EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Polymorphism 1558 C > T in the aromatase gene (CYP19A1) in low-grade endometrial stromal sarcoma.

Low-grade endometrial stromal sacomas (ESS) are estrogen-sensitive tumors. Polymorphic variation in the CYP19 gene can affect estrogen synthesis by increasing aromatase activity resulting in elevated levels of estrone and estradiol. We examined the polymorphism 1558 C > T in he aromatase gene (CYP19A1) in a series of 20 low-grade endometrial stromal sarcomas. Archival formalinfixed and paraffin-embedded material was analyzed with a fast real-time PCR system. The homozygous C/T- and the homozygous mutant T/T-genotypes were detected in 10/20 (50%) and 7/20 (35%) samples, respectively. Polymorphism 1558 C > T in the aromatase gene may represent a high-risk allele with increased local estrogen levels.

High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma--report of two cases.

BACKGROUND: Endometrial stromal sarcomas (ESS) are rare uterine tumors with unknown etiological risk factors, but estrogen-dependent growth promotion. CASES: We present two patients with advanced ESS, who had increased levels of p,p-DDE; hexachlorobenzene; PCB 28; PCB 52; PCB 101; PCB 138; PCB 153 and PCB 180 in abdominal adipose tissue. Other xenoestrogens were within expected limits for the non-exposed European population. CONCLUSION: Increased levels of xenoestrogens in patients with ESS may be involved in the pathogenesis of ESS. Chronic exposure to xenoestrogens may be a risk factor for tumor progression.

Intermediate filament cytoskeleton of amnion epithelium and cultured amnion epithelial cells: expression of epidermal cytokeratins in cells of a simple epithelium.

Using immunofluorescence microscopy and two-dimensional gel electrophoresis, we compared the cytoskeletal proteins expressed by human amnion epithelium in situ, obtained from pregnancies of from 10-wk to birth, with the corresponding proteins from cultured amnion epithelial cells and cultures of cells from the amniotic fluid of 16 week pregnancies. Epithelia of week 16 fetuses already display tissue-specific patterns of cytokeratin polypeptides which are similar, although not identical, to those of the corresponding adult tissues. In the case of the simple amnion epithelium, a complex and characteristic complement of cytokeratin polypeptides of Mr 58,000 (No. 5), 56,000 (No. 6), 54,000 (No. 7), 52,500 (No. 8), 50,000 (No. 14), 46,000 (No. 17), 45,000 (No. 18), and 40,000 (No. 19) is present by week 10 of pregnancy and is essentially maintained until birth, with the addition of cytokeratin No. 4 (Mr 59,000) and the disappearance of No. 7 (Mr 54,000) at week 16 of pregnancy. In full-term placentae, the amnion epithelium displays two morphologically distinct regions, i.e., a simple and a stratified epithelium, both of which express the typical amnion cytokeratin polypeptides. However, in addition the stratified epithelium also synthesizes large amounts of special epidermal cytokeratins such as No. 1 (Mr 68,000), 10 (Mr 56,500), and 11 (Mr 56,000). In culture amnion epithelial cells obtained from either 16-wk pregnancies or full-term placentae will continue to synthesize the amnion-typical cytokeratin pattern, except for a loss of detection of component No. 4. This pattern is considerably different from the cytokeratins synthesized by cultures of cells from amniotic fluids (cytokeratins No. 7, 8, 18, and 19, sometimes with trace amounts of No. 17) and from several so-called "amnion epithelial cell lines." In addition, amnion epithelial cells in situ as well as amnion epithelial cell cultures appear to be heterogeneous in that they possess some cells that co-express cytokeratins and vimentin. These observations lead to several important conclusions: In contrast to the general concept of recent literature, positively charged cytokeratins of the group No. 4-6 can be synthesized in a simple, i.e., one-layered epithelium. The change from simple to stratified amnion epithelium does not require a cessation of synthesis of cytokeratins of the simple epithelium type, but in this case keratins characteristic of the terminally differentiated epidermis (No. 1, 10, and 11) are also synthesized.(ABSTRACT TRUNCATED AT 400 WORDS)

Epithelial origin of cutaneous anchoring fibrils.

Anchoring fibrils are essential structural elements of the dermoepidermal junction and are crucial to its functional integrity. They are composed largely of type VII collagen, but their cellular origin has not yet been confirmed. In this study, we demonstrate that the anchoring fibrils are primarily a product of epidermal keratinocytes. Human keratinocyte sheets were transplanted to a nondermal connective tissue graft bed in athymic mice. De novo anchoring fibril formation was studied ultrastructurally by immunogold techniques using an antiserum specific for human type VII procollagen. At 2 d after grafting, type VII procollagen/collagen was localized both intracellularly within basal keratinocytes and extracellularly beneath the discontinuous basal lamina. Within 6 d, a subconfluent basal lamina had developed, and newly formed anchoring fibrils and anchoring plaques subjacent to the xenografts were labeled. Throughout the observation period of the experiment, the maturity, population density, and architectural complexity of anchoring fibrils beneath the human epidermal graft continuously increased. Identical findings were obtained using xenografts cultivated from cloned human keratinocytes, eliminating the possibility of contributions to anchoring fibril regeneration from residual human fibroblasts. Immunolabeling was not observed at the mouse dermoepidermal junction at any time. These results demonstrate that the type VII collagen of human cutaneous anchoring fibrils and plaques is secreted by keratinocytes and can traverse the epidermal basal lamina and that the fibril formation can occur in the absence of cells of human dermal origin.

Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma.

We report a case of a 9-cm mixed epithelial and stromal tumour of the kidney in an obese 70-year-old woman with diabetes. The ovarian-type stroma had a spindle cell component that was positive for progesterone receptors and had the hitherto unreported presence of abundant foci of luteinised stromal cells with characteristic immunohistochemical positivity to alpha-inhibin, calretinin, aromatase and gonadotropin-releasing hormone (GnRH) receptors. We conclude that the stromal component is identical to ovarian cortical stroma. We believe that ovarian-type stroma occurs in extragenital tumours as a result of an epithelial-stromal interaction in an environment of hormonal hyperstimulation.

[Clinical experiences using the Versajet system in burns: indications and applications]. / Klinische Erfahrungen mit dem Versajet-System in der Verbrennungsbehandlung - Indikationen und Anwendungen.

Early debridement and early skin grafting are the "Gold standard" in the surgical treatment of burns. There are different debridement methods available. Concerning the treatment of burns, surgical-sharp debridement, laser ablation and hydrosurgery system are used. While in full thickness burns the sharp debridement is advisable, the Versajet shows its benefits in the treatment of partial thickness burns. Especially for debridement of difficult to treat areas - face, neck, lips, fingers, interdigital spaces, convex and concave areas the Versajet System shows its benefits. With the Versajet System, tissue excision is precise; moreover it helps to avoid the damage of viable tissue and its vascular supply.

Survey of adjuvant hormone therapy in patients after endometrial stromal sarcoma.

INTRODUCTION: We surveyed the use of adjuvant hormonal therapy in patients with endometrial stromal sarcomas. MATERIAL AND METHODS: A questionnaire was circulated among the 130 members of an Internet-based endometrial stromal sarcoma support group. The questions pertained to age at diagnosis, organs involved at diagnosis, recurrences, metastases, current disease status, and treatment protocols, with special focus on hormonal therapy. RESULTS: The questionnaire was returned by 64 of 120 women (49%). At the time of the study 48 patients (mean follow-up 2.4 (range, 1-9) years) had no evidence of disease (NED) and 16 (mean follow-up 6.2 (range, 1-22) years) were alive with disease (AWD). Of the 16 women AWD, 15 (95%) were being treated with hormones as opposed to ten of 48 (21%) women with NED. Hormone treatment consisted of progestins (15 patients), aromatase inhibitors, aromatase inhibitor plus GnRH analog], or tamoxifen. DISCUSSION: Adjuvant hormonal therapy presently appears to be used predominantly in women with advanced or recurrent endometrial stromal sarcomas but is also a potential option for patients after surgery without residual tumor.

Recurrent endometrial stromal sarcoma after treatment with high-dose chemotherapy and autologous stem-cell support: A case report.

INTRODUCTION: The efficacy of high-dose chemotherapy plus transplantation of autologous hematopoetic stem cells in patients with endometrial stromal sarcomas is unknown. CASE REPORT: A 39-year-old woman with Stage III endometrial stromal sarcoma (ESS) underwent radical surgery, followed by five courses of ifosfamide, adriamycin and dacarbazine postoperatively. Six months after primary surgery stem cell priming was performed. Five months later bone marrow was aspirated and high-dose chemotherapy with carboplatin, vepeside and holoxan were administered after which bone marrow was retransfused. Seven years after primary surgery the patient developed an abdominal recurrence which was removed surgically and adjuvant radiotherapy was administered. One year later the patient underwent hemicolectomy because of a new recurrence infiltrating the ascending colon. Treatment with 25 mg exemestane was begun. The patient is currently alive and free of disease nine years after the initial diagnosis. CONCLUSION: Aggressive chemotherapy with autologous stem-cell support seems to be ineffective in patients with ESS.

Endometrial stromal sarcoma--observational evidence of a genetic background?

BACKGROUND: Endometrial stromal sarcomas (ESS) constitute only 0.2% of all gynecological malignancies, and risk factors or genetic associations are largely unknown. We are in contact with more than 100 patients with ESS via an internet support group, and our aim was to analyze the personal and familial medical histories of this large patient group for possible familial cancers aggregations in ESS patients. METHODS: A questionnaire regarding the personal and familial medical history was circulated among the members of the internet group, which was returned by 64 patients. RESULTS: At diagnosis of ESS the average age was 42 years. Fifty percent had a history of long-term hormonal treatment. One patient each had a previous history of breast carcinoma, thyroid cancer and cutaneous malignant melanoma. One familial case of ESS was observed. At least one malignancy in the family was reported by 47% of patients, and the mother or father were affected in 26%. Multiple familial cancers were observed in 25% of ESS patients. The most frequent familial cancer was breast cancer (25%) followed by endometrial (8%), lung (7%) and prostate carcinoma (5%). CONCLUSIONS: Patients are young, report hormonal treatments and have a familial history of hormone-dependent carcinomas. This suggests a strong genetic predisposition in the oncogenesis of ESS. Patients with ESS may suffer from an inherited genetic predisposition similar to familial breast and prostate carcinoma which may render them susceptible to hormone-dependent growth promotion and/or to cellular damage from particular estrogen metabolites of endometrial cells resulting in a ESS.

Cultured porcine epithelial grafts: an improved method.

An improved method of in vitro cultivation of porcine keratinocytes by which keratinocyte sheets suitable for grafting can be generated rapidly is described. Epidermis from split-thickness porcine skin is enzymatically separated from dermis with 0.25% Dispase solution (37 degrees C) within 3 h, and trypsinized to a single cell suspension. Keratinocytes are grown in Dulbecco-Vogt modified Eagle medium supplemented with 20 ng/ml hydrocortisone, 100 micrograms/ml penicillin, 100 micrograms/ml streptomycin, and 20% (cells from six-month-old pigs) or 10% fetal calf serum (cells from two-month-old pigs). Freshly isolated keratinocytes are plated at a density of 1.25 X 10(6) cells/ml since their plating efficiency is about 15 times lower than that of human keratinocytes grown under comparable conditions. Primary keratinocytes plated on plastic grow to confluence faster than those plated on lethally irradiated 3T3-J2 feeder layer cells. Porcine keratinocytes grown on plastic reach senescence in the third passage but, when subsequently cultivated on a lethally irradiated 3T3-J2 feeder layer, can be passaged up to seven times. Nevertheless, plating efficiency of second-passage porcine keratinocytes is only about 5%-7%, whereas that of human newborn foreskin keratinocytes is 20%-30%. Confluent stratified primary cultures grown on plastic, or secondary cultures grown on feeder layers, are used for grafting. The sheets are detached with Dispase solution and stapled to vaseline gauze to facilitate handling. Epidermal regeneration from porcine grafts produced by this method has been demonstrated after transplantation to full-thickness wounds excised to muscle fascia in donor animals.

Cultured keratinocyte sheets enhance spontaneous re-epithelialization in a dermal explant model of partial-thickness wound healing.

An in vitro model for partial-thickness cutaneous wound healing is described in which the influence of variables present in vivo, such as blood-borne factors and inflammatory cells, is eliminated. Dermal sheets of porcine skin are maintained in culture at the air-liquid interface in serum-free medium, and re-epithelialization from the keratinocytes of the hair infundibula can be studied. Dermal sheets of different thicknesses harvested from various depths were first evaluated for viability and regenerative potential in serum-supplemented medium. Mid-dermal explants, 20/1000 inch thick, showed the greatest epithelial outgrowth from the appendigeal keratinocytes and the longest viability in vitro. Explants of this type were used in all subsequent experiments. The effects of growth factors on re-epithelialization of the explants were studied in a serum-free environment. Epidermal growth factor, cholera toxin, bombesin, and insulin-like growth factor alone and in various combinations were applied to the explant surface in aqueous solutions by micropipette. Outgrowth was assessed by computerized morphometric analysis (RS/1 program by BBN) at days four and eight. Among all factors tested, cholera toxin alone and in combination with insulin-like growth factor produced the greatest epithelial outgrowth. Nevertheless, topical applications of growth factors failed to induce complete re-epithelialization within the experimental time frame. In contrast, explants to which cultured human keratinocyte sheets were topically applied regenerated a confluent and regularly stratified epidermis within 6 d.

Evidence of fetal microchimerism in Hashimoto's thyroiditis.

Fetal microchimerism, the engraftment of fetal progenitor cells into maternal tissues, has been implicated in the etiology of autoimmune diseases. We used PCR analysis to determine whether microchimerism occurred in the thyroid glands of female patients suffering from Hashimoto's disease and thus may be involved in its etiology. PCR amplification was performed from thyroid gland specimens using primers unique to a Y-chromosomal sequence (SRY gene) and primers for a sequence that is Y/X-chromosomal homologous except for a 6-bp deletion in the X-chromosomal sequence (amelogenin). Microchimerism was detected in 8 of 17 Hashimoto patients, but in only 1 of 25 controls (nodular goiters). Both groups were of similar age and had comparable numbers of pregnancies and numbers of sons. All individuals with microchimerism had given birth to at least 1 son. Our results show that microchimerism is significantly more common in Hashimoto patients than in patients suffering from nodular goiter. We therefore suggest that microchimerism might play a role in the development of Hashimoto's disease, although we cannot completely eliminate the hypothesis that microchimerism is just an "innocent bystander" in a process triggered by other mechanisms.

CK7 expression in carcinomas of the Waldeyer's ring area.

Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing squamous cell carcinomas (SCC). Their cervical lymph node metastases are not uncommonly cystic and filled with necrotic tumor cells. Some cysts, however, contain clear fluid. During the investigation of SCC producing "fluid-filled" cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90 primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of primary and metastatic carcinoma with special focus on the expression of CK7, a putative marker for ductal differentiation. CK7 was expressed in submucosal minor salivary gland acini and ducts, but not in the squamous surface epithelium of the Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts of submucosal minor salivary glands, and showed only insignificant surface involvement. They were characterized by a solid infiltrative growth pattern of basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7-positive carcinomas produced CK7-positive cystic nodal metastases, most of which contained paucicellular fluid. No solid CK7-positive nodal metastases were identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring area appear to arise from large excretory ducts of submucosal minor salivary glands with only limited surface involvement, express CK7, and produce CK7-positive cystic "fluid-filled" nodal metastases. The histomorphology and immunophenotype suggest that these carcinomas represent basaloid SCC arising from excretory ducts of the submucosal minor salivary glands.

Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease.

Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered to be idiopathic cutaneous palisading granulomatous dermatitides. There are sporadic reports of such lesions occurring in patients with coexistent systemic diseases other than diabetes mellitus. Having encountered 49 patients whose skin biopsies showed GA or NL lesions in the setting of extracutaneous disease, the authors set out to assess their clinical and histopathological findings to determine if any parameters were predictive of underlying systemic disease. Fifty-two skin biopsies from 49 patients having either GA or NL in whom there was a clinical history of an associated systemic disease were analyzed by light microscopy. The main systemic disease associations were rheumatologic, endocrine, hematologic, infectious, and inflammatory bowel diseases, ANCA positive vasculitic syndromes, and sarcoidosis. The clinical and histomorphological features were compared with those of a control group of patients whose skin biopsies showed GA or NL and in whom there was no history of extracutaneous disease. For the systemic disease group, patients were selected either retrospectively or prospectively from 160,000 cases accessioned in a 24-month period in the dermatopathology databases of Pathology Services, Inc (Cambridge, MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease cases from the former service were analyzed blindly by the second author and from the latter service were analyzed blindly by the first author. Patients in the control group were obtained retrospectively from the Pathology Services Inc. database by the authors. The location of the lesions was atypical in 30 of 34 biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22 biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients with NL tissue reactions in the systemic disease group showed an atypical location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The clinical diagnostic considerations were much broader in the systemic disease group versus the control group and included vasculitis, panniculitis, and connective tissue diseases including morphea in the former. In 22 of 34 GA biopsies and 16 of 18 NL biopsies from the systemic disease group, an active vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was demonstrable. None of the GA or NL biopsies from the control group showed a similar active vasculopathy. An active vasculopathy was predictive of systemic disease in patients having either a GA-like or an NL-like tissue reaction (P < .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies and 2 of 9 NL (P = .33) biopsies in the control group. The finding of an active vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction, particularly in the setting of an atypical clinical presentation both with respect to the location and appearance of lesions, should prompt consideration of an underlying systemic disease, as should extravascular neutrophilia in a skin biopsy showing a GA-like tissue reaction.

Lateral neck cysts--the branchial theory revisited. A critical review and clinicopathological study of 97 cases with special emphasis on cytokeratin expression.

Theories regarding the origin of lateral neck cysts (LNC) range from congenital branchial pouch abnormalities to acquired salivary gland inclusions within lymph nodes. We analyzed 97 LNC histologically and evaluated their cytokeratin (CK) profile in a search for their derivation. 77/97 LNC were located in soft tissues, 20/97 within lymph nodes. LNC of young patients and of recent symptomatic presentation in older patients were lined by respiratory epithelium with scant lymphoid tissue, with expression of "simple epithelial" CK in ciliated cells and bimodal expression of "simple" and "stratified-epithelial-type" CK in basal cells. In longer standing symptomatic LNC, respiratory epithelium alternated with transitional-type pseudostratified epithelium with intraepithelial Langerhans cells and lymphoid hyperplasia, or consisted exclusively of squamous epithelium. We propose that respiratory epithelium is the "native" epithelium of LNC and squamous metaplasia results from inflammation induced stem cell hyperplasia in respiratory epithelium, evidenced by co-expression of "simple" and "stratified-epithelial-type" CK in all cells of transitional-type pseudostratified epithelium, the early stage in metaplastic transformation. Respiratory epithelium predominates in early LNC, lines pharyngeal tonsils and the recessus tonsillo-tubalis, and is a minor constituent of palatine tonsil but is not present in salivary glands. None of the LNC contained dysplasia, atypia, or carcinoma, or were associated with a primary carcinoma of tonsils or head and neck. We demonstrate that LNC arise from developmental remnants (congenital) of the 2nd branchial pouch, which may lie dormant for many years. Symptomatic enlargement, squamous metaplasia and lymphoid hyperplasia ensue as a consequence of immunologic stimulation a development reflected in hyperplastic palatine tonsils.

Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A clinicopathological analysis of 14 cases.

We present 14 patients with primary sinonasal melanomas (SM) identified from 1984-1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.