Rosai-Dorfman disease of the testis: an unusual entity that mimics testicular malignancy

A 47 year old Chinese man with diabetes mellitus and previously treated pulmonary tuberculosis presented with painless right testicular enlargement of 1 month's duration. He underwent an orchidectomy for presumed testicular neoplasm corroborated clinicoradiologically. Histological examination of the testicular mass revealed an inflammatory lesion comprising lymphocytes, plasma cells and sheets of pale staining histiocytes, some containing lymphocytes within their ample cytoplasm, suggestive of emperipolesis. S100 immunohistochemistry stained the histiocytes, while ultrastructural examination confirmed emperipolesis. A diagnosis of Rosai-Dorfman disease was made, an exceedingly rare testicular lesion. Clinicoradiological findings mimicked a neoplasm, while the inflammatory histological appearances with occasionally discerned multinucleated cells raised the possibility of xanthogranulomatous orchitis. Tuberculous orchitis was excluded through negative Ziehl-Neelsen stains and PCR for mycobacterium, while seminoma, which sometimes features a predominant inflammatory component obscuring neoplastic cells, was excluded by absent immunostaining for placental alkaline phosphatase and CD117.     

Primary follicular lymphoma of the testis in childhood: an entity with peculiar clinical and molecular characteristics

BACKGROUND/AIMS: Paediatric primary follicular lymphoma of the testis (PPFLT) is exceptional: the few reported cases seem to lack BCL-2 gene rearrangement and/or protein expression. The aim of this study was to characterise a PPFLT arising in a 4 year old boy. METHODS: This case was characterised using conventional histological analysis, immunohistochemistry, and a polymerase chain reaction based method for the detection of immunoglobulin V(H) chain rearrangements. RESULTS: The neoplasm was staged I(E)/A; left orchiectomy and chemotherapy were performed, producing complete remission. Histology showed a predominantly follicular lymphoid infiltrate mainly composed of centroblast-like cells. The phenotype was CD20(+), CD79a(+), CD10(+), bcl-6(+), B cell specific activating protein(+), kappa light chain(+), CD30(-/+), interferon regulating factor 4(-/+), c-myc(-/+), lambda light chain(-), CD3(-), bcl-2(-), p53(-), cytokeratin(-), and placental alkaline phosphatase(-). Lymphomatous elements were found within a CD21(+) follicular dendritic cell network and 70% were positive for Ki-67/MIB-1. Molecular analysis revealed monoclonal immunoglobulin heavy chain gene rearrangement and BCL-6 mutations, in the absence of BCL-2 major breakpoint and BCL-2 minor cluster region rearrangements, p53 mutations, and death associated protein kinase gene hypermethylation. CONCLUSIONS: These findings suggest a different pathogenesis of PPTFL compared with adult follicular lymphoma and might explain its favourable course in spite of aggressive histology.     

The morphogenesis of adenocarcinoma of the cervix—a complex pathological entity

The cytological and histological features of 20 cases of adenocarcinoma of the cervix are presented of which 14 cases were in situ and two were microinvasive. The frequent association of atypia with malignancies of the cervical squamous epithelium is stressed. Abnormal reserve or stem cells were found in many of these cases. This study demonstrates the importance of the proper identification of these cells in cytological material and gives support to the theory that these cells play a role as a precursor cell to squamous and glandular neoplasms.     

Apocrine metaplasia: a new type of müllerian metaplasia.

Apocrine differentiation was an incidental finding in an ovarian cyst. This is considered to be a further example of Müllerian metaplasia that has not been described before and which, theoretically, could occur in any organ of Müllerian derivation (ovary, uterus, cervix or fallopian tube). It is suggested that sites of such metaplasia could in turn be the origin of primary apocrine carcinoma in any of the above locations.     

Serrated neoplasia of the stomach: a new entity

AIM: Despite the fact that gastric carcinoma continues to be one of the most common cancers world wide, only dysplasia in flat mucosa and adenomas have been shown to evolve into invasive carcinoma. The aim of this paper is to report a novel histological phenotype of gastric adenoma with early invasive growth. MATERIAL AND RESULTS: The patient presented with gastric complaints. A barium examination revealed an ulcerated tumour in the corpus, apparently infiltrating the gastric wall. The endoscopic examination showed a pediculated protruding tumour in the greater curvature. Punch biopsies were reported as invasive adenocarcinoma. Because of the poor condition of the patient, a partial gastrectomy was performed. The histological examination revealed elongated fronds with lateral crenated, saw tooth-like notches as a result of scalloped epithelial indentations. Areas with high grade dysplasia, with carcinoma in situ, and invasive carcinoma at the tip of the adenoma were demonstrated. The pedicle of the protruding neoplasia "emerged" from a non-protruding serrated adenoma. CONCLUSIONS: The protruding serrated neoplasia had apparently evolved from a non-protruding serrated gastric adenoma. This appears to be the first case of gastric serrated neoplasia in the literature.     

Malignant disease of the pleura: a histopathological study with special emphasis on diagnostic criteria and differentiation from reactive mesothelium

In order to define the histopathological criteria for the diagnosis of malignant neoplasm involving pleura, we studied 11 pleurectomy specimens containing undoubted malignant cells. The most important feature for a diagnosis of malignancy was the pattern of neoplastic infiltration of the fibrous sub-pleural tissue. These criteria were subsequently applied in a re-analysis of 76 pleural needle biopsies with a diagnosis of cancer. The patterns most frequently seen were a multi-pronged growth of at least four clusters of atypical cells in the fibrous sub-pleural tissue, a solid pattern with a large collection of atypical cells and a confluent one where large numbers of small clusters of atypical cells appeared almost fused in the stroma. Less frequently, malignant cells covered the surface of fibromuscular tissue, or were found in an intravascular or intramuscular location, but often associated with any of the three main patterns. Five needle biopsies were considered suspicious and 11, considered benign, contained a prominent mesothelial reaction. The benign control cases showed mesothelial cells mainly in a peripheral growth pattern or as clusters of cells interspersed with fibrin, without any mitotic activity; granulation tissue and lympho-histiocytic infiltrates were more frequently seen in the control group.     

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.     

Adenoid cystic carcinoma of the prostate: case report on a rare entity and review of the literature

Adenoid cystic carcinoma is an unusual histological variant of prostatic carcinoma. Because of its rarity, the natural history of this tumor is not known. Here we report this rare entity in a 62-year-old man who presented with symptoms of urinary tract obstruction. Digital rectal examination and ultrasonography (USG) showed an enlarged hard nodular prostate. Serum prostate-specific antigen (PSA) and prostatic acid phosphate levels were found to be within the normal range. Transrectal ultrasound-guided 12 core biopsies of prostate showed morphological features of an adenoid cystic carcinoma in 8 cores (bilateral, mid and base) on histopathological examination. Immunohistochemistry performed for PSA on paraffin section was negative. After diagnosis, bilateral orchidectomy was performed, and hormonal therapy was started in the form of androgen receptor blocker. The patient was clinically stable during a limited follow up of six months.     

Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult patients with signs of maldevelopment of the testis

Based on a well established association between testicular cancer and undescended testis and more recent publications on epidemiological links between these disorders and male infertility, we proposed the existence of a testicular dysgenesis syndrome (TDS). In most cases TDS presents with impaired spermatogenesis, only in rare cases the full range of its signs, including genital malformations and testicular cancer can be seen in one patient. In order to further corroborate our hypothesis about the presence of testicular dysgenesis in patients with testicular abnormalities, we decided to re-analyse recent testicular biopsies derived from patients with infertility, hypospadias and undescended testis. We searched for histological signs of testicular dysgenesis: microliths, Sertoli-cell-only tubules, immature seminiferous tubules with undifferentiated Sertoli cells, and tubules containing carcinoma in situ (CIS) cells. We identified 20 patients who fulfilled the histological criteria for testicular dysgenesis, 9 of whom were diagnosed with uni- or bilateral testicular germ cell neoplasia, and the remaining ones with subfertility. The presence of CIS was detected in 5 patients (3 of them with overt contralateral germ cell tumours). In all but one of the CIS cases, at least one additional sign of testicular dysgenesis was detected. Clinical records of all patients were subsequently analysed. The majority of cases had oligozoospermia or azoospermia. Their reproductive hormone profiles correlated with the results of semen sampling and testicular histology. In conclusion, our study of 20 patients with various reproductive abnormalities provided evidence that TDS is a real clinical entity. We speculate that most of these abnormalities are caused by adverse environmental effects rather than specific gene mutations.     

Müllerian adenosarcoma of the uterine body: a report of nine cases

Nine cases of Mullerian adenosarcoma of the uterine body, first defined in 1974 by Clement & Scully, are described. The tumour usually occurs in elderly women and appears macroscopically as a polypoid mass filling the uterine cavity. Histologically these neoplasms are characterized by having a benign epithelial component set in a sarcomatous stroma. The epithelial element consists of tubular glands, cystically dilated glands and a surface epithelium. The glandular and surface epithelium usually resembles that of proliferative endometrium but may be of mucinous type and can undergo squamous metaplasia. Occasional mitotic figures, multilayering and intraluminal tufting are seen in the actively growing but benign glands which are considered to be an integral component of the tumour. The sarcomatous stroma contains spindle cells, round cells and, less frequently, multinucleated giant cells and rhabdomyoblasts. The Mullerian adenosarcoma represents a relatively benign variant of the mixed mesenchymal sarcoma of the uterus and is probably more common than is generally realized. Myometrial invasion is rarely deep and the majority of patients with this neoplasm survive. Vaginal recurrence occurs only in a minority of patients and distant metastasis is exceptional.     

Keratin 10‐positive orthokeratotic dysplasia: a new leucoplakia‐type precancerous entity of the oral mucosa

Kobayashi T, Maruyama S, Abé T, Cheng J, Takagi R, Saito C & Saku T
(2012) Histopathology  61, 910–920 Keratin 10‐positive orthokeratotic dysplasia: a new leucoplakia‐type precancerous entity of the oral mucosa Aims: We investigated a group of oral mucosal lesions with characteristic hyperorthokeratotic foci, which we termed orthokeratotic dysplasia (OKD), to determine if it could be identified as a distinct histopathological entity. Methods and results: We screened 282 surgical specimens from 200 patients with oral leucoplakia‐type squamous cell carcinoma (SCC) or carcinoma in situ (CIS). OKD was defined as an oral mucosal lesional focus in which hyperorthokeratosis was predominant in the presence of the granular cell layer. A total of 84 OKD foci from 62 cases found among the 200 SCC/CIS cases were analysed. According to its rete ridge shapes, OKD was classified into three subtypes: flat (14.3%), leg (63.1%) and intermediate (22.6%). Eighty per cent of OKD foci were adjacent to the main foci of SCC or CIS, and they were demarcated sharply from each other. Most of the OKD constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. Numbers of Ki‐67‐positive cells in the first basal layer were greater in OKD than in normal epithelia. Conclusions: The findings indicate that OKD is a distinct variant of epithelial dysplasia related to malignancies, and hence that it is important to recognize its existence.     

Chordoid glioma of the third ventricle: confirmatory report of a new entity.

The term "chordoid glioma" was recently introduced to denote a circumscribed, apparently low-grade neoplasm arising in or preferentially involving the third ventricle of middle-aged women. We report biopsy and postmortem findings in a 60-year-old woman with symptoms of forgetfulness, headache, and lethargy. Neuroimaging showed a contrast-enhancing third ventricular mass with obstructive hydrocephalus. The tumor was subtotally resected. Microscopically, it consisted of clusters and strands of epithelioid cells in a mucoid matrix. Its margins were remarkably discrete and showed little tendency to infiltrate surrounding brain parenchyma. The majority of neoplastic cells were glial fibrillary acidic protein (GFAP) and vimentin positive, whereas S100 protein labeled only individual cells. Stains for epithelial membrane antigen (EMA) and cytokeratin were nonreactive. There was no evidence of neuroendocrine differentiation or expression of estrogen and progesteron receptors. Lymphoplasmacellular infiltrates were noted throughout the lesion and at the tumor-brain interface. The MIB-1 labeling index averaged 1.5%. At present, chordoid glioma is considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features.     

Malignant mixed Müllerian tumor (homologous type) of the adnexa with neuroendocrine differentiation: a case report.

Malignant mixed müllerian tumors (MMMT) are unusual neoplasms occurring mostly in the uterus. In the ovary, they are very rare and represent fewer than 1% of all ovarian malignancies; in the salpinx, they are even rarer than those of the ovary. We report a carcinosarcoma of the left adnexa having features of neuroendocrine differentiation in a 69-year-old female. The tumor contained both adenocarcinoma and squamous cell carcinoma having dear cell change admixed with an undifferentiated malignant mesenchymal component. The sarcoma components consisted of spindle cells, small-round cells and bizarre giant cells mimicking rhabdomyoblast. Almost all of the carcinomatous glandular components and some foci of the squamous cell and undifferentiated carcinomatous components were focal positive for S-100 protein, chromogranin, neuron specific enolase, synaptophysin and Leu-7. Electron microscopy revealed membrane-bound neurosecretory granules in the cytoplasm of some glandular epithelial cells. Histologically, the tumor involved the left adnexa, abdominal peritoneum, surface of the bladder dome, omentum and left external iliac lymph node (stage IIIc).     

Leydig cell differentiation during maturation of the rat testis: a stereological study of cell number and ultrastructure

In an effort to further understand the basis for the changes in steroidogenesis known to occur during sexual maturation in the rat, we examined by quantitative morphologic methods the number and ultrastructure of Leydig cells in fetal rats (days 18-20 of gestation) and in rats from days 2 to 3 of age through adult. Quantitative light microscopic analyses indicated that Leydig cell number, when expressed per unit volume of testis, was very high in fetal rat testes, fell significantly in testes of days 2 to 3 rats, and subsequently rose significantly. When Leydig cell number was expressed per testis rather than per unit volume of testis, the results indicated that testes of fetal rats and rats of days 2 to 3 contained the same number of Leydig cells; after the neonatal period, significant increases in Leydig cell number per testis occurred in concert with increases in testis weight. Quantitative electron microscopic studies revealed significant differences in the ultrastructure of fetal and adult populations of Leydig cells. For example, Leydig cells of fetal and neonatal rats contained abundant lipid, whereas Leydig cells of weeks 7 to 8 and adult rats contained little. Stereological analyses also revealed dramatic changes in smooth endoplasmic reticulum and inner mitochondrial membrane surface areas during sexual maturation, both per cell and per testis. These findings are discussed with respect to the steroidogenic capacity of the testis during sexual maturation.     

Sunflower seed husk agar: a new medium for the differentiation of Candida dubliniensis from Candida albicans

A sunflower (Helianthus annuus) seed husk agar medium has been developed and evaluated for differentiation of Candida dubliniensis from Candida albicans on the basis of colony morphology and chlamydospore production. All C. dubliniensis isolates (n=40) produced rough colonies with hyphal fringes and abundant chlamydospores whereas 101 of 105 (96.2%) C. albicans isolates produced smooth colonies with no evidence of chlamydospore production. Since this medium is free from oil droplets, chlamydospores can be examined with greater clarity by Dalmau plate technique. This medium provides a simple and cost-effective tool for the presumptive differentiation of C. dubliniensis from C. albicans and is particularly suited for clinical microbiology laboratories where biochemical or molecular methods for the differentiation of these two species are not available.     

Lymphangioma of the kidney: a pathologic entity distinct from solitary multilocular cyst.

A case of primary renal lymphangioma is reported. This represents the first documented example of such a lesion confirmed by immunocytochemical and ultrastructural studies. Whereas previously regarded as synonymous terms, the recognition of lymphangioma as a pathologic entity distinct from solitary multilocular cyst of the kidney appears warranted. Although rare, lymphangioma should be considered in the differential diagnosis of multicystic lesions of the kidney.