Benign tumors and tumor-like lesions of the adult kidney. Part I: Benign renal epithelial neoplasms

The spectrum of renal neoplasms has expanded in recent years. Although most of the work taking place in this field has concerned malignant neoplasms of the kidney, there have been significant improvements in our knowledge of benign renal tumors and tumor-like lesions, especially in renal cell adenoma, renal oncocytoma, and renal angiomyolipoma. Awareness and knowledge of these benign lesions is important because they are often included in the differential diagnoses of malignant tumors, with which they may be confused both clinically and pathologically. The authors review the topic of benign renal neoplasms and tumor-like lesions that occur in adults, emphasizing some of the newly described aspects of these lesions.     

Benign anal and perianal polypoid neoplasms and tumor-like lesions

Mesenchymal anal and perianal tumors are relatively uncommon. The majority are malignant. Benign mesenchymal anal tumors are rare. Some are common stromal neoplasms, but with the rare presentation as anal polyps. Other lesions are rare, but unique to the anal/perianal region. Common keratinous cysts might uncommonly present as anal polyps, while other rare cysts are unique to the anogenital region.     

Benign tumors and tumor-like lesions of the gallbladder and extrahepatic biliary tract

The gallbladder is one of the most common specimens encountered in surgical pathology laboratories worldwide. A vast majority of these show merely cholelithiasis and chronic cholecystitis, however, a wide variety of benign tumors and tumor-like lesions can occur in the gallbladder and are largely discovered incidentally. Benign tumors of the gallbladder and extrahepatic bile ducts are similar, however, the incidences vary by site. The epithelial tumors include adenomas that can be gastric, intestinal or biliary types, and cystadenomas. Mesenchymal tumors are even more rare and identical to their soft tissue counterparts. Of these as a group, the neurogenic lesions are most common. The tumor-like lesions include various types of metaplasia, hyperplasia, heterotopia and chronic cholecystitis-associated lesions. These various benign and tumor-like lesions can mimic malignancy clinically, radiologically and sometimes even microscopically. Awareness of these benign lesions is necessary to avoid a wrong diagnosis of malignancy.     

Soft tissue tumors of the urinary bladder Part II: malignant neoplasms

Most bladder tumors arise from the urothelium. However, there are several uncommon but significant malignant bladder lesions that must be differentiated from urothelial carcinomas and from benign lesions of the bladder. The second half of this two-part review will describe rare nonurothelial malignant tumors of the urinary bladder including leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, malignant fibrous histiocytoma (undifferentiated sarcoma), primitive neuroectodermal tumor, malignant peripheral nerve sheath tumor, hemangiopericytoma, and alveolar soft-parts sarcoma. Common clinical presentations, morphologic characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. Because the distinction between malignant and benign lesions has significant therapeutic and prognostic implications, key factors for differentiating them are presented.     

Unusual benign polypoid and papular neoplasms and tumor-like lesions of the vulva

We aimed to investigate the prevalence and spectrum of unusual benign neoplasms and tumor-like lesions presenting as vulvar polyps and papules, to study their clinical, pathologic, hormonal, and developmental features and whether they have important associations with other pathologic lesions or clinical diseases. We conducted a retrospective review study of 115 vulvar specimens over 7 years. Common lesions, for example, fibroepithelial polyps, skin tags, papillomas, abscesses, viral warts and common cysts, were excluded. We found 21 cases (18%) with uncommon benign vulvar lesions. They included 7 epithelial cysts, 3 vascular lesions, 3 glandular neoplasms, 3 endometrioses, 1 caruncle, 1 pilonidal sinus, 1 prolapsed urethra, 1 seborrheic keratosis, and 1 granular cell tumor. The age range was between 1 and 64 years with a mean age of 33 years. Most (86%) were 2.5 cm or less. Many were asymptomatic incidental pathologic findings that can be missed clinically. Nine cases have important clinical associations or coexisting incidental pathologic lesions. Some lesions demonstrated hormone receptors. Some were clinically confused with fibroepithelial polyps, abscesses, warts, melanocytic lesions, and tumors. In conclusion, although the vulva is a small compartment, its developmental and histologic complexity can result in a variety of unusual and rare benign polypoid and papular lesions, some unique to the vulva, which might present diagnostic challenges to the clinicians and pathologists. In addition, many bear controversy regarding their histogenesis and origin of development in the vulva.     

Benign hepatocellular lesions and neoplasms: a comprehensive review

The prevalence of benign mass-forming liver lesions has significantly increased in recent years due to advances in diagnostic imaging. In general, these lesions can be either neoplastic or nonneoplastic and carry a different prognosis and management. Among benign mass-forming lesions of the liver, hemangiomas are the most common, followed by focal nodular hyperplasia, which is encountered ten times more frequently than adenomas. Hepatocellular adenomas are the third most common benign tumor of the liver. Their classification was revised in 2016 based on histomorphology and molecular signatures and includes hepatocyte nuclear factor-1 alpha (HNF1A)-mutated hepatocellular adenomas, beta-catenin 1 (CTNNB1) gene–mutated hepatocellular adenomas, interleukin-6 signal transducer gene–mutated or inflammatory/telangiectatic hepatocellular adenomas, and unclassified hepatocellular adenomas. Since then, a new subtype has been discovered, decreasing the proportion of unclassified cases. Hepatocellular adenomas have different molecular characteristics, behavior, and management, depending on the subtype. The telangiectatic subtype tends to bleed and may cause hemoperitoneum whereas the beta-catenin mutated subtype can progress to malignancy and is surgically resected independent of the size or symptoms. Other hepatic lesions include nodular regenerative hyperplasia, which occurs in the setting of blood flow alterations; and focal fatty change or benign steatotic nodules. Lastly, epithelioid angiomyolipomas are very uncommon benign mesenchymal liver tumors that belong to a family of tumor arising from perivascular epithelioid cells (PEComas) either sporadically or in the setting of tuberous sclerosis. Herein, we review these benign hepatic lesions and neoplasms and discuss the histomorphology and immunohistochemistry that allow us to render a specific diagnosis.     

Ovarian tumors and tumor-like lesions in the first three decades

The relative frequency of ovarian tumors and tumor-like lesions that occur in young females (defined in this article as up to 30 years of age) differs considerably from that seen in older patients. The spectrum of lesions encountered is reviewed, with emphasis on those disproportionately seen in younger patients, particularly primitive germ cell tumors, certain tumors in the sex cord-stromal family, the distinctive tumor known as small cell carcinoma of hypercalcemic type, and selected tumor-like lesions. Comments are made initially on the relative frequency of the various well-known categories of ovarian neoplasia in the first three decades, compared to females overall, and differences within the first three decades are noted. Some of the more noteworthy of these include the occurrence of follicular cysts in neonates due to in-utero maternal stimulation, and the often large size of these lesions, with sometimes dramatic clinical manifestations; the relative rarity of the commonest germ cell tumor of the ovary, the dermoid cyst, in the very early years of life; the peak incidence of all primitive germ cell tumors in the mid to late teens and early 20s; the peak of small cell carcinoma of hypercalcemic type in the early 20s; the preponderance for the juvenile granulosa cell tumor to occur in the first two decades and for one distinctive form of Sertoli–Leydig cell tumor, the retiform variant, to peak at about 15 years of age; the occasional finding of mucinous cystic tumors, usually benign, in the teenage years, and their greater frequency than other surface epithelial neoplasms; a gradual increase in frequency of all types of surface epithelial neoplasia, but particularly mucinous tumors and serous tumors as patients move through the 20s; and the rarity of metastatic neoplasia in the first three decades in general, but with occasional dramatic examples such as some Krukenberg tumors being seen in these years, as may some of the distinctive tumors of the young such as neuroblastoma. Consideration of the gross and microscopic features, and differential diagnosis, of individual neoplasms follows the introductory remarks and emphasizes the importance of gross pathology. An example of the latter is the marked difference in most cases between a dermoid cyst and an immature teratoma, the former being dominantly cystic and the latter dominantly solid, and the latter on average twice as large as the former. Caution should be exercised in entertaining a diagnosis of immature teratoma if a lesion is grossly a typical dermoid cyst. The treacherous shared gross characteristics and age distribution of the dysgerminoma and small cell carcinoma of hypercalcemic type are noted. The rarity of monodermal teratomas and malignant neoplasms such as squamous cell carcinoma arising in dermoid cysts in the first three decades is noted. The distinctive features of two recently described stromal neoplasms, microcystic stromal tumor and luteinized thecomas of the type associated with sclerosing peritonitis, are emphasized as is the varied differential diagnosis of the juvenile granulosa cell tumor and Sertoli–Leydig cell tumor. Sections on ovarian tumors and tumor-like lesions in pregnant patients and tumor-like lesions overall conclude the article.     

A clinicopathologic study of tumors and tumor-like lesions of the penis

A total of 147 specimens from 93 patients with penile lesions were examined at Nagasaki University Hospital during a 27-year period from 1961 to 1987. The most frequent malignant tumor was squamous cell carcinoma (SCC, 33 cases, 35.5%), followed by extramammary Paget's disease, transitional cell carcinoma, and Bowen's disease. The benign tumors and tumor-like lesions included condyloma acuminatum, cyst of the genitoperineal raphe, and lymphangioma. SCC of the penis accounted for less than 0.1% of all specimens and less than 0.62% of malignant tumors in men filed at our hospital. True phimosis accompanied 81.5% of the SCC cases. The 5- and 10-year survival rates for SCC were 77.2% and 71.3%, respectively. Two patients died of penile SCC. It was considered that an absence of both keratohyaline granules in the granular layer and melanin pigment in the basal layer can serve as a useful histologic indicator for diagnosis of well differentiated SCCs that are otherwise difficult to identify.     

Testicular and paratesticular tumors and tumor-like lesions in the first 2 decades

The spectrum of testicular tumors and tumor-like lesions that affect young patients (defined for purposes of this article as less than 20 years old) differs significantly from that in an older age group. Although germ cell tumors remain the single largest category, they are a smaller proportion than in adults. Furthermore the pathogenesis and behavior of comparably named germ cell tumors differ depending on whether or not they have developed in prepubertal or postpubertal patients. This is most apparent for the teratomas, which are almost uniformly benign in children but, with some notable exceptions, malignant in the older patients. But even the most common malignant tumor of the testis in children, the yolk sac tumor, despite its identical morphology, lacks the association with other germ cell tumor types, including intratubular germ cell neoplasia, and more aggressive behavior that typify the adult tumors. Among the sex cord–stromal tumors, the juvenile granulosa cell tumor predominates in children, mostly occurs in those under 1-year old, and, for all intents and purposes, is not seen in the postpubertal period. It has a distinctive morphology and, to date, a uniformly benign outcome. There are additional tumors in the sex cord–stromal group that are mostly seen in young patients, including the large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia. The former is sometimes associated with the Carney syndrome and, to date, all of the latter with the Peutz–Jeghers syndrome. The subtypes of lymphomas and leukemias that involve the testis in children are rare in older patients, and similar remarks pertain to the metastatic tumors, where neuroblastoma (especially) and Wilms׳ tumor are most common but may be mimicked by primary tumors originating in the paratestis. The pseudoneoplastic lesion, the testicular “tumor” of the adrenogenital syndrome, is usually found in young patients and bears a strong resemblance to the Leydig cell tumor, although there are features that allow its distinction, which is important given its frequently bilateral nature and amenability to medical management through glucocorticoid administration. One of the preferential sites for embryonal rhabdomyosarcoma is the paratestis of young patients, where the spindle cell variant predominates. The melanotic neuroectodermal tumor (retinal anlage tumor) usually occurs in the first year of life, typically involves the epididymis, and uncommonly metastasizes. Occasional cases of the desmoplastic small round cell tumor present in the paratestis of teenagers, and some distinctive tumor-like lesions of the paratestis may also be seen, including meconium periorchitis and splenic–gonadal fusion (occupying both testis and paratestis). These tumors and tumor-like lesions and many others are discussed in this review with the hope it will provide the diagnostic pathologist aid in recognizing the lesions and providing some insight into their clinical significance.     

Gastrointestinal stromal tumors and other mesenchymal lesions of the gut.

In the past 5 years, there has been a paradigm shift in our understanding of gastrointestinal stromal tumors (GISTs). Once thought to be smooth muscle tumors, these uncommon neoplasms are now thought to differentiate along the lines of interstitial cells of Cajal, the pacemaker cells of the gut. Along with this understanding comes an exciting new drug therapy (Gleevec) that for the first time offers real hope to patients with malignant stromal tumors. Overall, approximately 60-70% of stromal tumors are from the stomach, 20-30% are from the small intestine, and <10% come from the esophagus, colon, rectum, omentum, and mesentery. Between 10 and 30% of GISTs are malignant. Stromal tumors should be studied in a site-specific fashion, as tumors from a given location in the gut have unique growth patterns and corresponding behaviors. Although the most important tool needed to diagnose a GIST is still a hematoxylin and eosin-stained section, a confirmatory CD117 stain is recommended (and may be required for drug therapy). True smooth muscle tumors, inflammatory fibroid polyps, fibromatoses, schwannomas, inflammatory myofibroblastic tumors, and solitary fibrous tumors all enter into the differential diagnosis of GISTs. This article reviews the histologic features of these tumors in the context of recent molecular genetic and immunohistochemical advances.     

Benign lesions mimicking malignant tumors of the esophagus

Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies.     

超声对睾丸肿瘤及肿瘤样病变的诊断及鉴别诊断

目的 探讨超声对睾丸肿瘤及肿瘤样病变的诊断及鉴别诊断价值.方法 回顾分析33例睾丸肿块患者的超声声像图表现,并与其病理结果进行对照.结果 33例睾丸肿块患者中,精原细胞瘤12例,淋巴瘤6例,表皮样囊肿6例,混合性生殖细胞瘤2例,畸胎瘤2例,胚胎性癌、内胚窦瘤各1例,其他3例.结论 超声检查对睾丸肿瘤及肿瘤样病变的诊断及鉴别诊断具有重要价值,可为进一步治疗方案的制定提供依据,是睾丸肿瘤首选的影像学检查方法.     

Benign mesenchymal tumors of the external ear: A series of 14 cases

Primary soft tissue tumors of the head and neck region are relatively uncommon. Most are not distinctive to this region. Benign mesenchymal tumors of the external ear are rare. Some are common tumors but unusual in this location. All of the reported cases were single case reports or small series. Our aim was to study the prevalence and spectrum of different types of benign mesenchymal tumors that involve the external ear in our institution, to find out whether any lesion is distinctive to this site, their potential clinical associations and to highlight their potential diagnostic challenges. We performed a retrospective review study over 13 years. We retrieved 14 cases of external ear tumors. They included two cases of leiomyomas, two hemangiomas, three neurofibromas, two xanthogranulomas, three osteomas, a lipoma and a sclerotic fibroma. The age range was between 8 and 61 years with an average age of 34.2 years. The male to female ratio was 1.3 to 1. The average size was 8 mm. They were miscellaneous uncommon lesions and most were not unique to the external ear. Meatal osteomas and auricular angioleiomyomas are not infrequent with some predilection to the ear. With the exception of neurofibromatosis type-1, they were solitary nonsyndromic lesions. Multiplicity can be a hint to a syndrome. Clinically, benign external ear mesenchymal tumors can be confused with neoplastic and nonneoplastic lesions. Histopathologic examination is needed for proper classification. Benign soft tissue tumors of the external ear are generally easy histologic diagnosis. Immunohistochemistry is needed to confirm the diagnosis in certain tumors showing overlapping features.