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Basement membrane laminin and type IV collagen in various benign and malignant adnexal tumors of the skin: an immunohistochemical study.

Thirty benign and seven malignant adnexal tumors of the skin and one lymph node metastasis were stained for laminin and type IV collagen with rabbit antibodies against the human basement membrane (BM) proteins using the immunoperoxidase technique. Fifteen of the benign sweat gland, sebaceous gland, and hair follicle tumors showed a continuous and distinct BM around the tumor aggregates. The cylindromas and eccrine spiradenomas seemed to produce excessive amounts of BM material, part of which was seen as amorphic patches within the tumor cell clusters, whereas the trichofolliculomas, trichoepitheliomas, and pilomatrixomas showed an absence of BM from many areas. In syringomas, in addition to the tubular structures surrounded by a continuous BM, undifferentiated cell nests containing granular BM material were present. They probably represent primitive structures obtaining during early development into tubules. The seven malignant tumors and the only metastasis studied here all contained small, narrow strips of BM material extracellularly between the infiltrating tumor clusters. Only in two cases was faint staining for laminin found within the cells. The pepsin pretreatment of the formalin-fixed, paraffin-embedded samples had most probably degraded the intracytoplasmic BM material in most cases. The BM defects were found to be associated with malignancy and low differentiation of the adnexal skin tumors, as reported previously for other tumor types, but a partial loss of BM was also associated with high differentiation in some benign adnexal tumors.

Adenoma↗

Extramammary Paget's disease--a proliferation of adnexal origin?

AIM: To investigate a possible follicular origin of extramammary Paget's disease (EPD). EPD is a predominantly intraepidermal tumour with extensive involvement of adnexal structures and high recurrence rates suggesting a follicular stem cell origin. Cytokeratin (CK) 15 and CK19 are considered markers for follicular stem cells located in the hair follicle bulge region. METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues of 12 cases of primary EPD (three anal, nine vulvar) were studied immunohistochemically with antibodies to CK15 and CK19. All cases of EPD showed polygonal Paget cells in the interfollicular epidermis, hair follicles, sebaceous and apocrine glands distributed individually, in nests and in gland-like areas. The polygonal Paget cells were intimately associated with small, flat, mitotically active, 'compressed' keratinocytes. The large Paget cells uniformly expressed CK19 in 12/12 EPD. The small 'compressed' keratinocytes showed strong cytoplasmic CK15 staining in 9/12 EPD with focal accentuation, while the polygonal Paget cells were negative. CONCLUSIONS: These histological and immunohistochemical observations allow the following conclusions: (i) the small, flat, 'compressed' keratinocytes are an integral part of EPD; (ii) the dual cell population is reminiscent of sebaceous glands with mature sebocytes and germinative keratinocytes; (iii) since both cell types express cytokeratins typical for follicular differentiation, EPD may be a proliferation of adnexal stem cells residing in the infundibulo-sebaceous unit of hair follicles and adnexal structures.

Aged↗

Microcystic adnexal carcinoma treated by microscopically controlled excision.

Microcystic adnexal carcinoma is a distinct clinicopathologic entity with combined pilar and eccrine differentiation. Clinically it resembles other adnexal neoplasms, but it tends to be deeply invasive and locally aggressive. A 47-year-old man with microcystic adnexal carcinoma of the left cheek with deep dermal and subcutaneous invasion was successfully treated by microscopically controlled excision. The possible etiologic association with teenage radiation therapy is discussed.

Adolescent↗

Microcystic adnexal carcinoma. Ten cases treated by Mohs micrographic surgery.

BACKGROUND: Microcystic adnexal carcinoma is a slow-growing, nondescript, locally aggressive, deeply infiltrating neoplasm histologically characterized by an infiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction, keratin-filled cysts, and glandular structures. OBJECTIVE: Microcystic adnexal carcinoma is uncommon and may be mistaken microscopically for other benign and malignant entities. Perineural or intraneural involvement by tumor cells is characteristic and extension into underlying structures including muscle, fat, and bone are frequently encountered. Although local recurrences are common after standard surgical excision, metastases have not been reported. Extensive resections of lesions may be necessary to extirpate widespread tumor, particularly those that are long standing or recurrent. Because significantly increased morbidity is associated with recurrent disease, surgical and histopathologic techniques that stress examination of all margins are advantageous. METHODS: We review the course of 10 patients with microcystic adnexal carcinoma of the face (six primary and four recurrent lesions) and their treatment by Mohs micrographic surgery.

Adult↗

The origin of the adnexal tumors of the skin: a viewpoint.

Histogenesis of adnexal tumors of the skin has not been the subject of an independent study or a publication since the theory of pluripotentiality of epithelial matrix cells was introduced and applied to the origin of adenxal tumors some 25 years ago. In this period, a number of new tumor entities have been described. Histologic studies as well as enzyme histochemistry, electron microscopy and, lately, the results Of the application of monoclonal antibodies have provided a wealth of new information. In this article a review of the histogenesis of adnexal tumors is made and, based on clinical and histologic data provided, an alternative view for origin of adnexal tumors of the skin is proposed.

Cell Transformation, Neoplastic↗

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival.

BACKGROUND: The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS: The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS: At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS: Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.

Adolescent↗

Long term outcome of ocular adnexal lymphoma subtyped according to the REAL classification. Revised European and American Lymphoma.

AIM: To classify ocular adnexal lymphomas according to the Revised European and American Lymphoma (REAL) classification and to determine any correlation between clinical features or histomorphological variables with the patients' outcome. METHODS: Conventional and immunohistology were performed on representative sections of 53 specimens of 46 patients with ocular adnexal lymphoma. The antibodies used were CD20, BCL-2, CD21, CD23, CD43, CD3, CD5, p53, cyclin D1, pan-cytokeratin, kappa, lambda, IgD, and IgM. The growth fraction of the tumours was determined using the MIB-1 antibody directed against the Ki-67 antigen. Clinical follow up data regarding the outcome were obtained from the treating physicians and/or hospital files. The Student's t test and log rank test were used for statistical analysis. RESULTS: The patient collective consisted of 29 females and 17 males with an age range of 32-89.7 years (average 63 years). Almost all specimens represented B cell non-Hodgkin's lymphomas: extranodal marginal zone lymphoma (EMZL) (n=38), diffuse large cell B cell lymphoma (n=8), lymphoplasmocytic lymphoma/immunocytoma (n=2), mantle cell lymphoma (n=2), follicle centre lymphoma (n=1), and plasmacytoma (n=1). One case of a secondary anaplastic large cell lymphoma of T cell type (T-ALCL) was diagnosed. The majority of the patients had stage I disease. A variety of therapeutic regimens was administered, the main form of treatment being radiotherapy. The average follow up time was 85 months. Complete remission was achieved in 24 patients (10 after excision alone, eight after radiotherapy alone, three after combined excision and radiotherapy, one after chemotherapy alone, and two after combined radiotherapy and chemotherapy). 12 patients died of causes related to lymphoma; in one patient the cause of death was unknown. Six patients had persistent tumour at final follow up and two patients were lost to follow up. The stage at presentation, as well as the lymphoma malignancy category, had a significant correlation with the final course of the disease (p=0.0001 and p=0.03, respectively). A significant correlation was also noted between the final outcome (p<0.05) and tumour cell expression for Ki-67 antigen and p53 protein. CONCLUSION: 67% of patients with ocular adnexal lymphoma had EMZL. The stage at presentation had a significant influence on the final outcome. MIB-1 and p53 expression by the tumour cells proved to be important immunohistochemical markers concerning the prognosis. It is suggested that, following thorough staging investigations, primary EMZL (stage I) (if accessible) should be treated with excisional biopsy and subsequent low dose radiotherapy. Primary diffuse large cell B cell lymphoma of the ocular adnexa requires at least similar therapeutic measures and regular intensive follow up.

Adult↗

Loss of heterozygosity at cylindromatosis gene locus, CYLD, in sporadic skin adnexal tumours.

AIM: The gene for familial cylindromatosis (CYLD) has been localised to chromosome 16q, and has recently been cloned. Loss of heterozygosity (LOH) at 16q has also been demonstrated in sporadic cylindromas. The aim of this study was to investigate whether CYLD plays a role in the development of other skin appendage tumours. METHODS: A total of 55 cases of skin adnexal tumours, comprising 12 different types, and a control group of 14 squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) were studied. Three microsatellites (D16S407 (16p), D16S304 (16q), and D16S308 (16q)) were analysed for LOH after microdissection from paraffin wax embedded sections using laser capture microdissection. RESULTS: In keeping with previous data, a proportion of cylindromas exhibited LOH at markers on 16q, but not at 16p. The skin adnexal tumours showing a similar pattern included apocrine hydrocystomas, eccrine spiradenomas, and sebaceous adenoma. One case of syringoma showed LOH at 16q, and a further case at 16p, but not 16q. One case of eccrine hydrocystoma showed loss at 16p, but not 16q. The remaining tumours were either negative or non-informative. All tumours in the control group were either negative or non-informative, except for a single case of BCC showing LOH at 16q. CONCLUSION: CYLD may be involved in the development of skin adnexal tumours other than cylindromas.

Adenoma↗

Adnexal masses in pregnancy.

With the widespread use of routine abdominal ultrasound examination during pregnancy, adnexal masses are observed with increasing frequency. Most patients are clinically asymptomatic at the time of presentation, and most of the adnexal masses detected during early pregnancy disappear during the first 16 weeks of pregnancy. Ovarian tumors are estimated to occur in about 1 in 1,000 pregnancies and of these 3% are malignant. Here we present an overview about frequency, diagnostic procedures and pathological characteristics of these ovarian tumors. Moreover, current modalities for treatment during pregnancy are summarized. Surgical treatment of the adnexal masses has to be performed with adequate staging and debulking equal to the treatment of non-pregnant women. However, whereas during organogenesis abortion has to be considered prior to chemotherapy, later in pregnancy surgical debulking as complete as possible, followed by taxol-platinum chemotherapy is indicated. If the fetus is not viable at the time of primary surgery, neoadjuvant chemotherapy and complementation of surgery after delivery of the baby should be performed. It should be stressed that chemotherapy for ovarian cancer applied during pregnancy appears to be safe. However, no studies have evaluated the long-term consequences for children exposed to intra-uterine chemotherapy. Aspiration of cysts should be avoided, as the correlation between the histological evaluation of an ovarian malignancy and the cytological evaluation of aspirates is poor. Moreover, spillage of malignant cysts is hazardous for the patient.

Antineoplastic Combined Chemotherapy Protocols↗

Subspecialty adnexal ophthalmological examination using telemedicine.

We studied the clinical outcome of examination of a group of patients with adnexal (eyelid and orbit) conditions. Seventeen patients with adnexal problems were assessed by an ophthalmologist at a distance using telemedicine, and then subsequently by an ophthalmologist in a face-to-face consultation. Measurements such as palpebral aperture, levator muscle function and eyelid skin crease position were recorded. The clinical outcomes from both consultations were recorded independently by the consultants and then compared. The study showed that certain adnexal conditions, such as congenital and involutional ptosis, could be accurately assessed using telemedicine, but that other conditions, such as socket problems in patients who had a previous enucleation or those with non-specific ocular pain with less clear-cut features, were better assessed in a face-to-face consultation. Overall, teleconsultations appeared to be suitable for the assessment of uncomplicated ptosis but not for less well defined conditions. Other factors, such as family dynamics and language problems, also limited the usefulness of the technique.

Communication Barriers↗

Fluorescence in situ hybridization (FISH) analysis of primary ocular adnexal MALT lymphoma.

BACKGROUND: It remains unknown whether primary ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a homogeneous entity, as there are few reports of the results of cytogenetic or molecular analyses of these tumors. METHODS: We performed interphase fluorescence in situ hybridization (FISH) analysis to detect translocations and aneuploidy in 34 cases of primary ocular adnexal MALT lymphoma, and reviewed the histopathological findings. Correlations between the results of FISH analysis, the histopathological features and the clinical data were also analyzed. RESULTS: Among the 34 cases, FISH analysis revealed t(14;18)(q32;q21) in one case, trisomy 3 in 21 cases (62%), and trisomy 18 in 16 cases (47%). The cases with trisomy 18 had significantly more prominent lymphoepithelial lesions (LELs) and less nodularity in the tumors. In regard to the clinical correlations, tumors with trisomy 18 were observed predominantly in females and younger patients; also, in the majority of the cases, the tumor was of conjunctival origin. All the cases with recurrence showed trisomy 18 in the tumor. CONCLUSION: Primary ocular adnexal MALT lymphoma is a significantly heterogeneous entity. Cases with trisomy 18 may have unique clinicopathological features.

Adolescent↗

[Tumor marker CA-125 in adnexal inflammatory tumors].

BACKGROUND/AIM: The glycoprotein of a high molecular weight CA-125, which is not a specific tumor marker of ovarian cancer, is secreted by the endothelial cells of most pelvic organs. Endometriosis, inflammatory processes in the pelvic cavity, as well as some nongynecoligical malignant diseases, could be followed by the increased values of CA-125. Serial assessment of the values of CA-125 makes it possible to avoid surgical treatment, and, by means of the used conservative treatment, to avoid malignant diseases not to be noticed. METHODS: The study included 57 female patients hospitalized due to inflammable adnexal tumors. Besides following the values of serum CA-125 during and after the therapy, also performed were the transvaginal Doppler ultrasonography and the determination of the values of resistance index (RI). RESULTS: In 27 patients (55.1%) the CA-125 values ranged from 38.8 U/ml to 794 U/ml, while in 30 of the patients they were within the range of normal. In this group of the patients, besides the increased values of CA-125, also increased were the values of leucocytes (11(9)/1-20(9)/1), as well as the sedimentation rates (65-120) within the first hour. In all the 57 patients, transvaginal Doppler ultrasonography revealed the presence of adnexal tumor of inflammatory kind. The measured values of RI were within the range of 0.539-0.681. Eight of the patients were treated by the conservative--triple antibiotic therapy, while in 49 patients explorative laparotomy was performed. Hystorectomy was done in 12 of the patients, and one-side adnexectomy in 37 of them. CONCLUSION: The method for the assessment of CA-125 is simple and available which facilitates the monitoring of surgical, conservative or the combined therapy that is particularly significant in younger patients with inflammable adnexal tumor developed on the basis of endometrosis.

Adult↗

Combined microcystic adnexal carcinoma and squamous cell carcinoma arising in the ovarian cystic teratoma--a brief case report.

Malignant transformation of mature cystic teratoma of the ovary can develop with an incidence of 1-2%. Squamous cell carcinoma is the most common malignant tumor arising in benign cystic teratoma. The authors have recently experienced a case of combined microcystic adnexal carcinoma and squamous cell carcinoma arising in a benign cystic teratoma of the ovary in a 72-year-old Korean woman. The right ovarian cystic mass had been ruptured and firmly adhered with salpinx and omental fat tissue on operation. Thickened cystic wall with yellowish white solid infiltrative lesion was noted grossly, and two different malignant tumors of microcystic adnexal carcinoma exhibiting both eccrine and hair follicular differentiation and squamous cell carcinoma were observed microscopically. PAS and CEA positivities suggested eccrine differentiation in areas of microcystic adnexal carcinoma.

Aged↗

Adnexal masses during pregnancy: accuracy of sonographic diagnosis and outcome.

We sought to determine the accuracy of sonographic diagnosis and perinatal outcome in pregnancies with maternal adnexal masses. All patients with a prenatal sonographic diagnosis of an adnexal mass measuring 4 cm or greater beyond 12 weeks of gestation were identified. Only masses associated with live fetuses, for which pathologic follow-up or direct visualization of the ovary was available at a single hospital, were included in the study. Sonographic evaluation of the pelvic mass was done prospectively at the time of the original scan and characterized on the basis of morphologic criteria. One hundred and twenty-five pregnant patients 21 to 47 years old with 131 lesions formed the study group. The pathologic diagnoses included 40 dermoids, 15 endometriomas, 14 cysts, 13 cystadenomas, nine tubal cysts, four fibroids, and one ovarian cancer. Six patients had complex pathologic lesions and five had unusual diagnoses. Twenty-four patients had normal ovaries on follow-up examination. Sonographically benign appearing lesions were seen in 89.3% of patients. Ninety-five percent of dermoids, 80% of endometriomas, and 71% of simple cysts were characterized correctly. Fourteen of the 131 lesions (10.7%) had sonographic characteristics suggestive of malignancy. One of these 14 patients (7%) had ovarian cancer. This represents a 0.8% malignancy rate among the total number of lesions. Twenty-four of the 125 patients (19%) underwent second trimester laparotomy at the discretion of their managing obstetricians, with no pregnancy losses. One patient had acute torsion of a dermoid at 39 weeks. Prenatal sonography can accurately characterize maternal adnexal lesions.

Adult↗

Ocular-adnexal lymphoid tumors: a clinicopathologic and molecular genetic study of 77 patients.

PURPOSE: To determine whether molecular genetic analysis of ocular-adnexal lymphoid tumors, combined with histopathology and tumor location, is helpful in predicting which patients will develop systemic lymphoma. METHODS: A combined retrospective and prospective study of 77 patients with ocular-adnexal lymphoid tumors was performed. The tumors were subdivided into conjunctival, orbital, and eyelid lesions, and all were studied using both routine histopathology and molecular genetic analysis. RESULTS: Most lesions (70%) were small cell lymphomas of the mucosa-associated lymphoid tissue type, and the majority of tumors (90%) contained monoclonal or oligoclonal populations of lymphocytes discovered on molecular genetic analysis. Additionally, 72% of tumors exhibiting clonality had more than one gene rearrangement. Fifty-three percent of patients developed extraocular lymphoma sometime during the course of their disease. Patients with gene rearrangements on Southern blot hybridization had a 52% incidence of nonocular disease, compared with 63% of those without rearrangements. Patients with conjunctival tumors had a 37.5% incidence of nonocular disease, those with orbital tumors had a 54% incidence, and those with eyelid tumors had a 100% incidence of nonocular lymphoma. Only two patients died as result of systemic lymphoma. CONCLUSIONS: Most ocular-adnexal lymphoid tumors are lymphomas of the mucosa-associated lymphoid tissue type. The majority of tumors exhibit gene rearrangements on molecular genetic analysis, and this technique was not helpful in predicting which patients would develop nonocular lymphoma. Tumor location did have predictive value: Conjunctival lesions had the lowest incidence of nonocular lymphoma, and lid lesions had the highest incidence. Even with disseminated disease, most patients have a favorable prognosis with treatment.

Adult↗

Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma.

PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison. RESULTS: The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.

Adult↗

[Histopathology studies on 8,673 cases of ocular adnexal hyperplastic lesions and tumors].

OBJECTIVE: To study the histopathologic classification of ocular adnexal hyperplastic lesions and tumors according to the histogenesis and the anatomic sites. METHOD: To analyze retrospectively the pathologic specimens of 8,673 cases of ocular adnexal hyperplastic lesions and tumors between 1961 - 1997. RESULTS: There were 7,265 benign cases (83.77%), and 1,408 malignant cases (16.23%). Classification by anatomic sites: eye lid 5,313 cases (61.26%), orbit 1,484 cases (17.11%) and epibulbar 1,876 cases (21.63%). Classification by histogenesis: (1) Primary tumor 6,679 cases: epitheliogenic 2,481 cases (37.15%), mesenchymal 753 cases (11.27%), lympho-hematopoietic 102 cases (1.53%), neurogenic 1,542 cases (23.09%), congenital abnormal embryogenetic 1,767 cases (26.46%), uncertain resource tumor 34 cases (0.50%). (2) Secondary tumor 13 cases; (3) Metastatic tumor 9 cases; (4) Non-tumor lesion 1,972 cases. CONCLUSION: The classification is helpful to the histopathologic diagnosis and the study about the detailed distribution of common ocular adnexal hyperplastic lesions and rare tumors, and it also increases the pathologic diagnostic data in North China.

Eyelid Neoplasms↗

Laparoscopic management of adnexal masses. Safety and effectiveness.

OBJECTIVE: To evaluate the effectiveness and safety of the laparoscopic approach to adnexal masses. STUDY DESIGN: Sixty-one patients who underwent laparoscopic intervention due to various types of adnexal masses between March 1997 and April 1999 in a teaching hospital were assessed retrospectively. Patients with strong evidence of advanced ovarian cancer, such as large masses, ascites or omental cake, were excluded. Frozen section was performed intraoperatively, if indicated. In cases of malignancy, laparotomy was performed. RESULTS: Mean operation time was 67.2 minutes; average hospital stay was 1.2 days. Cyst enucleation was performed in 34% of patients. Two of 61 patients were diagnosed as having malignant disease and converted to laparotomy. Chemical peritonitis was encountered after dermoid cyst removal due to spillage of contents in spite of using an endobag and irrigating copiously with saline. No other complications were seen. CONCLUSION: Laparoscopy is a safe approach to adnexal masses and may decrease the rate of unnecessary laparotomies for benign cysts, which give no suspicious ultrasonographic signs.

Adult↗