL) tumour suppressor protein are associated with up-regulation of hypoxia-inducible factor (HIF), leading to increased tumour proliferation, angiogenesis and progression. The role of erythropoietin (EPO), a target gene for HIF, remains unknown for sporadic clear cell renal cell carcinoma (sCCRCC). In this study, we determined expression levels of EPO, and its correlation with VHL mutations and HIF-1α and HIF-2α expression in 82 patients identified with sCCRCC following nephrectomy. We identified VHL gene alterations using multiplex polymerase chain reaction, purifying products of polymerase chain reaction, and direct sequencing. Immunohistochemical staining for HIF-1α, HIF-2α and EPO was performed for tumour and corresponding normal tissues. Data were analyzed with respect to clinicopathological factors. EPO was detected in 87.8% of sCCRCC tumours versus 7.3% for normal tissues. EPO expression was related to tumours demonstrating VHL gene abnormalities. Of specimens with VHL alterations 95.6% tested positive for EPO, versus 78.3% when VHL gene expression was normal (P<0.01). EPO was identified in 96.2 and 94.2% of HIF-1α and HIF-2α positive specimens, respectively, compared to 72.4 and 53.8% for HIF-1α and HIF-2α negative groups (p<0.01). Moreover, EPO expression correlated significantly with increasing nuclear grade (p<0.05). HIF-2α was identified in 84.1% of sCCRCC, compared to 64.6% for HIF-1α. Expression of HIF-1α, HIF-2α and EPO is common in sCCRCC. Although both forms of HIF up-regulate expression of EPO, the relationship to HIF-2α appears to be more pronounced. The VHL-HIF-EPO pathway requires further study, as it may represent a potential molecular target for therapy of sCCRCC.     

Fine‐needle aspiration of renal cell carcinoma: Is accurate Fuhrman grading possible on cytologic material?

The Fuhrman grading system of renal cell carcinoma (RCC) consists of four grades based on nuclear size/contour and nucleolar conspicuousness. Fuhrman grading of histpathologic material is an independent prognostic parameter for RCC. Although widely used in surgical pathology, Fuhrman grading is not routinely performed on cytologic material. Thirty-three cases of renal fine needle aspirations (FNAs) with histologically proven RCC were retrieved from the cytopathology archives at Johns Hopkins Hospital. Fuhrman grade was determined independently and blindly by three faculty cytopathologists and compared with the Fuhrman grade of the subsequent surgical pathology specimen. The 33 resection specimens had the following Fuhrman grades: 0/33, grade I; 24/33 (73%), grade II; 9/33 (27%), grade III; and 0/33, grade IV. After Fuhrman grading was applied to the FNA material, diagnostic sensitivity was 83% for grade II versus 44% for grade III. The specificity and accuracy were 50 and 75%, respectively, for grade II versus 100% and 84% for grade III. Diagnostic sensitivity for grade II tumors ranged from 38 to 83%, grade III 44-62%. Diagnostic specificity for grade II tumors ranged from 50 to 78%, grade III 80-100%. Accuracy ranged from 48 to 75% for grade II and 75-87% for grade III. Using a two-tier grading model, accuracy improved to 84.2%. In our experience, Fuhrman grading of FNA specimens yielded variable results. There was only moderate agreement between cytopathologists, with an overall tendency to undergrade the tumor when compared with the resection specimen. Averaging the participants' grading and using a two-tier instead of four-tier system improved overall performance.     

T‐cell migration: a naive paradigm?

Naive T cells have long been thought to recirculate exclusively between secondary lymphoid organs via the lymph and blood. Evidence is now emerging that this view may be too simplistic and that naive T cells routinely traffic through non-lymphoid organs in a manner similar to that of memory T cells, albeit in lower numbers. This represents a fundamental shift in the current paradigm of T-cell migration through different types of tissue. This review summarizes these recent findings, along with the similarities and differences in migratory properties of naive and memory T cells, and discusses how and why naive T cells might access non-lymphoid tissues.