Michael A. Bohrn, MD, FAAEM, FACEP

• Associate Residency Program Director, Clinical Assistant Professor,
• Department of Emergency Medicine, York Hospital, York, PA, USA

The lower border of each visceral pleura lies two ribs higher than the parietal pleural reflection symptoms ear infection purchase lithium 300 mg mastercard. It covers the base of the lung and gets continuous with mediastinal pleura medially and costal pleura laterally symptoms quit drinking buy lithium 150 mg. Features of Parietal Pleura the parietal pleura is thicker than the pulmonary pleura treatment zone guiseley buy cheapest lithium, and is subdivided into the following four parts treatment definition math cheap lithium 150 mg fast delivery. It is reflected over the root of the lung and becomes continuous with the pulmonary pleura around the hilum symptoms zinc deficiency adults order lithium with amex. The cervical pleura extends into the neck medications kidney patients should avoid cheap 150 mg lithium mastercard, nearly 5 cm above the first costal cartilage and 2. Cervical pleura is related anteriorly to the the cervical pleura is represented by a curved line forming a dome over the medial one-third of the clavicle with a height of about 2. The anterior margin, or the costomediastinal line of pleural reflection is as follows: On the right side, it extends from the sternoclavicular joint downwards and medially to the midpoint of the sternal angle. From here, it continues vertically downwards to the midpoint of the xiphisternal joint crosses to right of xiphicostal angle. It then arches outwards and descends along the sternal margin up to the sixth costal cartilage. The inferior margin, or the costodiaphragmatic line of pleural reflection passes laterally from the lower limit of its anterior margin, so that it crosses the eighth rib in the midclavicular line, the tenth rib in the midaxillary line, and the twelfth rib at the lateral border of the sacrospinalis muscle. Thus the parietal pleurae descend below the costal margin at three places, at the right xiphicostal angle, and at the right and left costovertebral angles, below the twelfth rib behind the upper poles of the kidneys. Pulmonary Ligament the parietal pleura surrounding the root of the lung extends downwards beyond the root as a fold called the pulmonary ligament. Actually, it provides a dead space into which the pulmonary veins can expand during increased venous return as in exercise. This recess is filled up by the anterior margin of the lungs even during quiet breathing. The costodiaphragmatic/costovertebral recess lies inferiorly between the costal and diaphragmatic pleurae. The costal and peripheral parts of the diaphragmatic pleurae are supplied by the intercostal nerves, and the mediastinal pleura and central part of the diaphragmatic pleurae are supplied by the phrenic nerves (C4). The pulmonary pleura develops from the splanchnopleuric layer of the lateral plate mesoderm, and is supplied by autonomic nerves. The sympathetic nerves are derived from second to fifth sympathetic ganglia while parasympathetic nerves are drawn from the vagus nerve. The parasympathetic system narrows the bronchial tree and is also secretory to the glands. Its blood supply and lymphatic drainage are, therefore, the same as that of the body wall. It is thus supplied by intercostal, internal thoracic and musculophrenic arteries. The lymphatics drain into the intercostal, internal mammary, posterior mediastinal and diaphragmatic nodes. The pulmonary pleura, like the lung, is supplied by the bronchial arteries while the veins drain into bronchial veins. The needle is passed through the lower part of the space to avoid injury to the principal neurovascular bundle, i. It may be dry, but often it is accompanied by collection of fluid in the pleural cavity. Dry pleurisy is more painful because during inspiration both layers come in contact and there is friction. Hence irritation of these regions cause referred pain along intercostal nerves to throacic or abdominal wall. Mediastinal and central parts of diaphragmatic pleurae are innervated by phrenic nerve (C4). The deoxygenated blood gets oxygenated and sent via pulmonary veins to the left atrium of heart. These are right and left cervical pleurae above the 1st rib and the clavicle; right and left costovertebral angles and only right xiphicostal angle. On the third day, he developed severe cough, difficulty in breathing and high temperature, with pain in his right side of chest, right shoulder and around umbilicus. Pleura consists of two layers- visceral and parietal; the former is insensitive to pain and the latter is sensitive to pain. The costal part of parietal pleura is supplied by intercostal nerves and the mediastinal and central parts of diaphragmatic pleurae are supplied by phrenic nerve (C4). Due to infection in mediastinal and central part of diaphragmatic pleura, the pain is referred to tip of the right shoulder as this area is supplied by supraclavicular nerves with the same root value as phrenic nerve (C4). So the pain of lower part of costal pleura gets referred to skin of abdomen, in the periumbilical area. Anatomical and surgical considerations of the phrenic and accessory phrenic nerves. Vascular endothelial growth factor as a consequentional marker in chronic obstructive pulmonary disease. The two lungs hold the heart tight between them, providing it the protection, it rightly deserves. Gradually, they become mottled black because of the deposition of inhaled carbon particles. The right lung weighs about 700 g; it is about 50 to 100 g heavier than the left lung. On the mediastinal part of the medial surface of right lung identify two bronchi-the eparterial and hyparterial bronchi, with bronchial vessels and posterior pulmonary plexus, the pulmonary artery between the two bronchi on an anterior plane. The upper pulmonary vein is situated still on an anterior plane while the lower pulmonary vein is identified below the bronchi. The impressions on the right lung in front of root of lung are of superior vena cava, inferior vena cava, and right ventricle. The impressions behind the root of lung are those of vena azygos and oesophagus (Table 16. Hilum of the left lung shows the single bronchus situated posteriorly, with bronchial vessels and posterior pulmonary 264 plexus. Anterior to the bronchus is the upper pulmonary vein, while the lower vein lies below the bronchus. The mediastinal surface of left lung has the impression of left ventricle, ascending aorta. On the right side, it is vertical and corresponds to the anterior or costomediastinal line of pleural reflection. The anterior border of the left lung shows a wide cardiac notch below the level of the fourth costal cartilage. The heart and pericardium are not covered by the lung in the region of this notch. It extends from the level of the seventh cervical spine to the tenth thoracic spine. The medial surface is divided into a posterior or vertebral part, and an anterior or mediastinal part. The mediastinal part is related to the mediastinal septum, and shows a cardiac impression, the hilum and a number of other impressions which differ on the two sides. Various relations of the mediastinal surfaces of the two lungs are listed in Table 16. The right lung is divided into three lobes (upper, middle and lower) by two fissures (oblique and horizontal). The oblique fissure cuts into the whole thickness of the lung, except at the hilum. It passes obliquely downwards and forwards, crossing the posterior border about 6 cm below the apex and the inferior border about 5 cm from the median plane. Due to the oblique plane of the fissure, the lower lobe is more posterior and the upper and middle lobes more anterior. In the right lung, the horizontal fissure passes from the anterior border up to the oblique fissure and separates a wedge-shaped middle lobe from the upper lobe. The fissure runs horizontally at the level of the fourth costal cartilage and meets the oblique fissure in the midaxillary line. The tongue-shaped projection of the left lung below the cardiac notch is called the lingula. The lungs expand maximally in the inferior direction because movements of the thoracic wall and diaphragm are maximal towards the base of the lung. The presence of the oblique fissure of each lung allows a more uniform expansion of the whole lung. Surface Marking of the Lung Surface marking of lung is same as that of visceral pleura described in Chapter 15. Left ventricle, left auricle, infundibulum and adjoining part of the right ventricle 2. Anterior pulmonary plexus, lymph nodes and lymph vessels in the anterior and inferior parts. Single bronchus with bronchial vessels and posterior pulmonary plexus along its posterior wall. A point on the anterior border of the right lung at the level of the fourth costal cartilage. Posterior pulmonary plexus 2 On left side: Descending thoracic aorta Superior 1 On right side: Terminal part of azygos vein 2 On left side: Arch of the aorta. Differences between the Right and Left Lungs Root of the Lung Root of the lung is a short, broad pedicle which connects the medial surface of the lung to the mediastinum. It is formed by structures which either enter or come out of the lung at the hilum (Latin depression). The roots of the lungs lie opposite the bodies of the fifth, sixth and seventh thoracic vertebrae. It has only one fissure and 2 lobes 1 On the right side, there is one bronchial artery which arises from the third right posterior intercostal artery. Deoxygenated blood is brought to the lungs by the two pulmonary arteries and oxygenated blood is returned to the heart by the four pulmonary veins. The greater part of the venous blood from the lungs is drained by the pulmonary veins. The vessels pass round the borders of the lung and margins of the fissures to reach the hilum. The superficial vessels have numerous valves and the deep vessels have only a few valves or no valves at all. Though there is no free anastomosis between the superficial and deep vessels, some connections exist which can open up, so that lymph can flow from the deep to the superficial lymphatics when the deep vessels are obstructed in disease of the lungs or of the lymph nodes. Nerve Supply 2 Sympathetic nerves are derived from second to fifth sympathetic ganglia. That is how sympathomimetic drugs, like adrenaline, cause bronchodilatation and relieve symptoms of bronchial asthma. Sensory fibres are responsible for the stretch reflex of the lungs, and for the cough reflex. The trachea divides at the level of the lower border of the fourth thoracic vertebra into two primary principal bronchi, one for each lung. Inhaled particles or foreign bodies, therefore, tend to pass more frequently to the right lung, with the result that infections are more common on the right side than on the left. Each principal bronchus enters the lung through the hilum, and divides into secondary lobar bronchi, one for each lobe of the lungs. Thus there are three lobar bronchi on the right side, and only two on the left side. Each lobar bronchus divides into tertiary or segmental bronchi, one for each bronchopulmonary segment; which are 10 on the right side and 10 on the left side. The segmental bronchi divide repeatedly to form very small branches called terminal bronchioles. Each respiratory bronchiole aerates a small part of the lung known as a pulmonary unit. Remove the pulmonary tissue and follow the main bronchus till it is seen to divide into two lobar bronchi. Remove the pulmonary tissue and follow the main bronchus till it is seen to divide into three lobar bronchi. Apical Posterior Anterior Lateral Medial Superior Medial basal Anterior basal Lateral basal Posterior basal B. Lower Bronchopulmonary segments are well-defined anatomical segments aerated by tertiary/segmental bronchus. These are pyramidal in shape with apex directed towards hilum and base directed towards periphery having their own arterial supply; but venous drainage is shared by adjacent bronchopulmonary segment. Superior lingular Inferior lingular Superior Medial basal Anterior basal Lateral basal Posterior basal 2 Section 1 these are well-defined anatomic, functional and surgical sectors of the lung. Relation to Pulmonary Artery the branches of the pulmonary artery accompany the bronchi. Relation to Pulmonary Vein the pulmonary veins do not accompany the bronchi or pulmonary arteries. Thus each segment has more than one vein and each vein drains more than one segment. It should be noted that the bronchopulmonary segment is not a bronchovascular segment because it does not have its own vein.

However medicine 54 543 discount 150mg lithium overnight delivery, careful examination should disclose the lack of significant atypia and the presence of other features typical of hidradenoma treatment 5th metatarsal stress fracture order 300 mg lithium with visa, including ductal structures medicine used to treat bv purchase lithium discount, cystic spaces symptoms jaundice purchase lithium 150mg without prescription, variable degrees ofclear cell change treatment 21 hydroxylase deficiency lithium 150mg with visa, and a hyalinized stroma treatment low blood pressure cheap lithium online master card. Hidradenoma may show slight cytologic atypia and mitotic figures, raising the possibility of malignancy. In general, benign tumors are characterized by a well-circumscribed appearance without evidence ofinfiltration of the adjacent tissue, no nuclear atypia. It is one of several neoplasms that may be associated with news sebaceus ofJadassohn, but it most often occurs as a sporadic tumor. Characteristic: tubular ducts lined by low columnar epithelia with apoc:rine-type decapitation secretion ("snouts"). The neoplastic cells have compact oval nuclei and arnphophilic to eosinophilic cytoplasms, and overt mucinous metaplasia may sometimes be seen. Cytologic at:ypia is variable but is generally unremarkable; however, rumors that have been subjected to mechanical trawna or other insults may show nuclear pleomorphism. At the interface between the epidermis and the neoplasm, keratinocytes give way to aggregates of cuboidal. There are slender double-layered tubular apocrine ducts emanating from the epidermis and invading the upper dermis, where they may form small cystic spaces. There is a predominance of tubular apocrine elements and solid slender epithelial strands and pseudopapillae. Careful attention to cytologic, architectural, and (if necessary) immunohistologic features of the tumor in question should be sufficient to make this diagnostic separation. This is the ability for a primordial "stem cell" population to pursue divergent differentiation at a morphologic level into dissimilar target tissues. Hence, one is faced with a structural phenotype in which slightly branching tubules and clusters of epithelial cells with variable cytologic appearances (eg, eccrine, apocrine, sebaceous, pilar, mucinous, simple glandular, "hyaline" or plasmacytoid, or squamoid) are admixed intimately but randomly with zones of matrical tissue that look like cartilage, bone, muscle, myxoid mesenchyme, and fat, sometimes all in the same mass! Thus, the name "mixed tumor" is particularly apropos because not only are epithelial and mesenchymal tissues interspersed but the subtypes of those tissues also are heterogeneous, and their relative proportions are greatly variable. Nonetheless, the differential diagnosis, on occasion, may include cutaneous cartilaginous tumors such as chondroma, lipoma variants, 106 and other appendageal tumors, particularly hidradenoma. On occasion, some mixed tumors may show a limited epithelial component consisting of single epithelial cells and minimal tubular structures. It may be necessary to resort to immunohistochemistry to distinguish these 2 processes. In addition, whereas mixed tumors are more common in the head and neck area, cartilaginous tumors are more commonly localized to the distal extremities and frequently show prominent calcification. As previously discussed, a prominent stromal component is characteristic of mixed tumor versus the predominance of a lobular epithelial proliferation in hidradenoma. Other mixed-lineage adnexal adenomas Those who are experienced in examining appendageal tumors of the skin are accustomed to the fact that one regularly encounters lesions that are undoubtedly benign but that show more than one route of epithelial adnexal differentiation and are therefore difficult to classify. In that vein, admixtures of eccrine and apocrine, sudoriferous and pilar, pilar and sebaceous, or sweat glandular and sebaceous tissues may be observed in those neoplasms. The stromal component is prototypically chondroid as seen here but also may be to varying degree myxoid or fibrotic. The plasmacytoid cytology of these cells represents prototypical myoepithelial differentiation: these cells are myoepithelial. The categorization ofcarcinomas of the sweat glands obviously represents a microcosm of the nosology of cutaneous adnexal neoplasms in general. Because differential diagnostic considerations vary considerably in reference to various specific malignant sweat gland tumors, and, selectively, biologic and prognostic characteristics as well, a relatively detailed nomenclatural scheme for such neoplasms is more appropriate. In general, the best model for understanding the range of microscopic patterns expressed by cutaneous sweat gland malignancies is the spectrum of carcinoma morphotypes seen in the female breast m this similarity is not difficult to understand theoretically because it is widely acknowledged that the mammary glands represent large and somewhat specialized versions of the sudoriferous apparatus. One might expect that whereas some malignant adnexal tumors will have clinicopathologic characteristics that are sufficiently singular as to ensure their primary nature, others are. In general, these tumors tend to present in older individuals, most frequently in the seventh decade oflife. Hlstopathologlc Features Porocarcinomas are notable for the high frequency of local recurrence. The points of histologic dissimilarity between the benign and malignant lesions in this category include the presence in porocarcinomas ofinfiltrative growth (with desmoplastic stromal response); spontaneous tumor neaosis; obvious global qtologic anaplasia, with high nucleocytoplasmic ratios and nucl. Not all those features need be present to assign a diagnosis of malignancy; in fact, infiltrative growth is sufficient in this regard. Akalin and colleagues1:u have shown that both poroma and porocarcinoma may demonstrate p53 protein accwnulation immunohistologically; thus, that determinant is not useful in a distinction between the 2 tumor types. As expected, invasive porocarcinoma has both aaosyringium-like and dermal components, by definition. Lobular aggregates of atypical cuboidal tumor cells extend from epidermis into dermis. Scant solitary poroid car<:inomatous tumor nests within the epidennis are associated with dermal invasion by tumor aggregates with conspicuous cytological atypia. The last of these considerations is particularly important in cases of porocarcinoma in which the neoplastic cells divergently synthesize melanin (often causing clinicians to make a diagnosis of melanoma). Isolated cases with intraepidermal growth have been documented in reference to metastatic carcinomas in the skin, but this eventuality is extremely uncommon. In any event, recent publications have suggested that immune reactivity for keratins 5 and 6, p63 protein, or podoplanin (02-40) might be useful in the differential diagnosis of adnexal carcinoma versus metastatic carcinoma in the skin. As such, it shows the clonal, micronodular growth of atypical polygonal cells within the surface epithelium, yielding nests of tumor cells that are sharply marginated from adjacent kera1inocytes. Deeper forms of the tumor must be distinguished from invasive squamous cell carcinoma and hidradenocarcinoma. In general, poroearcinoma is characterized by foci of small cuboidal cell population as opposed to somewhat larger cells in conventional squamous cell carcinoma. Porocarcinoma typically shows preexisting areas of poroma and ductal or tubular structures. Porocarcinomas also have more frequent epidermal involvement as opposed to a more prevalent dermal location of hidradenoearcinoma. Careful clinicopathologic correlation may be needed to arrive at a final diagnosis. Hldradenocardnoma this category of carcinoma probably encompasses a group of tumors formerly named malignant acrospiroma. However, the presence af significant atypia and mitoses helps to distinguish this proliferation from architecturally similar examples af poroma. The cases previously reported have presented as nodules involving the head and neck area. Large lobular dermal tumor with superficial cystic space and comprised of irregular nests of basaloid tumor cells. Three morphologic variants have been described: tumors with a polypoid configuration, tumors characterizedby marked desmoplasia, and comedo variants showing central necrosis within lobular epithelial aggregates. Both basaloid and squamous foci may occur to varying extents in a given tumor and may predominate over clear cell alteration. It should be pointed out that cytologic features may vary from being well differentiated to anaplastic. Large lobular aggregates of tumor cells exhibit variable clear cell change and focal necrosis. Mucinous carcinoma is a distinctive tumor often presenting on the face and especially the eyelids as a skin-colored or oc. The vast majority of tumors develop in older individuals in the sixth and seventh deades of life. It is possible that these tumors may be more common in men and people of African ascendance. In general, mudnous carcinoma is prone to local recurrence but has a relatively low rate of regional lymph node metastasis. Histopathologic Features nuclei are generally oval with dispersed chromatin and small nucleoli; the cytoplasm is amphophilic or slightly eosinophilic and may be vacuolated. Mitotic figures are usually limited in number, and vascular or neural permeation is relatively uncommon. It is extremely similar, ifnot identical, histologicallyto mucinous (colloid) carcinoma of the breast or gastrointestinal tract. Nevertheless, on empirical grounds, this is not a frequent potentiality of mammary or digestive tract mucinous carcinomas and may be dismissed for that reason. In other words, colloid" carcinomas of the breasts, stomach, and intestines do not ever involve the skin unless the patient has a long-standing and disseminated tumor147; these neoplasms appear to lack the ability to selectively affect the dermis early in the course of disease. The distinction between those lesions is usually easily made by conventional microscopy in that the mesenchymoid zones of such:m. Dermal tumor beneath grenz zone showing diffusely dispersed tumor aggregates with tubular spaces and cribriform patterns. The overall growth pattern of both of those tumor types is infiltrative, and penneation of vascular adventitia and perineural spaces is potentially common to both ofthem as well. Qinical Features these tumors most commonly present in individuals of all ages as solitary nodules up to 2 cm in diameter localized to the fingers, toes, palms, and soles (Table 29-14). Digital amputation has been advocated for control of the primary neoplasm,184 but its use is now debated u conservative wide excision does not seem to alter the prognosis. Expression of p63 in the basal myoepithelial layer confirming that this neoplasm is in situ carcinoma. Scanning magnification discloses a tumor with stratification as evidenced by keratinous cysts in the superficial dermis giving place to infiltrating thin strands of tumor with depth. When incompletely excised, local recurrence rate is high, but true lymph node and distant metastasis is vanishingly rare, if it truly exists at all. Nonetheless, this variant differs from the latter tumor in emfbiting syringoid cell profiles Mlcrocystlc adnexal carcinoma Synonyms: Sc:lerosing sweat duct carcinoma, syringomatoid carcinoma. These cellular aggregates were occasionally punctuated by microcystic arrays containing pilar-type (trichilemmal) keratin. These tumors are generally perceived as slow-growing indolent tumors and may develop in individuals of any age but especially in young women. There may be morphological overlap with sclerotic squamous cell carcinoma in deeper parts of the tumor, albeit without the high degree of pleomorphism and hyperchromasia encountered in sec. As its name suggests, squamous carcinoma-like differentiation is seen in the upper part of the lesion and glandular foci with atypia are encountered more deeply, with the adenocarcinomatous areas having a potential for mucinous differentiation as well. Obviously, one may have difficulty in excluding ordinary squamous carcinoma if only a small biopsy specimen is obtained; however, if foci of epidermal connection are not seen because of sampling limitations, metastases may indeed be considered diagnostically. Cylindrocarcinomas and spiradenocarcinomas are carcinomas that evolve from "parent" cylindromas or spiradenomas. Because of such restrictive requirements, it is beyond reason that one would diagnostically consider metastasis to the skin from a visceral carcinoma in this context. Histopathologic Features Squamoid eccrine ductal carcinoma (adenosquamous carcinoma) Clinical Features A primary neoplasm of the skin has been described that occurs more commonly on the head and neck, most commonly in sun-damaged skin of elderly Caucasians with a male predominance. The malignant elements most often assume the character of an undifferentiated carcinoma, showing sheets or clusters of nondescript but highly anaplastic epithelioid, stellate, or fusiform tumor cells with marked anisonucleosis, nucleolar prominence, cellular pleomorphism, and brisk mitotic activity. It may have different patterns: adenocarcinoma (apocrine features), myoepithelial carcinoma. The latter pattern is characterized by a gradual transition from a carcinomatous element to sarcomatoid tissue with the appearance of pleomorphic or spindle cell sarcoma, or chondrosarcoma. Differential Diagnosis Any anaplastic tumor Apocrine carcinoma Apocrine carcinoma isa rare cutaneous neoplasm with unequivocal signs of apocrine secretion and is a diagnosis of exclusion. Consequently, other well-recognized tumors with apocrine differentiation such as syringocystadenocarcinoma papilliferum, mucinous carcinoma, cribriform carcinoma, and secretory carcinoma must be ruled out. Furthermore, apocrine carcinoma by definition is not associated with a preexisting. Under those circumstances, the only factor distinguishing such lesions from "ordinary" malignancies of the skin is the presence of the remnant adenoma. As another attestation to the possible kinship between spiradenoma and cylindroma, Carlsten and colleagues2u documented a malignant "hybrid" of both tum. It often results in regional lymph node metastases followed by visceral spread, in approximately 4096 of cases. To differentiate the 2 latter entities, immunohistochemistry may help, but any patient with a carcinoma of the skin showing an apocrine immunophenotype should have a thorough clinico-radiological examination of the breasts before a diagnosis of skin apocrine carcinoma is made. Clinical Features the tumor most commonly presents as a nodule or plaque, ulcerated on occasion, measuring 2 to 6 cm in greatest dimension, often in association with news sebaceu. Scanning magnification illustrates a tumor with glandular structures emanating from the epidermis and extending into the deep dermis. Tumor cells have finely granular eosinophilic cytoplasm and decapitation secretion. Phenotypic heterogeneity may be present, and squamous, basaloid, and sarcomatoid differentiation has been described in these lesions. Note contiguous outer layer of regular myoepithelia, heralding the in situ character of this apocrine carcinoma.

The term "chronic bite injury" should be reserved for lesions that result from chronic mucosa! Histologic changes of secondary chronic bite trauma may occur as an incidental finding in a localized fashion associated with another lesion symptoms renal failure quality lithium 300 mg, such as a fibroma treatment 100 blocked carotid artery discount lithium uk. Clinical Features Reticulation medicine expiration dates generic lithium 150 mg line, erythema symptoms 8 days before period cheap 300mg lithium free shipping, and/or ulcers of oral mucosa medications ocd discount 300 mg lithium mastercard, especially buccal mucosa medications in carry on luggage purchase lithium in india, lip mucosa, tongue, and gingiva Desquamative gingivitis Histopathologic Features Hyperkeratosis or hyperparakeratosis Squamatization of basal keratinocytes Colloid body formation Bandlike infiltrate of lymphocytes and histiocytes at interface of epithelium-connective tissue Chronic chewing habits are encountered in the teenage years and adulthood, and patients may be unaware of the habit. The most common locations are the buccal and lip mucosae and lateral tongue, all sites readily traumatized by teeth. The lesion is typically nontender and appears as grayish-white papules and plaques with irregular, shaggy, peeling surfaces, focal erosion, erythema, and sometimes ulcers. Supporting this latter theory is the finding that many of the patients with reported malignant transformation have a history of tobacco use. Among all lichenoid lesions, loss ofheterozygosity on chromosome arms 3p, 9p, and 17p is only found in those that also exhibit epithelial dysplasia. T lymphocytes migrate to the area, facilitated by adhesion molewles and cytokines (such as tumor necrosis factor alpha secreted by mast cells and endothelial cells. The epithelium is attenuated or eroded in the atrophic/ erosive type, often with small ulcers, and somewhat hyperplastic in the reticular/papular type. There is leukocyte e:xocytosis, an increased number of Langerhans cells, and variable numbers of colloid (Civatte) bodies. Melanophages and incontinent melanin may be present in the lamina propria, and plasma cells are prominent if there is overlying ulceration. In some cases, nodular peri- and paravascular lymphocytic aggregates may be a prominent feature, sometimes with lymphoid follicles within the lymphoid band. Some but not all of such cases are associated with hypersensitivity reactions to cinnamon-tlavored products. Lupus ery- Females are affected twice as often as males, and most are adult or middle-aged. Three clinical types have been identified, to wit: reticular/papular, erythematous/erosive/atrophic, and ulcerative/bullous types, usociated with increasing symptomology. The bullous type is rare because most bullae in the mouth rupture within a short time after their appearance. Many patients have combinations of these types, and generally, reticular white areas suggestive of Wickham striae are present at the periphery of erythematous and ulcerative lesions. The gingiva is painful and diffusely erythematous with areas of vesiculation, erosion, and desquamation, often covered by a white membrane that may represent a fibrin clot or the roof of a collapsed bulla. Para- or orthokeratin, sawtooth rete ridges, squamatization of basal cells, and a bandlike inflammatory cell infiltrate characterize oral lichen planus. The epithelial changes are less marked, and the lymphocytic infiltrate is sparse in oral chronic graftversus-host disease because of systemic immunosuppression. Lichenoid dysplasias represent epithelial dysplasias that incite a lichenoid tissue reaction. Direct immunofluorescence results in lichen planus pemphigoides revealing IgG, IgA, and C3 deposition along the basement membrane. Epithelial dysplasia may be seen in longstanding lesions where the keratin layer is usually more pronounced. Amyloid-like material may be seen in the lamina propria and within interstitium of minor salivary glands. Differential Diagnosis Nicotine (nicotinic) stomatitis this is a rare benign reactive lesion of the hard palate that is associated with excessive heat, typically generated by pipes or cigars. Clinical Features In its early stages, smokeless tobacco lesions represent direct topical injuries to the mucosa, producing the superficial layer of degenerated cells. Leukoedema does not exhibit chevron formation and does not have the distinct band of degenerated cells. Nicotine stomatitis is seen most often in older men because this population accounts for the majority of cigar and pipe smokers. The palatal mucosa appears white; red papules within these hyperkeratotic areas represent inflamed minor salivary gland duct orifices. Differential Diagnosis Benign migratory glossitis Synonyms: Geographic tongue, erythema areata migrans, erythema circinata, migratory stomatis. This evanescent inflammatory tongue condition occurs in between 1% and 2% of the population. The tongue presents with irregular maplike areas of Smokeless tobacco lesion Synonym: Smokeless tobacco keratosis. Smokeless tobacco lesions typically present as areas ofpoorly circumscribed gray-white pallor and are seen in patients who use snuff or chewing tobacco. There are significant regional differences in composition of smokeless tobacco products, and the relative risk ofdeveloping oral cancer among snuff dippers compared to non-tobacco users ranges from 1. Long-standing lesions have a leathery or velvety feel and represent leukoplakia arising within a smokeless tobacco lesion and are less likely than early lesions to regress on cessation of the habit. Generally, the bowel symptoms precede the oral lesions by about 1 year, although oral lesions may appear first. Hiatopathologic Featlres There is epithelial hyperplasia with marked spongiosis and the formation of suprabasilar clefts. Intraepithelial abscesses composed of neutrophils and numerous eosinophils are characteristic, and often there are similar abscesses in the edematous connective tissue papillae. A polymorphous inflammatory infiltrate is present in the lamina propria, sometimes in a perivascular distribution. Parakeratosis, atrophy of filiform papillae, and spongiotic pustules (in the absence of candida) characterize migratory glossitis. When located on mucosa other than the tongue, the terms "erythema areata migrans. Orofaclal granulornatosis Synonyms: Cheilitis granulomatosa, Miescber disease, MelkmsonRosenthal syndrome. Some investigators use this term to refer only to granulomatous inflammation not associated with other systemic conditions, such as Crohn disease or sarcoidosis, whereas others use it to designate a condition characterized by orofacial swelling that histologically consists of noninfectious granulomatous inflammation regardless of whether there is a known systemic etiology. Oral manifestations of the systemic conditions may predate systemic findings in up to half of patients with Crohn disease. Orofacial granulomatosis has been attributed to an abnormal immune response to a variety of antigens, including food and food additives as well as cinnamon products. The epithelium is acanthotic, with leukocyte exocytosis and often confluence of the rete ridges at the bases. There is edema of the papillary lamina propria, thinning of the suprapapillary epithelium, vascular ectasia, and a variable lymphoplasmacytic infiltrate, all features of psoriasiform mucositis. Pyostomatitil vegetans this is a rare, nonautoimmune, pustular, and vegetating mucosal disorder that is associated with inflammatory bowel disease (most often ulcerative colitis) in 50% to 70% of patients and is thought to represent the mucosal counterpart of pyodermatitis vegetans. There is also an association with liver diseases including sclerosing cholangitis. If the patient presents with the triad of cheilitis granulomatosa, fissured tongue, and facial nerve palsy, the diagnosis ofMelkersson-Rosenthal syndrome applies. Some consider cheilitis granulomatosa alone as the oligosymptomatic form of Melkersson-Rosenthal syndrome. These granulomas usually are present in small numbers and may be poorly formed, so multiple sections may be needed before they am be identified definitively. The surrounding tissues may be edematous and contain scattered chronic inflammatory cells, often in a peri- or paravascular location. If salivary glands are present, granulomas should be sought within the gland parenchyma. Stains for organisms are negative, and the granulomas should contain no identifiable foreign material Since the condition may wax and wane, the appearance of granulomas may not be demonstrable in all patients. Differential Diagnosis the granulomas of orofacial granulomatosis are indistinguishable from those of Crohn disease, and the patient should be evaluated for gastrointestinal signs and symptoms. Granulomas of sarcoidosis usually contain asteroid bodies and tend to be well formed. This is a common condition caused by mucous extravasation and pooling in the interstitium as a result of traumatic disruption of the integrity of the excretory salivary duct. This condition was first described in the early 1970s, and its etiology was putatively ascribed to a hypersensitivity reaction to a component of chewing gum. Superficial mucoceles are 2 to 3 mm blisterlike lesions located on the hard and soft palate. In the original chewing gum-associated cases, there was concomitant cheilitis and glossitis. In some idiopathic cases, there is accompanying supraglottic and laryngeal involvement with accompanying hoarseness and/or sore throat. A portion of the salivary duct, often exhibiting squamous metaplasia, the epithelium is markedly hyperplastic with spongiosis and sometimes superficial microcyst and pustule formation in a psoriasiform pattern. The lamina propria contains sheets of plasma cells that do not display atypia and are polycl. Dilated capillaries and scattered lymphocytes are noted in areu where the plasma cell infiltrate is less dense. Papillary structures comprising small vascular channels and fibroblasts protrude into the lumen. The absence of proliferation ofductal, myoepithelial, epidermoid, mucous, or dear cells differentiates a mucocele from a neoplastic process. Neaotizing sialometaplasia Neaotizing sialometaplasia is an uncommon inflammatory condition characterized by ulceration of the mucosa overlying infarcted salivary glands. It may be confused with a malignant process because of rapid onset, the clinical appearance, and histopathology. A cyst-like cavity is filled with mucus and surrounded by granulation tissue and histiocytes. Olnlcal Features may be present at the periphery, and the associated minor salivary glands exhibit varying degrees of chronic inflammation, ductal ectasia, acinar atrophy, and interstitial fibrosis (all signs of obstruction). In late stages, only a nodule of granulation tissue with occasional muciphages remains. Synovium-like villous projections may be present, and condensations of mucous leads to myxoglobulosis. The mucosa of the posterior hard palate and associated glands is affected in 70% to 80% of patients, with two-thirds of cases occurring unilaterally. The lesion usually begins as a swelling that ulcerates within days; pain may or may not be present After a few weeks, the mass of necrotic salivary gland tissue exfoliates, and rapid healing ensues. Hlstopethologlc Features the salivary glands exhibit preservation of their usual lobular architecture, and this is a very important feature present in all lesions, provided that an adequate biopsy is obtained. There may be extensive mucous pooling around acini even in early lesions with accompanying acute and -, ~ ~. Minor salivary gland acini undergo necrosis with preservation of their outlines; squamous metaplasia is also noted. In more advanced lesions, squamous metaplasia of the ducts and pseudoepitheliomatous hyperplasia of the overlying mucosa may be pronounced. Differential Diagnosis the preservation of the normal lobular architecture of the glands is an important histologic parameter that helps to distinguish necrotizing sialometaplasia from mucoepidermoid carcinoma and squamous cell carcinoma. In mucoepidermoid carcinoma, there is proliferation of mucous and squamous cells in a disorganized fashion, forming islands of tumor cells that vary in shape and size with infiltration of the adjacent structures. Squamous cell carcinoma exhibits significant cytologic atypia and pleomorphism with infiltration of the adjacent tissues, and the overlying epithelium exhibits dysplasia. In subacute necrotizing sialadenitis, the glands are diffusely infiltrated by a mixed inflammatory infiltrate with focal necrosis and little metaplasia. The nodule usually is dome-shaped, sessile or pedunculated, soft, mucosa-colored, and may show areas of ulceration and/or whiteness/keratosis. Focal areas of myxoid degeneration and mucinous change may Chellttis glandularis this is an unusual inflammatory condition of the lip (usually lower) of unknown etiology, although there is an association with actinic cheilitis, atopic diatheses, and factitial injury. Three clinical forms are recognized: simple, superficial suppururative (Baelz disease). Up to one-third of cases have been associated with the development of squamous cell carcinoma, although this may be a. Hlstopathologlc Featlres the glands contain a chronic interstitial inflammatory infiltrate with acinar atrophy, sialodoehitis, and often a purulent exudate within dilated and metaplastic ducts. Differential Diagnosis Distal obstruction of the salivary glands of the upper lip by sialoliths may give rise to similar inflammatory changes in the gland, although the sialoliths are identified. Flbroma Synonyms: Fibrous hyperplasia, fibroepithelial polyp, fibrovaseular polyp, bite fibroma, irritation fibroma. Although some fibromas may contain a few lipocytes, others contain significant amounts of fat, in which case a diagnosis of"fibrolipoma" is appropriate. Differential Diagnosis Clinical Features the palatal mucosa under the denture is covered by soft, pebbly, fibrous nodules that coalesce, resulting in a cobblestone appearance. Sclerotic fibromas are sharply circumscribed turnors that exhibit thick collagen bundles arranged in a storiform pattern and separated by prominent clefts. Other gingival epulides the term "epulis" refers to any growth on the gingiva or alveolar mucosa. Each of the first 4 entities arises as a reparative process in response to chronic irritation from deposits of dental calculus, poorly adapted dental restorations, orthodontic braces, or other local factors. They often occur on the marginal gingiva with at least a portion of the lesion resting against the teeth. Histopathologically, it is not unusual to see combinations of pyogenic granuloma, peripheral ossifying fibroma, and peripheral giant cell fibroma within one lesion because of common etiology. Medication-induced hyperplasias affect the gingiva diffusely over time and occur in 15% to 50% ofpatients taking phenytoin, calcium channel blockers, and cyclosporine. Its presence almost always indicates an underlying odontogenic infection within the bone.

Spitz nevi and tumors are recognized by characteristic architecture and enlarged monomorphous epithelioid or fusiform cells symptoms estrogen dominance order lithium 150mg online. Because of their localization to skin folds medications not to take during pregnancy cheap lithium 150mg line, axillary nevi commonly have polypoid or papillomatous surface topographies medications mothers milk thomas hale purchase genuine lithium online. Clinical Features Nevi of this type occur in females aged 6 to 54 years (median medicine in spanish buy cheap lithium on line, 26 years) symptoms 4 weeks pregnant order discount lithium online. Vulvar nevi range from 2 to 20 mm (mean treatment tendonitis buy 300mg lithium with visa, 6 mm; median, 5 mm) and commonly involve the labium majus, mons pubis, labium minus, clitoris, and perineum. Following the first report of atypical-appearing nevi on the scalps of children,249 there has been ongoing debate as to their biologic significance and relationship to "dysplastic" nevi and melanoma. Melanocytk nevi of the head and neck in close proximity to the scalp have comparable histologic features. However, a proportion of scalp nevi are clinically atypical, reflected in diameter larger than 5 mm, asymmetric, and have irregular and ill-defined borders and complex coloration. The nuclei are often enlarged with low-grade pleomorphism, readily observed nucleoli, and occasionally hyperchromatism. Thus, based on the latter findings, some degree of cytologic and architectural atypia is present in many of these nevi. Focal pagetoid melanocytosis and lentiginous melanocytic proliferation are uncommon, but papillary dermal ftbroplasia and lymphocytic infiltrates are frequent. Thus, the pathologist must have overwhelming criteria for melanoma in this age group, along with the concordance of learned colleagues. Uncommon findings in melanocytic nevi Unusual findings in, or presentations of, melanocytic nevil17. The color is most often dark brown or black, but considerable variegation of pigment is often noted. A speckled or mottled appearance is also common, and many have coarse, terminal hair follicles. It is believed that apparent immature, disordered morphologic patterns such as pagetoid spread, large irregular nests, and cytologic atypia diminish (or mature) with time. Up to 28% of acquired nevi may also exhibit nevus cells extending into the lower two-thirds of the reticular dermis. Near the epidermal surface, nevus cells tend to be aggregated in nests and may exhibit epithelioid cell features. Extension of nevus cells into the subcutaneous fat is also a common feature, particularly in larger varieties of congenital nevi. Probably the most characteristic feature is the diffuse proliferation of nevus cells throughout the reticular dermis with frequent extension into the subcutaneous fatvo,m,275. Foci of hypercellularity are also sometimes noted within the dermal population of cells. Neural differentiation resembling neural tubules or pseudo-Meissnerian structures may also occur. Congenital nevi with atypical features Archltectlral Disorder and Cytologlc Atypla All varieties of congenital nevi may exhibit varying degrees of architectural and cytologic atypia of both the intraepidermal and dermal components (Tables 27-14 and 27-15). Epithelioid cell lntraepidermal Pagetoid spread in nevi Dermal Expansile nodule of epithelioid cells Epithelioid schwannoma 2. Spindle cell with schwannian or perineurial differentiation Dermal Neuroid spindle cell tumor (neurofibroma-like) Schwannoma 4. Specific mesenchymal "ectomesenchymal") differentiation Cartilage Lipoma Hemangioma 6. They are usually sharply defined, symmetrical, round or oval, and often exhibit smooth to shiny surface. Usually, the melanin does not have the finely divided ("dusty") character observed in melanoma cells. Most of these nodular cellular aggregates tend to show gradual transition (not abrupt) with the surrounding nevus. Cytological atypia, increased proliferative activity, and necrosis are not usually observed. If cytological atypia is present, the melanocytes are often uniform and mitotic activity in minimal. However, significant cytologic atypia, conspicuous mitotic activity (eg, up to 25 mitoses per mm2), ulceration, and necrosis may be observed in rare lesions. Hfstopathologlc Features Microscopic examination discloses nodules of uniform spindle cells with neuroid/schwann. Neither significant cytological atypia, mitotic activity, nor necrosis is observed. The latter lesion may be asymptomatic or result in hydrocephalus (either the communicating or noncommunicating type), seizures, mental retardation, other neurologic signs, or leptomeningeal melanoma. Meningeal biopsy may be necessary to confirm a diagnosis of leptomeningeal melanoqtosis. I proliferations that often involve the papillary dermis, resulting in a compound news. However, in general, the pattern within the epidermis has an orderly character, and many of the cells do not reach the granular layer. Furthermore, careful examination reveals low-grade or no cytologic atypia of these cells. Virtually all of these proliferations are benign and represent mimics of melanoma. The overwhelming majority of theae nodular proliferations, particularly in the neonatal period, are biologically benign mimics of melanoma. D4 Such tumors usually manifest cohesive cellular nodules distinctly different from the surrounding nevus, substantial nuclear pleomorphism, necrosis, mitotic activity, and striking cellularity. Melanomas developing in newborns and infants younger than 1 year ofage are extremely rare, and such a diagnosis must always be seriously questioned. A prudent approach is to ensure complete surgical removal of such nodular lesions and to carefully monitor the patient for recurrence or metastasis. The cells are closely crowded; have minimal cytoplasms; and contain small round or slightly oval nuclei with dense, uniformly dispersed chromatin. The cells take on the appearance oflymphoblastic lymphoma or comparable blastic" tumors. The distinction from melanoma relates to the gradual blending of the cellular nodule with the surrounding nevus. Necrotic cells, significant cytologic atypia, and easily found mitotic activity are also features suggesting melanoma. Nonetheless, age is a critical factor to be considered in the evaluation of these proliferations. A diagnosis of melanoma should be made with extreme caution in children younger than age 1 year. De novo melanomas arising at birth (congenital melanoma) or in prepubertal individuals. Melanoma metastatic to the fetus from the mother constitutes an extremely rare type of congenital melanoma. Neonates usually present at birth with widespread visceral metastases and are dead of disease within days to months. Melanomas arising in congenital nevi, usually (but not exclusively) of large and giant types at birth, in childhood, and sometimes in older individuals. These may be seen in patients of all ages but are exceptionally rare under the age oflOyears. Conventional adult-type melanomas, usually with epithelioid cell phenotype corresponding to superficial spreading" and nodularD subtypes in adults. The Spitz nevus has been recognized for well over a century but was first definitively characterized in 1948 by Sophie Spitz. Since that time, Spitzoid melanocytic neoplasms have continued to occupy a special niche in the melanocytic neoplastic system, and recent molecular genetic findings provide support for their unique biological nature. Yet there are still substantial unresolved questions concerning their molecular characterization and relationship with other melanocytic lesions, natural history, and biologic potential. Histologically, Spitzoid melanocytic neoplasms are defined by large epithelioid and/or spindled cells with distinctive architecture. The term "Spitz nevus" connotes lesions lacking atypical features and with very low risk of neoplastic progression. Multiple Spitz nevi may occur in either a grouped (agminate) or disseminated pattern. They usually contain junctional nests/fascicles of large epithelioid cells, spindle cells, or both, usually extending from the epidermis into the reticular dermis in a wedgeshaped configuration. J20 the junctional nests often show clefting and separation from the surrounding epidermis. Base of Spitz tumor shows orderly infiltration of collagen by individual cells (maturation). A hyperplastic epidermis and vertical orientation of junctional nests of spindled melanocytes contribute to the so-called raining-down appearance. Pagetoid melanocytosis in the epidermis, if present, is usually focal, sparsely cellular, and limited to the center, versus the periphery, of the lesion and the lower half of the epidermis. Ju Additional intraepidennal findings may include discohesive junctional melanocytic nests, transepidennal elimination of entire nests of melanocytes, and Kamino bodies (eosinophilic hyaline globules). There is usually also a corresponding transition from larger to smaller cells and nuclei. Spitz nevi and its variants have a propensity to involve hair follicles and eccrine ducts. In most instances, intraepidermal fascicles of cells track along the adventitial sheaths of appendageal structures into the papillary dermis and often into the reticular dermis. The majority of Spitz nevi (~66% or more) are compound, 5% to 10% are junctional, and 12% to 20% are dermal. Overall, the mitotic rate in conventional Spitz nevi is low (usually S2 mitoses/mm1), or mitoses are absent1111,320,3u Mitoses are rare or absent in the deep dermis. They are often asymmetrical and not well circumscribed, may show effacement/consumption of the epidermis, and may be ulcerated. Hypercellular, well-defined, and reasonably symmetrical nodular tumor at scanning magnification. The lesion has the silhouette of a conventional melanocytic nevus with architectural disorder and cytological atypia but exhibits the cytological characteristics of a Spitz tumor. Mitoses located at the deep margin (advancing front) also raise concern for malignancy. In contrast, a Ki-67 proliferation index value >20% suggests the possibility of melanomal" although. Pagetoid Spitz nevus Clinical Features A distinctive variant is the mainly intraepidermal subtype with a prominent pagetoid pattern. The most important reason for recognizing this lesion is its frequent misdiagnosis as in situ or microinva. Many of these lesions show a combination of both a single cell and nested proliferation of epithelioid melanocytes. The single-cell proliferative pattern is often both basilar and pagetoid and commonly varies within the lesion. Typical junctional nests of epithelioid cells with associated clefting are also usually present and may be quite small in size. Suspicion for melanoma should be especially high in the presence of multiple major criteria, including age >10 years, and particularly >40 years; increased lesional diameter, particularly >1 em; ulceration; mitotic rates >2 mitoses/mm2, and particularly >6 mitoses/ mm2 528; and involvement of subcutaneous fat. Other important criteria are asymmetry; poor circumscription; increased cellularity of the lesion; diffuse, full-epidermal thickness and peripheral pagetoid spread; diminished or absent maturation of the dermal component; angi. Certain immunomarkers and genomic alterations detected by array comparative genomic hybridization, next-generation sequencing. The cells are polyangular and contain abundant groundglass cytoplasm, and the nuclei have dispersed chromatin. Of particular importance are the cytologic characteristics of the epithelioid cells; they tend to be fairly monotypic with abundant pinkish cytoplasm that has a ground-glass appearance rather than the granular cytoplasm often observed in melanoma cells. The nuclei of Spitz nevus cells are also fairly uniform with evenly dispersed chromatin versus the pleomorphism of melanoma cells. Nonmelanocytic lesions that need to be considered in the differential diagnosis include cellular neurothekeoma, solitary xanthogranuloma, epithelioid cell histiocytoma, and solitary reticulohistiocytoma. Clinical Features Desmoplastic Spitz nevus typically presents as a firm, domeshaped, flesh-colored papule or nodule, measuring up to 1 cm in greatest diameter; is most often located on the extremities, especially the upper arm; and suggests a dermatofibroma (Table 27-21). Histopathologic Features Spitz tumors and lymph node involvement Spitz tumors may spread to loco-regional sites as satellite (including microscopic satellite), in transit, and lymph (including sentinel) node metastases. The desmoplastic changes in Spitz nevi may make up the entire lesion or any portion of it. Cytologically, Other variants of Spitz news Other noteworthy variants of Spitz nevus reported in the literature include desmoplastic, pigmented spindle cell, angiomatoid (related to desmoplastic Spitz nevus and characterized by prominent vascularity),345 hyalinizing (hyalinized dermis),346 halo (dense lymphoid infiltrates), ~ plexiform,3411 recurrent or persistent (may have tumoral dermal component suggesting melanoma),349 and tubular (prominent intracellular vacuoles, possibly an artifact) variants, and so on350 (see Table 27-20). Nonmelanocytic dermal spindle cell lesions that may share morphologic features of desmoplastic Spitz nevus are dermatofibroma, epithelioid cell histiocytoma, and solitary reticulohistiocytoma. Pigmented splndle cell nevus Synonyms: Pigmented spindle cell nevus of Reed, pigmented spindle cell tumor, Reed nevus. The size of the nuclei tends to diminish as melanocytes approach the base of the lesion, which is usually ill defined. Histologically, whereas desmoplastic Spitz nevi tend to be small, well-circumscribed, superficial lesions.

Spindle cell lipomas with prominentvascularity may be similar but present in older individuals symptoms 8 days after iui lithium 150mg lowest price, are solitary medicine 750 dollars generic lithium 300 mg visa, and have organiud arrays of spindle cells oft treatment jammed finger generic lithium 150mg line. Hlstopathologrc Featlres Grossly medicine ketorolac cheap lithium 300 mg with mastercard, the lesions are generally circumscribed and average 4 cm in siu (range 2-29 cm) treatment quotes buy lithium 300mg with amex. Bland spindled cells with stubby nudei admixed with adipocytes and characteristic ropey collagen symptoms graves disease buy 300mg lithium overnight delivery. The background may exhibit abundant ropey collagen and rare mature adipocytes (A), or may be variably myxoid (B). The differential diagnosis varies according to the cellularity of the lesion, the amounts of other components (eg, myxoid material, vessels), and the presence or absence of pleomorphic floret cells. Cellular cases may be mistaken for atypical lipomatous tumor/well-differentiated liposarcoma, which may contain thick bundles ofcollagen but has a less uniform appearance, with large atypical cells embedded within fibrous septa. Solitary fibrous twnors may contain mature adipose tissue (fat-forming solitary fibrous tumor) and exhibit a similar immunohistochemical profile. In addition, the spindle cells of solitary fibrous twnor are more often curved rather than straight, do not form discrete fascicles, and are usually not associated with either ropey collagen or a myxoid background. However, the latter twnor additionally demonstrates multiple gains and losses of genetic material. Patients present with a slowly growing, painless, circumscribed mass (1-11 cm) located subcutaneously, within fascia, or intramuscularly. The proximal limbs/limb girdles are most commonly affected; the head and neck are less common sites. Vacuolated cells simulating lipoblasts arranged in nests admixed with adipocytes within a myxochondroid matrix. Chondromas ofsoft tissue lack adipose tissue and have mature hyaline cartilage as well as multinucleated giant cells. Mixed tumors may contain fat, but they also contain keratin-positive myoepithelial cells that often form glands and epithelial cords. Myxoid liposarcoma is distinguished by its characteristic "chicken-wire" vasculature, uniform myxoid background. Extraskeletal myxoid chondrosarcomas are also typically large twnors that display prominent hemorrhage and a lack of circumscription. If indicated, molecular studies can assist in distinguishing chondroid lipoma from its translocati. Myollpoma Clinical and Histopathologic Features Myolipoma is an uncommon neoplasm occurring in the deep soft tissues of adult women, only infrequently arising in the subcutaneous tissue. The vacuolated cells often have prominent cytoplasmic borders resembling chondroblasts. In some areas, the vacuolated cells fonn cords superficially resembling myxoid chondrosarcoma. Chondroid lipoma is highly vascular and may exhibit degenerative changes, including hemorrhage, fibrosis, and inflammation. The muscle cells form only short, irregular fascicles, in contrast to the long fascicles present in leiomyomas. Typical triphasic histology exhibiting mature adipoc:ytes, smooth muscle, and thickwalled blood vessels. Histopathologic Featlres Angiomyolipomas exhibit a distinctive triphasic histology, with thick-walled blood vessels, lipid-distended tumor cells (so-called adipocytes). The spindle cells of spindle cell lipoma have scant cytoplasm and are not immunoreactive for actin or desmin. Those that have undergone maturation lack significant numbers of lipoblasts and may be composed entirely of mature adipose, mimicking myolipoma. The age of the patient and the presence of an adjacent conventional lipoblastoma are helpful in this instance. These tumors share a distinctive cell type-the perivasc:ular epithelioid cell, which has no known normal tissue counterpart. M Although angiomyolipoma is characterized by a triphasic histology, oc:casionally, one of these components may predominate with exclusion of one or more other elements. Immunohistochemical staining for melanocytic markers can be useful for such cases. Theyariseusuallyinyoung to middle-aged adults (average age 38 years) and are most commonly located in the thigh, followed by the trunk. They are most often subcutaneous, well circumscribed, and measure up to 20 an in diameter (mean 10 cm). Foci of brown fat can be present in an otherwise typical mature lipoma, but there is no established threshold for separating these cases from hibernoma. Hibernomas may be mistaken for liposarcomas, but the uniformity of the lesion, lack of mitoses, lack of atypia, and (most importantly) lade of true lipobl. Slightly larger cells with multiple cytoplasmic vacuoles that do not indent the centrally placed nucleus are also present. The typical hibernoma is composed of the aforementioned three cell types in varying proportions. The lipoma-like variant consists of only scattered hibernoma cells among white fat cells. The spindle cell variant combines the features of hibemoma and spindle cell lipoma (note: these cases probably represent spindle cell lipomas with brown fat cells). The importance of these variants lies only in their recognition, not in their clinical behavior. There is a higher prevalence among Mediterranean individuals, and there is a strong relationship to alcoholism. Also, extensive involvement of both the subcutis and muscle usually distinguishes a large intra/intermuscular lipoma from lipomatosis. Upoblastoma or llpoblastomatosls Cllntcal Features Lipoblastoma or lipoblastomatosis is a rare tumor recapitulating embryonic development of adipose tissue that occurs almost exclusively in children younger than age 7 years, predominantly in those younger than age 3 years. Localized forms are termed "lipoblastoma," and diffuse forms are called iipoblastomatosi. In subcutaneous sites, localized lobulated lesions smaller than 5 an in diameter are most common. Incomplete resection is common in the diffuse form owing to its infiltrative nature. Mixture of granular eosinophilic cells, multivacuolated cells, and mature adipocytes. Unfortunately though, the most common type of liposarcoma affecting children and adolescents is conven- Clinical Features Infants, young children Extremities, trunk Localized or diffuse tional myxoid liposarcoma. Histologic observations and genetic studies over the past decade have been successfully integrated. The lesions closely mimic well-differentiated or myxoid liposarcomas (Table 32-7). At high power, numerous lipoblasts, a rich plexiform capillary network, and a myxoid matrix resemble myxoid liposarcoma. Maturing lipoblastomas display few lipoblasts but still have distinct lobularity and possibly increased vascularity. Molecular Genetics Liposarcoma Liposarcoma is the most common soft tissue sarcoma in adults and accounts for approximately 20% of all mesenchymal malignancies. Similarly, the entity formerly known as "round cell liposarcoma" is now regarded as a higher-grade manifestation of myxoid liposarcoma. Fibrous septa dividing the fatty tumor into lobules with varying degrees of maturation. Importantly, the presence of lipoblasts is neither necetsary nor sufficient to make a diagnosis of liposarcoma. Lipoblasts are strictly defined by the presence of single or multiple discrete, optically clear, round and sharply demarcated cytoplasmic vacuoles that indent an enlarged hyperchromatic nucleus. Although not clinically or prognostically important, histologic variability is important for the pathologist to recognize. The sclerosingvariant exhibits areas of increased collagen (fibrillary or hyalinized) with less obvious lipogenic differentiation; these collagenou. In the inflammatory variant, mixed acute and/or chronic inflammation infiltrates the tumor and obscures the enlarged, hyperchromatic cells. Terminological preference depends heavily on liaison between surgeon and pathologist. Subcutaneous tumors are well circumscribed, 2 to 20 cm in diameter (mean 10 cm), and have a predilection for the upper and lower limb girdles. However, dedifferentiation may take place, with subsequent metastatic competence in deep, and rarely superficial. Benign mimics include lipoma, spindle cell/pleomorphic lipoma, lipoblutoma, xanthomatous reactions, fat necrosis, and diffuse neurofibroma. Spindle cell/pleomorphic lipomu have a rather well-defined clinical context (see the preceding text). Lipoblastoma may be considered, but they generally occur in children younger than 7 years of age, when the diagnosis of liposarcoma is highly unlikely. Xanthomatous reactions and fat necrosis both have foamy histiocytes rather than cells with large, fat vacuoles (adipocytes); are associated with inflammation; and lack nuclear enlargement with hyperchromasia. Recognition of the atypical adipocytes is most important for the correct diagnosis. The dedifferentiated component is often a high-grade sarcoma but may also be a low-grade spindle cell or myxoid sarcoma. Some are composed mainly ofdedifferentiated areas with minimal or absent well-differentiated tumor. Homologous dedifferentiation also occurs, consisting of scattered lipoblasts or sheets of pleomorphic lipoblasts resembling pleomorphic liposarcoma. A prominent myxoid component and rich vascularity can simulate myxoid liposarcoma or myxofibrosarcoma. The potential for heterologous differentiation within dedifferentiated liposarc:oma further complicates this matter. Those with more low-grade appearance may be confused for leiomyoma/leiomyosarc:oma and dermatofibrosarcoma, while those with more high-grade histology should be differentiated from pleomorphic: rbabdomyosarcoma and metastatic melanoma. Identification of a well-differentiated component or immunohistoc:hemistry for I r. Myxoid liposarcoma is unique in that metastases tend to occur in unusual soft tissue sites, such as the extremities and chest wall, rather than the visceral organs. Frequently, the myxoid matrix may coalesce to form acellular pools with an alveolar appearance. Myxoid liposarcoma typically lacks nuclear pleomorphism, giant tumor cells, and prominent spindling. Round cell b:ansformation in my:mid liposarcoma is characterized by a significant increase in cellularity, with nuclear overlapping and obscuring of the capillaries (Pig. The cells are smaller than adipocytes, with enlarged hyperchromatic nuclei and prominent nucleoli. Despite the aggressive nature of the lesion (including eventual metastasis in more than 5096 of patients), mitoses are usually sparse. Myxomas are less cellular, lack the vascular network, and do not contain lipoblasts. Angiomyxomas lack lipoblasts and are characterized by numerous isolated vessels rather than a plexiform. However, the vessels are not as profuse and are typically thicker and straighter than those in my:r. In addition, lipoblasts are not present (even though pseudolipoblasts can be numerous), and the lesion often has a distinctly multinodular growth pattern. When a tumor is purely round cell, the diagnosis may be very difficult and requires a thorough search for lipoblasts. Fluorescence in situ hybridization may be useful in diagnostically challenging cases. Numerous pleomorphic multivacuolated lipoblasts, some with frankly anaplastic nuclei. Pleomorphlc liposarcoma Clinical Features Pleomorphic liposarcomas are the least common type of liposarcoma. They occur most often in elderly individuals, and superfidal examples are especially rare (Table 32-11). Histopathologic Features these tumors generally exhibit 3 morphologic pictures: (1) a high-grade pleomorphic spindle cell sarcoma containing scattered multi. The epithelioid morphology in these pleomorphic tumors may closely simulate other malignant epithelial neoplasms, mainly adrenal cortical carcinoma. Inhibin immunoreactivity, however, has not been reported in pleomorphic liposarcoma. Even within the cutaneous compartment alone, there are site-related differences in biologic potential. For example, extremely bland lesions of the genital region may still carry a risk for recurrence, which may occur late. Alternatively, histologically malignant smooth muscle tumors that are confined to the dermis usually behave in a benign fashion. It occurs on the trunk or extremities as a patch or plaque measuring up to 10 cm in diameter. Irregularly arranged smooth muscle bundles in the reticular dennis are interspersed with collagen, adipocytes, and adnexa.

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