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However blood pressure ranges for athletes discount 10 mg plendil, morphea shows a characteristic infiltrate of lymphocytes disposed along thickened collagen bundles and conspicuous sclerosis heart attack test buy discount plendil 10 mg on line, whereas lipodermatosclerosis always shows areas of fibrosis. At an ulcerated stage, the absence of a diffuse infiltrate of neutrophils throughout the dermis enables differentiation from pyoderma gangrenosum. The absence of vasculitic changes distant from ulceration helps to exclude a necrotizing vasculitis. Histopathologic Features Lipodermatosclerosis at a fully developed stage is typified by extensive fibrosis and sclerosis throughout the dermis and the subcutaneous tissue. In the subcutis, the fibrosis appears first as thickening ofthe septa but, with time, the lobules will be largely replaced by fibrosis and sclerosis so that the first impression in a biopsy might be that of a "thickened dermis, no subcutis sampled. Vessel proliferations may also be encountered around the superficial and/or deep plexus of the dermis. Not uncommonly, the epidermis is acanthotic with signs oflichen simplex or with a spongiotic dermatitis in the form of a superimposed Morphea profunda and eosinophilic fasditis (shulman syndrome) Morphea profu. Eosinophilic fasciitis has been associated with drugs, vigorous exercise, and malignancy, most often with hematopoietic malignancies. The term "fasciitis-panniculitis syndrome" has been proposed to designate a ·sclerosing reaction pattern" that occurs in a number of conditions,31 including morphea profu. Occasionally morphea may manifest itself as a linear processes (en coup de sabre) often found on the head. The inflammatory infiltrates generally are most prominent in the early stages and have a perivascular and interstitial and septa! The lymphoplasma cellular infiltrates also vary in density from sparse infiltrates to large nodules with germinal centers. Eosinophils in the infiltrate are not required for the diagnosis of eosinophilic fasciitis since the name refers to associated blood eosinophilia, not tissue eosinophilia. Variable mucin deposition and signs of vascular damage may be encountered in eosinophilic fasciitis. During its course, morphea may progressively involve the entire panniculus (including blood vessels, nerves, and other adnexae except arrector pill muscles) and occasionally the fascia. Necrobiosis lipoidica also shows extensive sclerosis but is associated with granulomatous inflammation and zones of necrosis. Lupus panniculitis may show some similarities to an inflammatory stage of morphea, but the pattern is that of a lobular panniculitis with less septa! Serological confirmation is also helpful because in chronic manifestations of borreliosis usually IgG antibodies against borrelia are found in very high titers. Lymphoplasmocytic infiltrates are found perivascular and at the periphery of fat lobules. Posttrradlation pseudoscleroderrnatous pannlculltts Postirradiation pseudosclerodermatous panniculitis is a rare complication ofradiation therapy. Cfinical Features Patients present with erythematous indurated plaques and/or subcutaneous nodules in an area of previously irradiated tissue. Nephrogenic systemic fibrosis Nephrogenic systemic fibrosis was first described by Cowper and colleagues in 2000. Later it was understood that the fibrotic process in these patients is not restricted to the skin but also affects connective tissues in other organs. Since 2007 gadolinium-based magnetic resonance imaging contrast agents have been avoided in patients with kidney insufficiency and in pediatric patients. However, new gadolinium-based contrast agents with less risk for nephrogenic systemic fibrosis have now been developed (gadoteridol, gadobenate dimeglumine). Patients who have decreased kidney function or chronic kidney disease are at higher risk for an adverse reaction to gadolinium-based contrast media. Macrocyclic contrast agents are considered safer than linear contrast agents for patients at risk for developing nephrogenic systemic fibrosis. To decrease the risk for nephrogenic systemic fibrosis, doses of gadolinium have to be adjusted to the glomerular filtration rate in patients who have decreased kidney function. In some patients, resolution is observed in the absence of any therapy; in others, improvement of skin lesions may be achieved with plasmapheresis. It has been shown that improvement of renal function through either transplantation or resolution of acute kidney injury with medical management is significantly associated with improvement of nephrogenic systemic fibrosis. Necrobiosis lipoidica is a rare chronic granulomatous disease that is frequently seen in patients with diabetes. Patients are predominantly female and present with indurated plaques on both shins that may eventually lead to atrophy and/or ulceration. Thus underlying pathogenic processes leading to microalbuminuria and retinopathy must differ. Randomized controlled trials to evaluate the many treatment methods are lacking thus far. Lesions develop weeks to months or even years after administration of gadolinium-based magnetic resonance imaging contrast agents. Histopathologic Features the subcutaneous septa are thickened and the lobules are constricted and may show signs of fat necrosis. Infiltrate of lymphocytes and plasma cells around venules are sparse, and eosinophils are rare. Differential Diagnosis Histopathologically, the pattern of changes is reminiscent of morphea, but infiltrates of lymphocytes are sparse and the interstitial cells increased in frequency are fibrocytes rather than lymphocytes.
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Other morphological features are very variable blood pressure variation during the day buy discount plendil 2.5 mg online, depending on the precise nature of the condition [1] blood pressure chart low to high order genuine plendil line. Reticulocytosis is usual but will be lacking if there is coexisting parvovirus B19 infec tion or, in rare patients, if there is marked bone mar row erythrophagocytosis [16]. The degree of hyperplasia reflects the extent to which the red cell life span is shortened. This has led, for example, to misdiagnosis as congenital dyserythropoietic anaemia in a case of pyruvate kinase deficiency [17]. A child with homozygosity for SouthEast Asian ovalocytosis, rescued by intra uterine transfusion, was found to have dyserythro poiesis with bi and multinuclearity, karyorrhexis, abnormal mitoses and enlarged late erythroblasts [18]. Dyserythropoiesis is often very striking when severe haemolytic anaemia occurs in a neonate. Macronormoblastic erythropoiesis should be distin guished from mildly megaloblastic erythropoiesis which may occur in the haemolytic anaemias when there is complicating folic acid deficiency. When haemolysis is extravascular, bone marrow mac rophages are increased and contain cellular debris. Iron stores are commonly increased, except when there is severe intravascular haemolysis with consequent loss of iron from the body. The number of erythroid islands is increased and the central macrophage is large and prominent, often staining a brownishgreen colour with a Giemsa stain because of the presence of increased haemosiderin. Splenomegaly and expansion of the bone marrow cavity are common, as are jaundice (reflecting both ineffective erythropoiesis and shortened red cell life span) and gallstones. Both peripheral blood and bone marrow aspirate features are important in making the diagnosis. In all categories, the reticulocyte count is not elevated appropriately for the degree of anaemia. Dyserythropoiesis without anaemia has been described in a single patient with Ellisvan Creveld syndrome (a rare autosomal recessive disorder characterized by chondrodyspla sia, ectodermal dysplasia, polydactyly and congenital heart disease) [26]. A dyserythropoietic anaemia has been reported in occasional patients with meva lonate kinase deficiency [27]. Megaloblastic anaemia Megaloblastic anaemia is usually consequent on deficiency of vitamin B12 or folic acid. The presence of megaloblastic anaemia can usually be suspected from examination of the peripheral blood film and, if features are totally typical, bone marrow aspiration is often not done. The ready availability of rapid and generally accurate assays for vitamin B12 and folic acid has lessened the importance of bone marrow examination. However, if typical peripheral blood features of megaloblastic eryth ropoiesis are lacking or if atypical features are present, bone marrow aspiration should be per formed. Bone marrow aspiration may also be required when the blood film suggests megalo blastic anaemia but assays are normal. Further tests indicated in patients with megaloblastic anaemia are assays of serum vitamin B12 and red cell or serum folate followed, when appropriate, by tests for autoantibodies. If pernicious anaemia is suspected, tests for parietal cell and intrinsic factor antibodies are indicated; the former is more sensitive but less specific than the latter. If coeliac disease is suspected as a cause of malabsorption of folic acid or vitamin B12, tests indicated include those for relevant autoantibodies (antitissue transglutaminase and possibly antiendomysium antibodies), antigliadin antibodies and a small bowel biopsy. In young infants the possible causes of megalo blastic anaemia are rather different from the causes later in life. Peripheral blood In most cases there is a macrocytic anaemia, with oval macrocytes being particularly characteristic. Some degree of anisocytosis and poikil ocytosis is usual and, when anaemia is severe, there are striking morphological abnormalities including the presence of teardrop poikilocytes, fragments, basophilic stippling and occasional HowellJolly bodies and circulating megaloblasts. Hypersegmented neutrophils are usually present; they are highly suggestive of megaloblastic erythropoiesis although not pathognomonic. They persist for a week or more after commencement of vitamin B12 or folic acid therapy. There can also be increased numbers of macropolycytes (tetraploid neutrophils) but this feature is less strongly associated with megaloblas tic erythropoiesis. These are large cells with a chromatin pattern more primitive than is appropriate for the degree of mat uration of the cytoplasm. Late megaloblasts may be fully haemoglobinized and lack any cytoplasmic basophilia. Erythropoiesis is ineffective so that early erythroid cells are overrepresented in comparison with mature cells; macrophages are increased and con tain defective red cell precursors and cellular debris. An iron stain shows abnormally prominent siderotic granules and sometimes occasional ring sideroblasts. The mitotic count is increased and examination of cells in metaphase may show that chromosomes are unusually long. They are two to three times the size of a normal metamyelocyte and often have nuclei of unusual shapes. Myelocytes and promyelo cytes are also increased in size but this abnormality is less obvious and less distinctive than the abnor mality of metamyelocytes. When megaloblastic fea tures in erythroblasts are partly or largely masked by coexisting iron deficiency, the detection of giant metamyelocytes is diagnostically important. Megakaryocytes are hyperlobated and have more finely stippled chromatin than normal megakaryocytes. The later erythroid cells show asyn chrony of nuclear and cytoplasmic maturation with cells having immature nuclei but haemoglo binized cytoplasm. Granulocytic precursors are increased but may appear relatively inconspicuous in the presence of profound erythroid hyperplasia. The likelihood of these errors has probably increased in recent years as haema tologists have had less experience in interpreting bone marrows from patients with straightforward megaloblastic anaemia. However, confusion with pure erythroid leukaemia, in which the primitive cells present are all erythroid, can occur.
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Their presence appears to correlate with resistance to intensive chemotherapy [234] heart attack 720p movie plendil 5 mg order on line. Abnormal localization of immature precursors (see page 237) is sometimes present and there may be an absolute increase in blast cells blood pressure medication yellow pill generic plendil 2.5 mg without prescription. Cytogenetic and molecular genetic analysis Clonal cytogenetic abnormalities that may be found include +8, -7, del(7q) and abnormalities of 12p. Misidentification of immature monocytes as promonocytes can lead to a misdiagnosis of acute monocytic leukaemia. Problems and pitfalls A careful assessment of cytological features is essential to distinguish atypical immature mono cytes from promonocytes. The disorder appears to arise in a multipotent myeloid stem cell or possibly, since occasional lymphoblastic transfor mations have been observed, in a pluripotent hae mopoietic stem cell. Some cases show marked clump ing of nuclear chromatin in neutrophils and pre cursors. However, the marrow is much more disorderly with disruption of normal architecture. The monocytes are recognized by their irregular nuclei with chromatin being less condensed than in neutrophil nuclei and moderate amounts of cytoplasm, which stains pink with H&E. Some cases are cytogenetically normal while others show clonal cytogenetic abnormalities such as trisomy 8 or del(20q). Bone marrow cytology the bone marrow shows increased cells of granulo cyte and sometimes monocyte lineages. Consideration of the clinical features and, if necessary, reexamination of blood and bone marrow after a period of followup, permits the correct diagnosis to be made. Three quarters of affected children are under the age of 3 years, with the incidence in boys being twice that in girls. Clinical features often include anaemia, hepatomegaly, splenomegaly, lymphadenopathy, tonsillar enlargement and rash. Erythropoiesis may show reversion to features of fetal erythropoiesis (high haemoglobin F and red cell carbonic anhydrase and low haemoglobin A2). There is often hypergammaglobulinaemia and there is an increased prevalence of autoantibodies. Many cases are cytogenetically normal at presentation but develop clonal abnormalities during the course of the disease. Overall, 4067% have been reported to be cytogenetically normal, 2533% have been found to have monosomy 7, and 1025% to have had other chromosomal abnormalities including trisomy 8 and other abnor malities of chromosome 7 [241]. Investigation of these features plus cytoge netic and molecular genetic analysis and appropriate viral studies is useful when there is diagnostic difficulty. Bone marrow cytology the bone marrow aspirate shows ring sideroblasts and may show other dysplastic features. Megakaryocytes can be large with hyperlobated nuclei and reticulin deposition can be mildly increased. One patient has been reported with ins(3;3)(q26;q21q26) [247] but this case should probably not be assigned to this category. In the 2016 revision it is a definitive entity, redesignated myelo dysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis [246]. Survival is longer than that of myelodysplastic syndrome with ring sidero blasts and single lineage dysplasia but worse than that of essential thrombocythaemia [246]. Peripheral blood There is a normocytic or macrocytic anaemia and often a dimorphic blood film. The therapeutic implica tions of these diagnoses illustrate the importance of moving, when possible, to a molecular classification of haemopoietic neoplasms. Acute lymphoblastic transformation (T or B lineage) can occur in these cases also. Peripheral blood There is usually hypereosinophilia but this is not invariable [259]. Neutrophils are sometimes increased and there may be anaemia and thrombocytopenia. Bone marrow histology Bone marrow trephine biopsy sections show an increase of eosinophils and their precursors. They usually have splenomegaly and may have cardiac and other tissue damage as a result of release of eosinophil granule contents. Cytogenetic and molecular genetic analysis Cytogenetic analysis is usually normal. Problems and pitfalls the differential diagnosis includes other causes of hypereosinophilia. If this molecular lesion is found, the diagnosis is not idiopathic hypereosinophilic syndrome. Despite the increase in mast cells in both conditions, this is a quite different disease from systemic mastocytosis with a different molecular lesion and different therapeutic and prognostic implications. This condition is about twice as common in men as in woman with peak incidence being in early middle age. Peripheral blood There is usually eosinophilia and sometimes mono cytosis or neutrophilia. Cytogenetic and molecular genetic analysis In addition to the most often observed transloca tion, t(5;12)(q32;p13. Problems and pitfalls this condition should not be confused with systemic mastocytosis. Peripheral blood Eosinophilia and neutrophilia are usual and some patients have monocytosis.
Syndromes
- Dry mouth
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- HSV-1 usually affects the mouth and lips and causes cold sores or fever blisters. However, it can spread from the mouth to the genitals during oral sex. For more information on HSV-1, see: Herpes labialis
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Artefacts can be induced by a previous aspiration or trephine biopsy at the same site heart attack 70 blockage plendil 10 mg lowest price. A bone marrow aspiration performed immediately before a tre phine biopsy usually causes haemorrhage fetal arrhythmia 33 weeks purchase online plendil, disrup tion of the tissue and loss of haemopoietic cells. This artefact can be avoided if the aspiration and trephine biopsy nee dles are introduced several millimetres apart and angled somewhat differently. A biopsy performed some time previously may lead to the pathological specimen showing fat necrosis, with focal collections of foamy mac rophages, or granulation tissue. A biopsy performed inadvertently at the site of a healing fracture pro duces a similar histological picture. There is initially granulation tissue, increased reticulin deposition and new bone formation; this can be confused with myelofibrosis [98]. Subsequently, granulation this sue is usually replaced by adipose tissue in which islands of haemopoietic cells develop. Scars should not be confused with fibrosis resulting from other patho logical processes. Report of an Intercollegiate Working Party chaired by the Royal College of Anaesthetists. Stellon A, Davies A and Williams R (1985) Avulsion of the anterior superior iliac spine complicating bone biopsy. Kansara G, Hussain M and Dimauro J (1989) A case of plasmacytoma in muscle as a complication of needle track seeding after percutaneous bone marrow biopsy. Fowler N, Asatiani E and Cheson B (2008) Needle track seeding after bone marrow biopsy in non Hodgkin lymphoma. Fox T, Jager R and Kirit A (2018) Cerebrospinal fluid leak after bone marrow biopsy. Kerndrup G, Pallesen G, Melsen F and Mosekilde L (1980) Histomorphometric determination of bone marrow cellularity in iliac crest biopsies. Meunier P, Aaron J, Edouard C and Vignon G (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. Ramsay A, Pomplun S and Wilkins B (2017) Tissue pathways for lymph node, spleen and bone marrow trephine biopsy specimens. This article will deal predom inantly with special techniques that are applicable to bone marrow aspirates and trephine biopsy sections but reference will be made to the periph eral blood where this is the more appropriate tissue for study. Other diagnostic procedures that may be of use in individual cases include cytochemistry, immu nophenotyping (by immunocytochemistry or, more usually, flow cytometry), cytogenetic and molecular genetic analysis, ultrastructural exami nation, culture for microorganisms and culture for assessment of haemopoietic progenitor cells. In most countries, histological sections cut from bone marrow trephine biopsy specimens are stained routinely with H&E. Giemsa staining permits the easy identification of mast cells, facilitates recognition of plasma cells and helps in making a distinction between early erythroid cells and myeloblasts. If a Giemsa stain is not performed routinely then it is important that it is used whenever necessary for these indications. Other techniques that may be applied to trephine biopsy sections include a wider range of cytochemical stains, immunohistochemistry, cyto genetic and molecular genetic analysis (parti cularly in situ hybridization) and ultrastructural examination. Consequently it allows assessment of both the amount of iron in macrophage stores and the availability of iron to developing erythroblasts. Occasionally in patients who have received parenteral iron, there is granular positivity in endothelial cells [2]. Assessment of storage iron requires that an ade quate number of fragments are obtained. A mini mum of seven fragments in one or more bone marrow films need to be examined in order to state with reasonably reliability that bone marrow iron is absent [3]. A bone marrow film or squash preparation will contain both intracellular and extra cellular iron, the latter being derived from crushed Bone Marrow Pathology, Fifth Edition. It is usual to base assessment of iron stores mainly on intracellular iron since iron stains are prone to artefactual deposits and it can be diffi cult to distinguish between extracellular iron and artefact. Iron stores may be assessed as normal, decreased or increased or may be graded as 1+ to 6+ as shown in Table 2. In routine practice, grading as absent, scanty, reduced, normal or increased is also a practical approach. In haematologically nor mal subjects with adequate iron stores, 2050% of bone marrow erythroblasts are sideroblasts [810]. Examination of an iron stain allows detection not only of an increased or decreased proportion of sideroblasts but also of abnormal sideroblasts. The latter include those in which siderotic granules are merely increased in size and number and those in which granules are also distributed abnor mally within the cytoplasm, being sited in a ring around the nucleus rather than randomly (ring sideroblasts). In certain pathological conditions, plasma cells contain haemosiderin inclusions, which are irreg ular in shape and relatively large. Haemosiderin inclusions in plasma cells are observed mainly in iron overload (for example in haemochromatosis and transfusional siderosis) and in chronic alcoholism [11]. Problems and pitfalls Since iron is distributed irregularly within bone marrow macrophages it is necessary to assess a minimum of seven fragments before concluding that storage iron is absent or reduced. Careful examination will show that it is not related to cells and is often in another plane of focus. In acute leukaemia there may be numerous blast cells in the peripheral blood and it is then useful to perform cytochemical stains on blood and bone marrow in parallel. The techniques recommended for diagnosis and classification of acute leukaemia are either myeloperoxidase or Sudan black B staining, to identify cells showing granulocytic differentiation, plus a nonspecific esterase or combined esterase stain, to identify cells showing monocytic differentiation. Other cytochemical stains that are occasionally used include toluidine blue to demonstrate the metachromatic granules in basophils and mast cells and staining of cells of mast cell lineage for aminocaproate; however such stains have largely been replaced by immunohistochemical stains. Cytochemistry now has little place in the investigation of lymphoproliferative disorders.
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It occurs more commonly in children adopted from orphanages with suboptimal facility cleanliness blood pressure medication dizzy order plendil 10 mg mastercard. There is minimal papillary dermal edema and a sparse mixed-cell perivascular infiltration blood pressure of 150 100 plendil 5 mg purchase on-line. Differential Diagnosis See "IgA Pemphigus" and "Impetigo and Bullous Impetigo" above. Transient neonatal pustular melanosis Clinical Features Flaccid vesicopustules on the trunk and diaper area are present at birth. The pathogenesis is unknown, but this transient dermatosis occurs in healthy full-term infants. Their appearance in a background of normal skin is characteristic and differs from the diffuse macular papular skin rash. Histopathologic Features In macular lesions, a sparse perivascular infiltrate is associated with mild papillary dermal edema. The papules reveal numerous eosinophils and some neutrophils in the outer root sheath of hair follicles, giving rise to eosinophilic pustules overlying follicular orifice (see Table 7-13). Intraepidermal subcomeal pustules consisting predominantly of eosinophils are also present1°" Differential Diagnosis See "Neonatal Pustular Melanosis" above. One also might consider eosinophilic pustular folliculitis/pustulosis in the differential diagnosis, although folliculocentricity is not a constant feature. Due to the subcomeal nature of the pustule and supervening acantholysis, the differential diagnosis must also encompass IgA pemphigus. The biopsy shows intraepidermal pustulation whereby the pustule had a mixed composition comprising neutrophils and eosinophils and was associated with keratinocyte injury. Histopathologic Feahlres Vesicopustules in the intracomeal or subcomeal zones contain neuuophils with an admixture of eosinophils. The papillary dermis is edematous with an infiltrate of neutrophils and eosinophils around superficial veuels. Some have suggested that erythema toxicum neonatorum and neonatal pustular melanosis are related disorders. Erythema toxlcum neonatorum ainical Features Erythema to:ricum neonatorum is characterized by an extensive macular and papular erythematous skin rash whereby pustules can occur but are rather uncommon. When they do develop they are superimposed on abnormal skin that includes macules, papules, or wheals distributed on the face, torso, and proximal extremities (Table 7-13). The pustules arise within the first 2 days of life, being occasionally present at birth. The relennce of the IgG subclasa of autoantibodies for blister induction in autoimmune bullow ·kin disease. Drug-induc:ed pemphlgus: autoantibodies directed against the pemphlgw antigen complexes are present in penicillamine and captopril-induc:ed pemphigu1. The Ulle of C3d and C4d as a diagnostic adjunct in the evaluation of inflammatory skin dis cue. Paraneoplastlc pemphigu& and autcimmwte blistering diseases asaociated with neoplaam: characterillia. The prevalence of antibodies against desmoglein 1 in endemic pemphigus foliaceus in Brazil. Cytokine and chemokines alterations in the endemic form of pemphigus foliaceus (fogo selvagem). Clinical and immunological profiles in 17 Japanese patients with drug-induced pemphigus studied at Kurume University. Intraepidermal neutrophilic dermatosis type of IgA pemphigus with circulating linear IgA disease antibodies associated with ulcerative colitis. Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis. Clinical, histopathological and immunological distinction in two cases of IgA pemphigus. Epidermal polymeric immunoglobulin receptors: leads from intraepidermal neutrophilic IgA dermatosis-type IgA pemphigus. The clinical and histopathological spectrum of IgA-pemphigus-report of two cases. A typical case of paraneoplastic pemphigus without detection of malignancy: effectiveness of plasma exchange. Paraneoplastic pemphigus presenting as a lichen planus pemphigoides-like eruption. Sera from patients with toxic epidermal necrolysis contain autoantibodies to periplakin. Adult case of staphylococcal scalded skin syndrome differentiated from toxic epidermal necrolysis with the aid of dermoscopy. The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study. Localization of the gene whose mutations underlie Hailey-Hailey disease to chromosome 3q. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma. Two cases of amoxycillin-induced follicular acute localised exanthematous pustulosis. Epidemiology and predisposing factors for erythema toxicum neonatorum and transient neonatal pustular: a multicenter study. Genetic mutations in the Kl and Kl O genes of patients with epidermolytic hyperkeratosis. Multiple epidermolytic acanthomas mimicking condyloma: a retrospective study of 8 cases. Epidermolytic hyperkeratosis in the lower female genital tract: an uncommon simulant of mucocutaneous papillomavirus infection-a report of two cases.
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