Standardization and the histopathology of tumours

Standardization of tumor classifications is a prerequisite in facilitating international communication in cancer research. Standardized classifications are not meant to replace, or compete with, conceptual classifications. The World Health Organization's efforts in this field give consideration to definitions of tumour types, terminology, formats of categorization, and codes.     

Pathological fracture of the patella as the first presentation of renal cell carcinoma

The patella is a rare site for a metastasis to occur. We present a patient whose presenting symptom of renal cell carcinoma was a pathological fracture of the patella.     

Renal tumours of childhood: an update

The role of the pathologist has been fundamental in the progress of the treatment of paediatric renal tumours. There are different philosophies in the treatment of these tumours, and there have been many recent advances in the areas of chemotherapy, identification of new entities, prognostic histological criteria following treatment and molecular prognostic and diagnostic features. This review discusses the different approaches of the different treatment protocols from Europe and North America, and reviews staging criteria, prognostic criteria and also the different tumour entities.     

The role of cytogenetics in the classification of soft tissue tumours

 Soft tissue tumours represent a heterogeneous group of mesenchymal lesions, and their classification is the subject of continuous debate. Chromosome analysis, molecular cytogenetics and molecular assays may become increasingly useful in diagnosis, and this review summarises advances in the cytogenetic characterisation and classification of soft tissue tumours. Among the group of fibrous lesions, superficial fibromatosis exhibits trisomy 8. This genomic change is also observed in desmoid fibromatosis in association with trisomy 20. Trisomy 11 is the most frequently observed chromosomal aberration in congenital fibrosarcoma. Dermatofibrosarcoma protuberans and giant cell fibroblastoma share a translocation t(17;22), which supports the concept of the existence of a common differentiation pathway. Adipose tissue tumours is the group in which integration of genetics and pathology has been most fruitful. Ordinary lipomas cytogenetically show an abnormal karyotype in about half the cases. Genomic changes of the 11q13 region are observed in hibernoma. Lipoblastoma exhibits a specific 8q rearrangement in 8q11-q13. Loss of material from the region 16q13-qter and 13q deletions are observed in spindle cell/pleomorphic lipomas. The well-differentiated liposarcoma/atypical lipoma group is characterised karyotypically by the presence of one extra ring and/or extra giant chromosome marker. Myxoid and round cell liposarcoma share the same characteristic chromosome change: t(12;16)(q13;p11) in most cases. In the group of smooth muscle lesions most data are derived from uterine leiomyomas, which can be subclassified cytogenetically into seven different types. Half of all leiomyomas are chromosomally normal; the other half have one of six possible consistent chromosome changes. Alveolar rhabdomyosarcoma is characterised cytogenetically by two variant translocations t(2;13)(q35;q14) and t(1;13)(p36;q14). Among tenosynovial tumours, the localised type of giant cell tumour of tendon sheath exhibits two different karyotypic changes. One involves 1p11 in a translocation with chromosome 2 or with another chromosome. A second type involves 16q24. Synovial sarcoma is characterised cytogenetically by a translocation occurring between chromosome 18 and presumably two adjacent loci on the X chromosome. In neural tumours, abnormalities of chromosome 22 have been reported in benign schwannomas and perineuriomas. Malignant peripheral nerve sheath tumours exist in two main forms: sporadic and associated with the NF-1 syndrome. Karyotypes are very complex, but chromosomes 17q and 22q are very often involved. Clear cell sarcoma is characterised cytogenetically and molecularly by a translocation t(12;22)(q13;q12). The Ewing’s sarcoma/peripheral neuroectodermal tumour category shows a central karyotypic anomaly represented by the translocation t(11;22). The two variants t(21;22) and t(7;22) are found in some cases. Among cartilaginous lesion, the most frequently described anomaly is the t(9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma. Intra-abdominal desmoplastic small round cell tumour is characterised by a t(11;22)(p13;q12). Received: 5 February 1997 / Accepted: 24 February 1997     

Metastatic tumours in the testis

In a prospective autopsy study of male subjects with solic malignant neoplasms, six were shown to have metastatic deposits within the testis (2.5%). These were metastases from carcinoma of the prostate (two cases), melanoma (two cases), bronchial carcinoma (one case) and pleural mesothelioma (one case). In addition, four of 29 leukaemic patients and six of 28 with non-Hodgkin's lymphoma showed testicular involvement. The metastases from the solid tumours presented in solitary nodules, as multiple nodules or as a diffuse involvement. Microscopically, these were represented by tumour cells within the interstitial tissue without involvement of the seminiferous tubules; interstitial tissue and tubular involvement, and tumour confined to the seminiferous tubules respectively.     

Non-specific histopathological changes in kidney with renal tubular dysgenesis

Absence of proximal convoluted tubules (APCT) is a specific pathomorphological change found in kidney with renal tubular dysgenesis (RTD). Non-specific structural abnormalities in the kidney with this disorder have rarely been reported. The aim of this study was to detect non-specific histopathological changes (NSHC) in RTD kidney, to evaluate their incidence, and to establish a possible relationship to various etiological-pathogenic variants of RTD.     

Primary thymic epithelial tumours of the pleura mimicking malignant mesothelioma

AIMS: To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours. METHODS AND RESULTS: Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present. CONCLUSION: Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.     

Molecular differential pathology of renal cell tumours

Recent application of molecular cytogenetic techniques to the evaluation of renal cell tumours revealed four subtypes, each with a characteristic combination of genetic alterations within the chromosomal and mitochondrial DNA. The most common, nonpapillary renal cell carcinomas are characterized by the loss of chromosome 3p sequences, rearrangement of the chromosome 5q region and loss of the chromosome 14q sequences. Papillary renal cell tumours can be divided into two groups. Tumours with a combined trisomy of chromosomes 7 and 17 as well as loss of the Y chromosome are papillary renal cell adenomas. Tumours with additional trisomies such as trisomy 16, 20 or 12 are pipillary renal cell carcinomas. Chromophobe renal cell carcinomas show a combination of allelic losses, which do not occur in other types of renal tumours. In addition, they have a rearrangement in the mitochondrial DNA. Renal oncocytomas are benign tumours marked by normal or abnormal karyotypes with balanced or unbalanced translocations and an altered restriction pattern of the mitochondrial DNA. Although the major cytological characteristics of renal cell tumours, such as clear, granular, chromophobe and oncocytic cell phenotypes correspond to nonpapillary, papillary and chromophobe renal cell carcinomas and renal oncocytomas, there are many cases with overlapping phenotype. Therefore, a classification of renal cell tumours based on specific genetic alterations is proposed.     

Ultrastructure of streptozotocin — induced renal tumours in mice

Streptozotocin-induced tumours in the kidneys of experimental animals have been shown to be histologically similar to human renal cell carcinoma. We report the ultrastructural features of renal tumours induced in 15 mice by a single intravenous bolus of 2.5% Streptozotocin administered in a dose of 250 mg streptozotocin/kg mouse body weight. Animals were sacrificed 232–361 days after the administration of streptozotocin. On examination both kidneys from each animal contained 1–4 dysplastic tubules and 1–3 discrete tumours per kidney. Twelve dysplastic proximal convoluted tubules showing varying degrees of epithelial atypia and nine tumours exhibiting either a papillary or solid architecture were examined. Dysplastic epithelial cells and tumours of papillary and solid type exhibited complex cell borders with well-developed junctional complexes. The majority of cells contained surface microvilli, and in some cells microvilli-lined intracytoplasmic lumina were observed. Occasional dysplastic epithelial cells and tumour cells contained double-membrane vesicles 120–200 nm in diameter. These were similar to the intracytoplasmic vesicles characteristic of human chromophobe renal cell carcinoma. Intracytoplasmic collections of glycogen granules and flocculant protein were identified in both dysplastic and neoplastic cells, and where prominent they resulted in compression of cytoplasmic organelles. Coated vesicles were commonly observed. These were free within the cytoplasm and were also seen budding from strands of rough endoplasmic reticulum. The distribution of these vesicles suggested a role in protein transport from the rough endoplasmic reticulum. It is concluded that while streptozotocin-induced renal tumours have some ultrastructural features in common with human chromophobe renal cell carcinoma, the overall ultrastructural morphology differs significantly from that described for the various histological types of human renal cell carcinoma.     

Epithelial tumours of the adult kidney

 The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation. Received: 3 December 1998 / Accepted: 3 December 1998     

Sex cord-stromal tumours of the ovary

The aim of this review is to give a reasonably concise resumé of our knowledge of the sex cord-stromal tumours of the ovary. Lipoid cell tumours of the ovary are often included within this broad category but this poorly defined and heterogenous group of neoplasms will not be considered here. This review is a selective one and no attempt is made to cover all aspects of sex cord-stromal tumours or to provide a complete bibliography. The histological features of many of the neoplasms in this group, particularly those which have been recently defined, are discussed but a consideration of differential histological diagnosis is excluded. The ultrastructural characteristics of the various neoplasms are considered only in terms of their relevance to histogenesis or metabolic activity.     

Klassifikation der Nierenzellkarzinome/Tumoren und ihre Beziehung zum Nephron-Sammelrohrsystem

Summary After a controversial phase of nomenclature (including — among others — the terms hypernephroma and hypernephroid carcinoma) a cytomorphologically defined subtyping of renal cell tumours (adenomas, carcinomas, oncocytomas) is offered, based on new electron microscopical and histochemical observations. These data are in part supported by cytogenetical findings reported in the literature. Phenotypical/histogenetical relations to different parts or cell types, respectively, of the nephron-collecting duct system could be demonstrated. Chromophobe cell carcinoma and oncocytoma exhibit features of the intercalated cells.

Herrn Prof. Dr. Dr. h.c. Adalbert Bohle gewidmet     

The expression of 3-fucosylated-N-acetyl lactosamine carbohydrate determinants in renal tumours

The distribution in renal tumours of 3-fucosyl-N-acetyl lactosamine has been studied by using the monoclonal antibodies AGF 4.36 and AGF 4.48 and immunoperoxidase methods on tissue sections. Seven of 19 nephroblastomas and 12 of 30 renal cell carcinomas contained the epitope. In nephroblastomas the epitope was found on the terminals of type B tubules in six cases and in one case on the type A or neoplastic tubules. In renal carcinoma the antigen was found on the surface of tumour cells. The results suggest that in kidneys bearing nephroblastomas ureteric bud elements may grow into the tumour from the adjacent kidney.     

Renal cysts and associated renal tumours in male ddY mice injected with ferric nitrilotriacetate

In experiments using ferric nitrilotriacetate (Fe-NTA) as a renal carcinogen, multiple renal cysts are often observed in addition to renal tumours. In the present study, we used 3-week-old male ddY mice and examined the relation between renal cysts and cancer development. Four months after the start of Fe-NTA administration, we observed cysts in the renal cortex in all Fe-NTA-treated mice, but not in Fe-free NTA-treated mice. Three types of cysts were observed, but only those which originated from the renal proximal tubules showed multi-layered or papillary growth of cyst epithelial cells. Using histochemical staining, we found a cyst formation-tumour induction sequence, and the supposed cystic-papillary tumour induced by Fe-NTA was of proximal tubular cell origin. We also found that the minimum dose of Fe-NTA capable of inducing renal tumours in ddY mice was 10 mg of iron/kg/day, four times in 2 weeks.     

Primary lymphomas of the gastrointestinal tract I. Plasma cell tumours

The histology of 125 cases of primary gastrointestinal lymphomas arising in the stomach and small and large intestine has been reviewed. The material was gathered from the Bland-Sutton Institute of Pathology at the Middlesex Hospital and from the Westminster Hospital. Of the initial total of 143 cases diagnosed, 18 were rejected. Of the acceptable 125 cases, 51 lymphomas were arising in stomach, 53 in the small intestine and 21 in the large intestine including rectum. Excluding the four children in the series, ages ranged from 18 to 82 and were fairly evenly distributed across the decades. There was no significant sex difference in the Middlesex Hospital cases but in the Westminster Hospital series the male to female ratio was approximately 2.6 to 1. One significant finding to emerge from this histological survey, and which forms the basis of this communication, is the proportion of lymphomas considered to be predominantly of plasma cell type. These plasma cell tumours, or extramedullary plasmacytomas, accounted for 49 out of the 125 cases (39%) of gastrointestinal lymphomas. They were less common in stomach and most common in the intestine, the majority occurring in the ileocaecal region. Conversely, Hodgkin's disease, in contrast to some series, was not encountered. Of the non-Hodgkin's lymphomas, grade I tumours were uncommon and true histiocytic lymphomas were distinctly rare. The high incidence of plasma cell tumours were uncommon and true histiocytic lymphomas were distinctly rare. The high incidence of plasma cell tumours in our series is in keeping with the morphological findings of a previous study carried out in patients with alpha-chain disease and in a small series of primary gastrointestinal lymphomas.     

Adenomatoid tumours of the uterus

In order to assess the incidence of adenomatoid tumours in the uterus, 1000 hysterectomy specimens were cut into 1 mm slices and all myometrial lesions examined microscopically. Twelve of the uteri (1.2%) contained 14 adenomatoid tumours. In 308 specimens in which both Fallopian tubes were present only one adenomatoid tumour was found in the tube indicating the relative frequency of occurrence of this lesion in the uterus and the Fallopian tube. Where recorded, 10 of the 14 uterine tumours were in the fundus. Seven were subserosal and seven were intra-mural. Microscopically, they presented with plexiform, tubular, canalicular or mixed growth patterns. There was no relationship between the presence of these tumours and other uterine pathology and they are regarded as incidental findings.     

The World Health Organization 2016 classification of testicular non‐germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel

The World Health Organization (WHO) released a new tumour classification for the genitourinary system in early 2016 after consensus by pathologists with expertise in these organs. It utilized the framework of the 2004 classification, and incorporated the most up‐to‐date information concerning these tumours. In testicular tumours, the majority of the changes occurred in the nomenclature and classification of germ cell tumours; however, several modifications were also made for non‐germ cell tumours. Among sex cord–stromal tumours, sclerosing Sertoli cell tumour (SCT) is no longer recognized as a separate entity but as a morphological variant of SCT not otherwise specified (NOS), as CTNNB1 gene mutations have been noted in both neoplasms but not in the other forms of SCT. Similarly, the lipid cell variant is not separately classified, but is considered to be a morphological variant of SCT NOS. Large‐cell calcifying SCT is recognized as a distinct entity that occurs either sporadically or in association with Carney complex, with the latter patients having a distinct germline PRKAR1A gene mutation. Intratubular large‐cell hyalinizing Sertoli cell neoplasia is also accepted as a separate entity linked with Peutz–Jeghers syndrome. The subcategories of ‘mixed’ and ‘incompletely differentiated’ forms of sex cord/gonadal stromal tumours have been replaced by ‘mixed and unclassified sex cord–stromal tumours’. New entities introduced in the latest WHO revision include: myoid gonadal stromal tumour and ‘undifferentiated gonadal tissue’, a putative precursor lesion of gonadoblastoma, whereas juvenile xanthogranuloma and haemangioma are included in the miscellaneous category of tumours.     

Over-expression of glucose transporter isoform GLUT1 and hexokinase I in rat renal oncocytic tubules and oncocytomas

Renal oncocytomas, which have previously been shown to originate from the collecting duct system, were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. Oncocytic tubules connected with collecting ducts were first observed 23 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical pattern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly increased; activities of HK, PK and MDH were elevated, while LDH activity was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumours, such as clear/acidophilic and basophilic cell tumours. The characteristic over-expression of GLUT1 may be used as a diagnostic criterion for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced expression of this glucose transporter protein.