Hypoplasia is defined in the Merriman-Webster dictionary as “a condition of arrested development in which an organ, or part, remains below the normal size, or in an immature state.” The degree of ...reduced size is not definitional. Renal hypoplasia, however, has historically been defined as a more marked reduction in renal mass such that presentation in childhood is the norm. There are 3 commonly recognized types of renal hypoplasia, simple hypoplasia, oligomeganephronic hypoplasia (oligomeganephronia) and segmental hypoplasia (Ask-Upmark kidney). They have in common a reduction in the number of renal lobes. A fourth type, not widely recognized, is cortical hypoplasia where nephrogenesis is normal but there is a reduction in the number of nephron generations. Recently there has been great interest in milder degrees of reduced nephron mass, known as oligonephronia because of its association with risk of adult-onset hypertension and chronic kidney disease. Since the last pathology review of this topic was published by Jay Bernstein in 1968, an update of the renal pathology findings in renal hypoplasia is provided with a review of 18 new cases. The renal hypoplasias are then framed within the modern concept of oligonephronia, its diverse causes and prognostic implications.
The past two decades have witnessed recognition of several new types of renal cell carcinoma, each with distinct cytogenetic abnormalities. Included are several genetic and acquired cystic kidney ...diseases associated with development of renal cell carcinoma, the topic of this review. The risk in patients with autosomal dominant polycystic kidney disease is not accurately known but may be slightly increased. The risk for patients with von Hippel-Lindau disease is substantial, and death from renal cancer is common. For patients with tuberous sclerosis complex, the challenge is recognition of the occasional malignancy arising in a field of many benign tumors. Patients with end-stage kidney disease and acquired cystic kidney disease may develop a variety of renal cell carcinoma types. Progress in understanding the molecular basis of renal cyst formation and neoplastic disease has fostered development of targeted therapies that now hold promise for a group of neoplasms whose cure was traditionally dependent on surgical approaches.
The kidney is one of the most complicated organs in development and is susceptible to more types of diseases than other organs. The disease spectrum includes developmental and cystic diseases, ...involvement by systemic diseases, iatrogenic complications, ascending infections and urinary tract obstruction, and neoplastic diseases. The diagnosis of kidney disease is unique involving 2 subspecialties, urologic pathology and renal pathology. Both renal and urologic pathologists employ the renal biopsy as a diagnostic modality. However, urologic pathologists commonly have a generous specimen in the form of a nephrectomy or partial nephrectomy while a renal pathologist requires ancillary modalities of immunofluorescence and electron microscopy. The 2 subspecialties differ in the disease spectrum they diagnose. This separation is not absolute as diseases of one subspecialty not infrequently appear in the diagnostic materials of the other. The presence of medical renal diseases in a nephrectomy specimen is well described and recommendations for reporting these findings have been formalized. However, urologic diseases appearing in a medical renal biopsy have received less attention. This review attempts to fill that gap by first reviewing the perirenal anatomy to illustrate why inadvertent biopsy of adjacent organs occurs and determine its incidence in renal biopsies followed by a discussion of gross anatomic features relevant to the microscopic domain of the medical renal biopsy. Unsuspected neoplasms and renal cysts and cystic kidney diseases will then be discussed as they create a diagnostic challenge for the renal pathologist who often has limited training and experience in these diseases.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. ...Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.
A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and cystic growth was recently reported in patients with tuberous sclerosis complex (TSC). We searched multiple institutional ...archives and consult files in an attempt to identify a sporadic counterpart. We identified 16 morphologically identical cases, all in women, without clinical features of TSC. The median age was 57 years (range, 31 to 75 y). Macroscopically, tumors were tan and had a solid and macrocystic (12) or only solid appearance (4). Average tumor size was 50 mm (median, 38.5 mm; range, 15 to 135 mm). Microscopically, the tumors showed solid areas admixed with variably sized macrocysts and microcysts that were lined by cells with a pronounced hobnail arrangement. The cells had voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to oval nuclei with prominent nucleoli. Scattered histiocytes and lymphocytes were invariably present. Thirteen of 16 patients were stage pT1; 2 were pT2, and 1 was pT3a. The cells demonstrated a distinct immunoprofilenuclear PAX8 expression, predominant CK20-positive/CK7-negative phenotype, patchy AMACR staining, but no CD117 reactivity. Thirteen of 14 patients with follow-up were alive and without disease progression after 2 to 138 months (mean53 mo; median37.5 mo); 1 patient died of other causes. Although similar to a subset of renal cell carcinomas (RCCs) seen in TSC, we propose that sporadic “eosinophilic, solid, and cystic RCC,” which occurs predominantly in female individuals and is characterized by distinct morphologic features, predominant CK20-positive/CK7-negative immunophenotype, and indolent behavior, represents a novel subtype of RCC.
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most frequent genetic causes for kidney failure (KF) in children and adolescents. Over 20 genes cause NPHP ...and over 90 genes contribute to renal ciliopathies often involving multiple organs. About 15–20% of NPHP patients have additional extrarenal symptoms affecting other organs than the kidneys. The involvement of additional organ systems in syndromic forms of NPHP is explained by shared expression of most
NPHP
gene products in centrosomes and primary cilia, a sensory organelle present in most mammalian cells. This finding resulted in the classification of NPHP as a ciliopathy. If extrarenal symptoms are present in addition to NPHP, these disorders are defined as NPHP-related ciliopathies (NPHP-RC) and can involve the retina (e.g., with Senior-Løken syndrome), CNS (central nervous system) (e.g., with Joubert syndrome), liver (e.g., Boichis and Arima syndromes), or bone (e.g., Mainzer-Saldino and Sensenbrenner syndromes). This review focuses on the pathological findings and the recent genetic advances in NPHP and NPHP-RC. Different mechanisms and signaling pathways are involved in NPHP ranging from planar cell polarity, sonic hedgehog signaling (Shh), DNA damage response pathway, Hippo, mTOR, and cAMP signaling. A number of therapeutic interventions appear to be promising, ranging from vasopressin receptor 2 antagonists such as tolvaptan, cyclin-dependent kinase inhibitors such as roscovitine, Hh agonists such as purmorphamine, and mTOR inhibitors such as rapamycin.
Renal cystic diseases and congenital abnormalities of the kidney and urinary tract comprise a heterogeneous group of lesions whose pathogenesis has eluded physicians for centuries. Recent advances in ...molecular and genetic understanding of these diseases may provide the solution to this riddle.
The formulation of an effective classification system for these disorders has been elusive but is needed to introduce order while providing a conceptual framework for diagnosis.
This review discusses the evolution, beginning in the 19th century, of postulates regarding the pathogenesis of cystic and developmental renal diseases. Selected classification systems proffered during this period are discussed in pursuit of an ideal classification schema that would account for morphologic features and their clinical importance, with logical links to pathogenesis and treatment. Although this remains an elusive target, its general outline is becoming clearer. A classification approach favored by the author is presented, which incorporates many of the strengths contained in several previous classifications.
Genetic-and molecular-based postulates regarding the pathogenesis of the renal cystic and developmental diseases have implicated mutated master genes and the modification of genes that are crucial in renal development and genes that are central to the sensory effects of the renal tubular primary cilium on cell physiology. These scientific advances provide pathogenetic links between morphologically and genetically distinct entities and certain cystic and neoplastic entities, associations that seemed implausible not long ago. These advances may eventually provide the basis for future classification systems while suggesting targets for therapeutic approaches in the prevention and treatment of these diseases.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy that is a leading genetic etiology of end-stage renal disease in children and young adults. Approximately 60% of patients ...with a known genetic etiology of nephronophthisis are due to homozygous deletion of the NPHP1 gene. We identified a total of 45 renal biopsies from young patients with chronic kidney disease of undetermined etiology and analyzed them for the possibility of nephronophthisis due to NPHP1 deletion using interphase fluorescence in situ hybridization and/or polymerase chain reaction. Homozygous NPHP1 deletion was identified in 9 patients (20%). In cases with adequate tissue, both assays were performed and showed 100% agreement. Blinded histopathologic analysis was then performed and identified 6 lesions that were significantly more common in biopsies from patients with NPHP1 deletion–proven nephronophthisis than chronic kidney injury of other known etiologies. Many of the classically described nephronophthisis biopsy lesions such as tubular basement membrane duplication, presence of cysts, and mononuclear interstitial inflammation were not significantly associated with this disease when compared with biopsies from patients with chronic kidney injury due to other etiologies. There were, however, morphologic lesions that were strongly associated with NPHP1 deletion including tubular abnormalities such as diverticulum, florets, and macula densa–like change as well as interstitial Tamm-Horsfall aggregates, periglomerular fibrosis, and the absence of arteriosclerosis. Awareness of the histopathologic pattern of injury in nephronophthisis combined with testing for NPHP1 deletion enables renal pathologists to provide a definitive pathologic and genetic diagnosis in a subset of patients with this disease.
•A fluorescence in situ hybridization assay for the detection of nephronophthisis due to homozygous deletion of NPHP1 was validated.•Homozygous NPHP1 deletion was detected in 9 (20%) of 45 renal biopsies from young patients with chronic kidney disease of undetermined etiology.•Six histopathologic lesions were found to be more common in biopsies from patients with NPHP1 deletion–proven nephronophthisis than chronic kidney injury of other known etiologies.
A total of 100 renal cell carcinomas were prospectively examined for renal sinus invasion, 74 clear cell renal cell carcinomas (CC), 3 renal cell carcinomas, unclassified (RUC), 16 papillary renal ...cell carcinomas (PapC), and 7 chromophobe renal cell carcinomas (ChC). Using the 2002 TNM staging formulation, 49 tumors were T1, 5 were T2, and 46 were T3 or T4. Renal sinus invasion occurred more often than renal capsule invasion. No tumor invaded the capsule that did not also invade the sinus. Renal sinus invasion correlated with Fuhrman grade; 17% of grades 1/2 tumors invaded the sinus, while 71% of grade 3/4 tumor invaded the sinus (P < 0.001). Sinus invasion correlated with tumor type; 2 of 23 PapC and ChC invaded the sinus compared with 44 of 77 CC and RUC. Sinus invasion occurred in approximately 16% of tumors 1 to 4 cm in size, then abruptly increased for larger tumors (P < 0.001). When tumors are staged by the 1997 and 2002 TNM formulation, renal sinus invasion upstaged 28% of cases stage T1 or T2 by the 1997 formulation, to T3 using the 2002 criteria. In conclusion, renal sinus invasion is the most common site of extrarenal extension of renal carcinoma and correlates with tumor type, grade and size. Appropriate evaluation for sinus invasion reduces the incidence of T1b and T2 CC tumors, limiting prognostic utility and suggesting reassessment of the T1 and T2 stage designations.
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