Apocrine cystadenoma: A long-standing apocrine hidrocystoma with an adenomatous proliferation.

BACKGROUND: Apocrine cystadenoma is a rare, benign adenomatous cystic neoplasm, the pathogenesis of which is not fully understood. We sought to characterize the clinical, dermatoscopic, and histopathologic features of apocrine cystadenoma and its relationship to hidrocystoma. METHODS: We retrospectively analyzed cases of apocrine cystadenoma and hidrocystoma retrieved from the dermatopathology laboratory information system. RESULTS: Of the 350 cases apocrine cystic lesions, 13 cases of apocrine cystadenomas met the inclusion criteria. The age ranged from 20 to 84 years with an average of 64 years. They were long-standing (duration 3-15 years), slow-growing, large tumors usually found on the scalp. Dermatoscopy accentuated translucent light to dark blue color and prominent vessels that were present more at the periphery. All lesions were multilocular with columnar to cuboidal lining and decapitation secretion. A large portion of the lesion consisted of a simple nonproliferative epithelial lining, identical to that observed in apocrine hidrocystomas, while the proliferative adenomatous component made up a smaller portion with two patterns: (1) tubular proliferation, which either protruded into the cystic cavity or expanded outward peripherally, or (2) papillary projections, which were multiple layers thick with fibrovascular core, sometimes accompanied by tubular proliferation. Immunohistochemical stains showed strong staining for p40 and a sparse number of cells stained for Ki-67 and p53. CONCLUSIONS: The long duration of the lesion and the large areas of simple apocrine epithelial lining suggest that apocrine cystadenomas arise from long-standing apocrine hidrocystomas. However, the retrospective nature of the study from a single institution is a limitation.

A Paratesticular Multicystic Tumor of the Tunica Vaginalis Testis as Rare Paratesticular Cystadenoma.

The cystadenoma of the testis and paratestis arising from an unequivocal oviduct-like structure, which is morphologically almost identical with those of the ovarian surface epithelium. These are very rare benign tumors of young adults. They present as asymptomatic cystic lesions. Bilateral paratesticular cystadenomas are strongly associated with von Hippel-Lindau syndrome and correlate with infertility. It is a neoplasm with low malignant potential. Most cystadenomas are benign but a few cases of malignant transformation of embryonic remnants have been reported in the appendix testis, including cases of adenocarcinoma, cystadenocarcinoma, and a low malignant müllerian-type epithelial tumor. We report the rare case of a 63-year-old man with a paratesticular multicystic cystadenoma of the male adnexa without association to von Hippel-Lindau disease.

The Morphologic Spectrum of Sertoliform Cystadenoma of the Rete Testis: A Series of 15 Cases.

Sertoliform cystadenoma of the rete testis (SCRT) is rare with only 9 cases reported to date in the literature, none with follow-up. Four large genitourinary pathology consult services were searched. We identified 15 cases of SCRT. Men were 21 to 84 years old (mean, 46 y) and had testicular discomfort or mass. Other findings were seminoma (n=1), spermatocele (n=2), hydrocele (n=1), varicocele (n=1), and scrotal hematoma (n=1). Eight had preoperative serum tumor markers, which were normal. Tumors ranged from 0.3 to 4 cm (mean, 1.5 cm). All of them were well circumscribed with solid and cystic features and occupied on average, 73% of the rete (20% to 100%). The tumors were mostly confined within dilated channels of the rete testis and showed classic features consisting of: (1) tubules with well-formed lumina in 87% of cases; (2) well-formed tubules with no lumina in 87% of cases; and (3) cords/nests in hyalinized or myxoid stroma in 73% of cases. Other patterns included: (1) solid/sheet growth in 26% of cases; (2) individual cells in 13% of cases; (3) festoons in 13% of cases; (4) branching tubules in 7% of cases; and (5) papillary in 7% of cases. Cells were cuboidal with round to oval nuclei with small nucleoli, except at the periphery where projections into rete tubules had a more columnar appearance. In the festooning pattern, nuclei were pseudostratified and columnar with prominent nucleoli and nuclear grooves. In 4 cases, tumor extended into adjacent seminiferous tubules surrounded by dense peritubular fibrosis, with in some cases small cysts lined by flattened epithelium containing pale lightly granular material. All cases lacked necrosis and significant atypia. Mitoses ranged from 0 to 2 per 10 high-power field. Follow-up ranged from 4 to 170 months with mean of 97 months. For the 13 cases with information, all patients were alive, except for 3 who died of either unrelated causes (9.2 and 10 y) or of unknown cause (4.8 y at age 89 y). We performed immunohistochemistry for steroidogenic factor 1 and inhibin in 4 of our cases, where 3 (75%) were positive for both markers. We also describe 2 additional cases which morphologically resembled SCRT but had more atypical features. This study highlights that SCRT has variable morphology. We also verify the benign nature of the lesion and its lack of association with any syndromes.

Novel Hormone Receptors Present in Apocrine Cystadenoma of the Eyelid.

A 53-year-old woman presented with an apocrine cystadenoma of the right upper eyelid. Histologic examination revealed proliferating epithelial cells with apocrine snouts and occasional mitotic figures. Immunohistochemical analysis revealed a Ki-67 index of 15% and positive staining for synaptophysin, chromogranin, estrogen receptor, progesterone receptor, gross cystic disease fluid protein (GCDFP)-15, and mammoglobin. The complement of positive immunomarkers in this case reinforces the importance of total excision and careful histologic assessment.

A Comparative Study of Immunohistochemical Myoepithelial Cell Markers in Cutaneous Benign Cystic Apocrine Lesions.

The use of immunohistochemical markers for myoepithelial cells (MEC) is a useful tool in the distinction of benign from malignant epithelial neoplasms. Although their use in breast tumors is well recognized, little is known concerning its application in comparable cutaneous lesions. Using benign cutaneous cystic apocrine lesions as a study model, the aim of this study was to compare 5 immunohistochemical markers [calponin, p63, smooth muscle actin (SMA), cytokeratin 14, and CD10] in their effectiveness to highlight MEC. Cases of apocrine hidrocystoma and cystadenoma (n = 44) were reviewed with a particular emphasis on proliferative features and apocrine change. The MEC staining pattern and the intensity and distribution scores in proliferative (n = 29) and nonproliferative (n = 15) lesions were assessed, and the differences between the 2 groups were statistically analyzed using Fisher exact test. Calponin and SMA stained MEC in the most consistent manner. Being a nuclear stain, p63 was easy to interpret but typically showed discontinuous staining. Cytokeratin 14 not only effectively highlighted MEC but also stained some luminal epithelial cells in an unpredictable manner. Because of prominent background dermal fibroblast staining, CD10 was often difficult to interpret. Only SMA and p63 showed a statistically significant difference in MEC staining intensity scores between the proliferative and nonproliferative groups. Our results show that immunohistological staining for MEC in benign cystic apocrine lesions of the skin is variable. The authors recommend that a panel of markers that includes calponin and p63 be used and highlight the need for awareness of specific caveats associated with individual markers.

Esophageal submucosal gland duct adenoma: a clinicopathological and immunohistochemical study with a review of the literature.

Esophageal submucosal gland duct adenoma (ESGDA) is a rare tumor. The clinicopathological features of the ESGDA and its precursor lesion have not been comprehensively evaluated. In this study, we aimed at delineating the clinicopathological features of the ESGDA and cyst formation of the esophageal submucosal gland duct (ESGD), as well as their correlations and clinical implications. We identified three cases of ESGDA and 16 cases of cyst formation of the ESGD among 786 endoscopic mucosal resection specimens over a 7-year period. The median patient age was 58 years with a male predominance. These lesions were small submucosal bulges locating at the lower esophagus with a size no more than 1 cm. The main microscopic changes of these lesions included content retention, multilayered epithelium or papillary folds of the ESGD and inflammatory cell infiltration, acidophilic degeneration, hyperplasia or atrophy of the acini. The included cases generally showed moderate to severe microscopic esophagitis. The ESGDA was mainly consisted by multiple glandular cysts covered by two layers of cells. Immunohistochemical results showed that the luminal duct lining cells and basal cells were positive for CK7 and p63, respectively. Both of the two layer cells were positive for HMWCK and negative for CK20, p53, CDX2, MUC5AC, MUC6, MUC2 and MUC1. The proliferation index was very low (1%). The diagnostic criteria of the ESGDA were proposed and, the differential diagnosis was discussed. Cyst formation of the ESGD is considered to be the precursor lesion of the ESGDA, because they have overlapping clinicopathological features with progressive relationship. In addition, the ESGDA have close connection with advance of the GERD and, probably, an increased risk of carcinoma.

"Apocrine Hidrocystoma and Cystadenoma"-like Tumor of the Digits or Toes: A Potential Diagnostic Pitfall of Digital Papillary Adenocarcinoma.

Digital papillary carcinoma (DPC) is a rare, underreported, and often misdiagnosed malignant tumor of the sweat glands. It is often located on the digits and toes and most commonly occurs in male individuals in their fifties to seventies. Because of lack of pain, slow growth, and an inconspicuous appearance, clinical diagnosis is often missed or delayed. In contrast, apocrine hidrocystoma (AH) is a cystic adenoma that arises from the apocrine secretory coil, and it is extremely rare for AHs to develop on the digits. We report 7 cases of DPC, including clinical course, histopathologic and immunohistochemical findings, and therapeutic approach in which the initial histopathologic diagnosis in all cases was AH or cystadenoma. However, complete excision of the neoplasms led to a final diagnosis of DPC. After an adequate treatment, no recurrence or metastasis was found in any of the cases described. All the cases studied showed similar histopathologic and immunohistochemical findings. The initial incisional biopsy showed large unilocular or multilocular cystic spaces situated within the dermis, lined by a double layer of epithelial cells with tiny papillary structures. No cellular atypia, necrosis, or pleomorphism was observed. However, complete excision revealed neoplastic lesions involving the dermis and/or subcutis, with an infiltrative pattern and papillary projections into luminal spaces. Immunoperoxidase studies showed positivity for CK7, S-100 protein, CEA, p63, smooth muscle actin, and calponin. DPC is a rare but life-threatening malignancy, therefore it is important to be able to identify such a lesion both clinically and histopathologically, treat it, and monitor the patient for the tumor's potential recurrence and metastasis. Pathologists and dermatopathologists should be aware that a histopathologic diagnosis of AH or cystadenoma on the fingers and toes should be established with caution, because probably those lesions represent the superficial and cystic component of an underlying DPC, and a wider excision should be performed.

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts. As the cysts increase in size, they fuse forming larger cysts. Later lesions demonstrate a unilocular cyst lined by predominantly acinar epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic connotation, does not seem to accurately reflect the histologic, immunohistochemical, or molecular features of these lesions. We suggest readopting the term "acinar cystic transformation" until the non-neoplastic versus neoplastic origin of these lesions can be resolved.

Sertoliform cystadenoma: a rare benign tumour of the rete testis.

Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335.

Basal cell cystadenoma of the lacrimal gland: diagnostic pitfalls of a basaloid pattern in lacrimal tumours.

An 85-year-old male experienced a painless swelling along the left lateral orbit for one year. A computed tomography scan demonstrated a cystic mass in the orbit adjacent to the lacrimal gland. There was a concern for malignancy considering the large size and the patient's age, so the tumour was excised. Histopathology of the tumour showed nests with basaloid patterns, but a definitive diagnosis was not rendered. The uncertainty of tissue diagnosis coupled with the basaloid pattern, which carries a grim prognosis in some salivary gland tumours, led us to refer this case to an authority on lacrimal gland pathology, who suggested that this tumour be called a basal cell cystadenoma. To the best of our knowledge, a basal cell cystadenoma of the lacrimal gland has not been reported in the literature. We present histopathological features that distinguish this tumour from malignant tumours with a basaloid pattern. We also discuss the management differences associated with basaloid patterns in lacrimal tumours.

Palpebro-orbital apocrine cystadenoma: immunohistochemical verification of a unique variant with a critical differential diagnosis.

PURPOSE: To describe a unique apocrine cystadenoma of the superonasal eyelid and anterior orbit. METHODS: Clinical evaluation with axial and coronal CT; histopathologic and immunohistochemical studies including sections stained with hematoxylin-eosin, periodic acid Schiff, alcian blue, mucicarmine, and Prussian blue for iron; and monoclonal antibodies against cytokeratin-7, epithelial membrane antigen, smooth muscle actin for myoepithelial cells, gross cystic disease fluid protein-15 for apocrine differentiation, and CD-68 and lysozyme for histiocytes. RESULTS: The cyst possessed a multilaminar lining composed of polygonal to low cuboidal cells. A stalk of solid tumor ingrowth from the wall was composed of adenomatous units of eosinophilic cells with apical snouts ("decapitation secretion"). No goblet cells were discovered. Both the cyst's lining cells and the adenoma expressed gross cystic disease fluid protein-15 indicative of apocrine differentiation. The adenoma displayed inner adlumenal cells that were CK-7 and epithelial membrane antigen positive, and outer myoepithelial cells that were smooth muscle actin positive. Simple local excision was curative. CONCLUSION: This unique lesion is the first example in the ophthalmic and dermatopathologic literatures of a solid adenoma encompassed by an apocrine cyst, which more typically features short or blunt papillae. It must be distinguished from other eyelid and/or anterior orbital cystic lesions including eccrine hydrocystomas; classical and extratarsal dermoid cysts; congenital and acquired conjunctival cysts and dermoids; dacryocystocoeles/mucoceles; canaliculops and lacrimal gland dacryops; and congenital cystic odontogenic choristomas.

Cystadenoma of the palate: immunohistochemistry of mucins.

Cystadenoma is a relatively rare benign epithelial tumor of the salivary glands, and described herein is an additional case. A 51-year-old Japanese man had noticed a mass of the left hard palate 25 years previously. Macroscopically, the resected specimen was a multicystic lesion. Histologically, the tumor was composed of bilayered columnar epithelium with cystic change and partial solid growth of glandular structures with clear cells. The tumor cells had mild cellular atypia, but the tumor lacked papillary growth and a fibrous capsule. Immunohistochemistry was positive for cytokeratins, epithelial membrane antigen, MUC1, MUC4 and MUC6, but negative for myoepithelial markers, MUC2, MUC5AC and MUC5B. Such MUC expression patterns suggested that cystadenoma occurs from excretory ducts.

Expression of survivin is associated with malignant potential in epithelial ovarian carcinoma.

Survivin is a new member of the inhibitor of apoptosis family of anti-apoptotic proteins. It has been reported that survivin is expressed during fetal development and in cancer tissues. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression of survivin in human endometrial carcinomas. We analyzed serial frozen sections for survivin protein expression in 26 patients with ovarian epithelial carcinoma and 10 patients with benign cystadenoma of the ovary by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of survivin-stained cells and the characteristics of the patient including histological classification, clinical stage, histological grade, and clinical outcome. Survivin was weakly detected in some benign ovarian cystadenomas (0-12.1%). There was, however, abundant survivin immunoreactivity in the nucleus and/or cytoplasm of the epithelial ovarian carcinoma cells. Scoring on the basis of the percentage of positive cells indicated that survivin expression was significantly associated with PCNA-labeling index, clinical stage, histological grade, clinical outcome, and survival rate (p<0.01, respectively). We conclude that the survivin protein is a defining diagnostic marker for epithelial ovarian carcinomas that may also yield prognostic information.

Acinar cystadenoma of the pancreas: a previously undescribed tumor.

A 58-year-old diabetic woman died as a result of an acute myocardial infarction caused by coronary atherosclerosis and thrombosis. A 9 cm multiloculated cystic lesion was found incidentally in the body and tail of the pancreas. The microcysts and locules were lined by one or two layers of normal-appearing acinar cells. In some locules there were clusters of acinar structures containing eosinophilic material. The cuboidal cells lining the locules had morphologic and immunohistochemical features of acinar cells. The lesion was interpreted as an acinar cystadenoma, the benign counterpart of the well-established acinar cystadenocarcinoma of the pancreas. Acinar cystadenoma should be included in the differential diagnosis of cystic tumors of the pancreas.

Sialadenoma papilliferum of the hard palate: report of 2 cases and immunohistochemical evaluation.

This study reports on the clinical and histologic features of 2 previously unreported cases of sialadenoma papilliferum. Immunohistochemical analysis of one of the cases demonstrated that the ductal cell component shows both epithelial and myoepithelial differentiation.

Expression of p57/Kip2 protein in pancreatic adenocarcinoma.

INTRODUCTION: Evaluation of the biologic character of carcinomas requires understanding of cell cycle regulators. AIMS: To investigate p57 expression in human pancreatic adenocarcinoma and cyst adenoma. METHODOLOGY: We examined the expression of p57(Kip2), a member of the Cip/Kip family, in 45 pancreatic adenocarcinomas, 7 cystadenomas, and 7 chronic pancreatitis cases. RESULTS: The p57 labeling index (LI) in duct epithelia in chronic pancreatitis averaged 32.8+/-8.3 and was significantly higher than in normal duct epithelia (18.8+/-6.6; p = 0.0011). For the carcinoma, the LI averaged 46.0+/-20.9, which was significantly higher than that for normal duct epithelia (p < 0.0001) and cystadenoma (16.0 11.2; p = 0.0007). However, it was significantly reduced in cases with stage IV disease (p = 0.0351), lymph node metastasis (p = 0.0003), larger size (p = 0.0094), capsular invasion (p = 0.0462), lymphatic invasion (p = 0.0351), and cell proliferating activity (p = 0.0002). In multivariate analysis, p57 LI in pancreatic adenocarcinoma was independently linked to high proliferating activity (p = 0.0230). CONCLUSION: These results suggest that p57 plays a role in the hyperplastic change of the ducts in chronic pancreatitis and that pS7 overexpression contributes to the downregulation of cell proliferation, and its decreased expression contributes to the progression of pancreatic adenocarcinoma.

Cystadenoma of the seminal vesicle: report of a case with ultrastructural findings.

Cystadenomas of the seminal vesicles are extremely rare benign tumours. We have not been able to find more than 10 cases in the literature. A benign cystadenoma of the seminal vesicle is described in a 49-year-old man. The clinical presentation, gross appearance, microscopic characteristics, immunohistochemical and ultrastructural findings of this uncommon tumour are discussed. The purpose of this paper is to report an unusual case of cystadenoma of the seminal vesicle and review the 10 previously reported cases in the English literature.

Oncocytic cystadenoma of the parotid gland with tyrosine-rich crystals.

A case of benign oncocytic cystadenoma with abundant intraluminal tyrosine-rich crystals involving the parotid gland is described.

Expression of the imprinted H19 oncofetal RNA in epithelial ovarian cancer.

STUDY: To examine the expression of the imprinted maternally expressed H19 gene in benign, low malignant potential (borderline) and malignant surface epithelial ovarian tumors. DESIGN: In situ hybridization for H19 RNA using S-labeled and digoxigenin-labeled probes was performed on paraffin sections of ovarian surface epithelial tumors. The serous tumors included nine section cystadenomas, twelve serous tumors of low malignant potential and twenty serous carcinomas, grade I-IIII (FIGO classification). A smaller group included two mucinous cystadenomas, four mucinous tumors of low malignant potential and two mucinous cystadenocarcinomas. RESULTS: H19 expression was found to be positive in 6/9 (67%) serous cystadenomas, 9/12 (75%) of serous tumors of low malignant potential and 13/20 (65%) of invasive serous carcinomas. Expression in mucinous tumors was confined to the stroma beneath the epithelial lining. CONCLUSION: H19 is expressed in the majority of serous epithelial tumors. Taking into consideration the high percentage of H19 expressing serous ovarian neoplasms we suggest that H19 RNA may be used as an adjuvant tumor marker for the diagnosis and mainly for staging and follow-up of patients with serous ovarian carcinoma.