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Several reactive cystic lesions can also produce tumor-like mass, such as lymphoepithelial cyst, keratinous cyst, mucocele, salivary duct cyst, polycystic (dysgenetic) disease of parotid glands, and sclerosing polycystic adenosis. Lin B T, Weiss L M, Medeiros L J 1997 Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors. Immunohistochemically, schwannomas show diffuse and strong S-100 protein positivity. E, Solid to trabecular growth pattern with prominent interspersed hyaline material. Williams G D, Hoffman S, Schwartz I S 1984 Malignant transformation in a plexiform neurofibroma of the median nerve. However, most cases have a relatively bland cytologic appearance, and the diagnosis of malignancy is based solely on the identification of infiltrative growth. A, the tubules are lined by ductal cells only, without an underlying layer of basal or myoepithelial cells. The epithelial tumor cells are positive for keratin antibodies, a finding that facilitates the diagnosis. Sometimes the basaloid cells appear plump and spindled, streaming in the longitudinal direction of the tumor islands. Despite the discovery of numerous molecular and cytogenetic markers, cell type remains an independent prognostic factor in most studies. Clinical Features Salivary duct carcinoma most frequently affects the elderly (peak incidence at sixth and seventh decades), with a male to female ratio of 3 to 6: 1. Autonomic Nerve Tumor (Plexosarcoma, Gastrointestinal Autonomic Nerve Tumor) Autonomic nerve tumors have, in the past, been regarded as a distinctive group of intra-abdominal neoplasms, thought to arise from the myenteric plexus of the gastrointestinal tract and defined by their ultrastructural features. This classification does not have clinical importance but serves to alert pathologists to the variable appearances of this seemingly monotonous tumor. The tumor cells are typically arranged in a prominent nesting pattern and show an epithelioid appearance with moderate amounts of eosinophilic cytoplasm, round nuclei with prominent nucleoli, and frequent mitotic figures. Currently, no definitive histologic criteria exist to make the diagnosis of an oligoastrocytoma. Arguably, the presence of nodal metastasis with extranodal extension of carcinoma represents the most important biologic predictor, associated with increased locoregional disease and distant metastasis. The solitary tumors can be found on any portion of hairbearing skin, but the head and neck are the most common sites. Recurrent lesions quite often show maturation toward the appearances of a simple lipoma. Some primary optic nerve meningiomas may appear calcified on imaging studies, a reflection of a high number of psammoma bodies. White patients with congenital melanosis oculi may be at risk of the development of uveal melanoma, not conjunctival melanoma. Scott M P, Helm K F 1999 Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma. B, the tumor is composed of compact packets and trabeculae of polygonal cells with abundant eosinophilic granular cytoplasm. Occasional mitoses are seen, but pleomorphism is absent, although isolated cases may show mild nuclear hyperchromasia, which is probably degenerative. Admixed with these cells are scattered bizarre, often multinucleate stromal cells and variably prominent fibrous septa containing hyperchromatic spindle cells and occasional bizarre cells. Ariza A, Bilbao J M, Rosai J 1988 Immunohistochemical detection of epithelial membrane antigen in normal perineurial cells and perineurioma. Smith T A, Machen S K, Fisher C, Goldblum J R 1999 Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor. In general, local recurrence and regional lymph node metastasis are relatively frequent, occurring in nearly half of the reported cases. C, A more extreme degree of coalescence results in the formation of large islands predominated by clear cells.

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Although typically encapsulated, they lack the Antoni A or B zonation or hyaline vessels of conventional schwannoma and consist of nests or trabeculae of eosinophilic epithelioid cells, often in a myxoid stroma. Laryngeal paragangliomas are quite rare but do occur,79-82 associated with the superior laryngeal paraganglia located in the false vocal cord region or, more rarely, the less consistently positioned inferior laryngeal paraganglia, located subglottically in the cricothyroid or cricotracheal region, in rare instances associated with the capsule of the thyroid gland. Rarely, an osteosarcoma is small and extremely well circumscribed, suggesting a benign lesion. This unusual variant may be included in the spectrum of low-grade sebaceous tumors. Histologically, the epineurium of the affected nerve is expanded by copious, poorly circumscribed, mature fibrofatty tissue. Perivascular pseudorosettes, true rosettes, and tubules are present to varying degrees. Marked myxoid change of the matrix and invasion of surrounding tissue should be considered signs of malignancy. Harwood T R, Gracey D R, Yokoo H 1976 Pseudomesotheliomatous carcinoma of the lung. The tumors contain areas of typical sebaceous lymphadenoma juxtaposed to a frankly malignant component; the latter lacks the characteristic lymphoid stroma and can be a sebaceous carcinoma, undifferentiated carcinoma, adenoid cystic carcinoma, or epithelial-myoepithelial carcinoma. Cancer 32: 830837 Matsukuma A, Enjoji M, Toyoshima S 1991 Ductal carcinoma of the breast. A background lymphocytic infiltrate either as individual cells or in clusters can be identified throughout the tumor and often in a perivascular (cuffing) location; occasional germinal centers can be identified. Arch Pathol Lab Med 113: 1147-1150 Reingold I M, Amromin G D 1971 Extraosseous chondrosarcoma of the lung. Also, this technique affords the possibility of detecting chromosomal rearrangements, most of which have intron breakpoints and therefore are invisible to whole exome or targeted sequencing approaches. The lesion has a sclerotic, undulating border that gives rise to a scalloped appearance. The character of the cut surfaces is highly variable, often reflecting the predominant histologic variant, such as a gritty texture in cases with abundant psammoma bodies or a more lipidic quality with the secretory type. Retinoblastoma histopathologic features may generically reflect aggressive biologic behavior. Sundararajan V, Robinson-Smith T M, Lowry A M 2003 Duodenal gangliocytic paraganglioma with lymph node metastasis: a case report and review of the literature. Grossly, the tumors are well circumscribed and can measure up to 5 cm in diameter. Membranous basal cell adenoma (also known as dermal analogue tumor) is histologically identical to dermal cylindroma. Lesions of the small bones of the hands and feet that contain giant cells are more likely to be other conditions, such as aneurysmal bone cyst, rather than giant cell tumors; however, true giant cell tumors do occur in the small bones of the hands and feet. Very occasionally, the epithelium may form goblet or mucous cells, which in association with squamous epithelium can lead to an erroneous interpretation of mucoepidermoid carcinoma. This villous architecture is appreciated better if the specimen is immersed in water. Alveolar cases may also, albeit less frequently, show anaplastic features or rhabdoid inclusions, as described in embryonal tumors earlier. Ann Diagn Pathol 6: 349351 Palacios J, Sarrio D, GarciaMacias M C 2003 Frequent Ecadherin gene inactivation by loss of heterozygosity in pleo morphic lobular carcinoma of the breast. Primary malignant giant cell tumor is a rare tumor in which areas of synchronous high-grade sarcoma are associated with benign giant cell tumor. The central cyst contains orthokeratotic, lamellar keratin, and the lining has prominent granular cell layers. The rare oncocytic variant (oncocytes accounting for >60% of the cell population) can potentially be confused with oncocytoma or oncocytic carcinoma. With possible exceptions, such as subcutaneous lipomas or benign smooth muscle tumors, very little evidence exists that these lesions arise from their mature (differentiated) tissue counterpart. Up to 15% may retain communication with the frontal lobes through an osseous defect, either by a vestigial fibrous cord or as a true encephalocele. Mediastinoabdominal lipomatosis36 also is associated with alcohol abuse, hyperlipidemia, and maturityonset diabetes.

Diseases

• Macules hereditary congenital hypopigmented and hyperpigmented
• Sakati syndrome
• Oculomaxillofacial dysplasia with oblique facial clefts
• Triosephosphate isomerase deficiency
• Maxillofacial dysostosis
• Xanthomatosis cerebrotendinous
• Fanconi anemia type 1

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The spindle cell lesions appear to be molecularly distinct from other forms of well-differentiated liposarcoma89,90 and may ultimately be reclassified. Wind J J, Caputy A J, Roberti F 2008 Spontaneous encephaloceles of the temporal lobe. However, this depends largely on the tumor size in this region, as well as on the presence of other tumors (hemangioblastoma, renal cell carcinoma) as part of this syndrome. Abramson A L, Steinberg B M, Winkler B 1987 Laryngeal papillomatosis: clinical, histopathologic and molecular studies. Nodular fasciitis,130-133 in its prototypical form, presents as a rapidly enlarging, often painful or tender subcutaneous nodule, most often affecting young adults and showing a predilection for the upper limb, especially the forearm. Ophir D, Marshak G, Czernobilsky B 1987 Distinctive immunohistochemical labeling of epithelial and mesenchymal elements in laryngeal pseudosarcoma. Posterior extension from the maxillary sinus toward the nasopharynx may result in obstruction of the nasopharynx and clinical suspicion of a primary nasopharyngeal tumor. Mucinous carcinoma should be distinguished from a mucocelelike lesion and myxoid fibroadenoma. Unfortunately, it is not always known at the time of initial diagnosis whether a dermal component or deepseated primary carcinoma is present and this can be difficult to sort out unless special methods are used. Suster S, Moran C A 1995 Unusual manifestations of metastatic tumors of the lungs. Fine E D, Dahms B, Arnold J E 1995 Laryngeal hamartoma: a rare congenital abnormality. The lymphoid infiltrate apparently begins in the periductal areas and gradually replaces the lobules. Admixed with these are mononuclear epithelioid cells, histiocytes, and mixed inflammatory cells. Keratin may be observed in microcavities; when this occurs, it is usually parakeratotic and is often associated with microabscesses. The nuclei are susceptible to crushing artifact resulting in deformation and clumping of nuclei, as well as diffusion of chromatin material. Even histologically, a borderline melanocytic uveal lesion is never described as atypical melanocytic hyperplasia. Lymphoepithelial carcinoma of salivary gland is morphologically identical to its counterpart occurring elsewhere in the body. Tumors that are predominantly composed of one type may be designated as fibrillary, protoplasmic, and gemistocytic variants, but these cell types are usually intermixed in the same neoplasm, without any particular prognostic importance. Lymphoma When lymphoma involves the skeleton, it most commonly does so as a component of widespread disease, taking the form of multiple destructive lesions or diffuse marrow infiltrates. Although cutaneous and conjunctival melanomas originate in an epithelial compartment, uveal melanomas originate in mesenchymal compartments-the choroid, 2086 ciliary body, and iris-and there are therefore no counterparts to in situ melanoma in the uvea. Price S K, Kahn L B, Saxe N 1993 Dermal and intravascular fasciitis: unusual variants of nodular fasciitis. The basaloid cells, in comparison with those seen in the cribriform and tubular patterns, usually exhibit more significant nuclear pleomorphism and mitotic activity. The great majority of lesions given this label are in fact simply nodules of physiologic lobular proliferation that become more prominent than the adja cent breast tissue and may appear clinically to be a dis tinct mass. Kato N, Yasukawa K, Onozuka T 1998 Primary cutaneous adenoid cystic carcinoma with lymph node metastasis. Cassarino D S, Derienzo D P, Barr R J 2006 Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification- part two. High-grade tumors comprise lesions showing marked cellularity with nuclear pleomorphism and atypia, high mitotic activity (average 8-12 mitoses per 10 hpf), abundant necrosis, and hemorrhage. Rawlinson D G, Herman M M, Rubinstein L J 1973 the fine structure of a myxopapillary ependymoma of the filum terminale. However, if the tumor has broken through the cortex to involve soft tissues, the neoplasm is considered to involve two compartments. The incidence of lobular neoplasia has increased with mammographic screening, and associated micro calcification may rarely be present, but the changes of lobular neoplasia are generally a chance finding rather than the specific cause of the mammographic abnormality. The intertrabecular spaces contain proliferating spindle cells that lack cytologic atypia.

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Pleural synovial sarcomas exhibit the same histologic, immunohistochemical, ultrastructural, and cytogenetic features as synovial sarcomas in other locations (see Chapter 24). The microcystic pattern is the most characteristic growth pattern, although it is not invariably present. This pattern differs from the hyalinization seen in pleomorphic adenoma in that the process is confined to the cellular island, which itself is sharply delineated from the fibrous stroma. Histologically, Langerhans cells have an oval nucleus surrounded by pink or clear cytoplasm. Although some indi vidual prognostic factors may be extremely powerful, it is now clear that combining the results of a range of prognostic variables in the form of an index can give a high level of accuracy of prediction of prognosis, which can then be used to distinguish groups of patients suitable for different forms of therapy. Bourguin A, Tung R, Galili N, Sklar J Rapid, nonradioactive detection of clonal T-cell receptor gene rearrangements in lymphoid neoplasms. Psammoma bodies can occasionally be encountered in these areas but are of no diagnostic significance. Hanau C, Miettinen M 1995 Solitary fibrous tumor: histological and immunohistochemical spectrum of benign and malignant variants presenting at different sites. Ann Diagn Pathol 2: 1-11 Addis B J, Hyjek E, Isaacson P G 1988 Primary pulmonary lymphoma: a reappraisal of its histogenesis and its relationship to pseudolymphoma and lymphoid interstitial pneumonia. Therefore idiopathic midline destructive disease is not a specific term and should never be used to indicate a diagnosis of a malignant lymphoproliferative neoplasm. Multiple cartilaginous lesions are present, consistent with multiple enchondromas. By severing the lateral canthal ligament (a trivial surgical maneuver), surgeons are able to resect nearly half of the lower eyelid and still accomplish primary closure. However, the cellular proliferation may be focally arranged in ribbons or cords admixed with rosettelike structures, giving the lesion a vaguely neuroendocrine appearance. Parl F F, Richardson L D 1983 the histologic and biologic spec trum of tubular carcinoma of the breast. Nutritional deficiencies such as iron, folate, or vitamin B12 can also simulate dysplasia. Infrequently, myxopapillary ependymomas present as extradural lesions in the presacral or retrosacral soft tissues, presumably arising from ependymal rests (see also Chapter 27 for soft tissue counterpart). Medicine 61: 317-329 Grogan T M, Spier C M 2001 B cell immunoproliferative disorders, including multiple myeloma and amyloidosis. The normal serous cells show moderate apical membranous staining, and the distal intercalated duct cells show variable weak to moderate apical staining. Furthermore, immunoglobulin genes (but not T-cell receptors) accumulate point mutations within the rearranged V segment as the B cells pass through the germinal centers of lymph nodes-a process that also diversifies immunoglobulin structure. The overexpression of cyclin D1 can be detected immunohistochemically and used diagnostically to distinguish mantle cell lymphoma from other B-cell lymphomas. Odontoameloblastoma this very rare tumor shows odontoma formation in association with an otherwise conventional ameloblastoma. Whole exome sequencing involves capturing each exon in the genome with a targeted capture molecule, and then analyzing the entire coding sequence. Histologically, the tumor invades the surrounding parenchyma in broad fronts, resulting in multiple tumor nodules separated by sclerotic stroma. Tumors with round cell morphology sometimes show eosinophilic rhabdoid cytoplasmic inclusions. Statistically, the risk of melanoma recurrence appears greater in patients who have had in situ lesions with regression. The tumor may have an infiltrative growth pattern within smooth muscle, but this does not indicate malignancy; despite the fact that several cases of regional lymph node involvement have been reported suggesting malignant potential,88-90 most patients do well after surgical resection. Kowalski P J, Paulino A F 2001 Proliferation index as a prognostic marker in hemangiopericytoma of the head and neck. In occasional cases, wreaths of epithelioid histiocytes surround the lymphoepithelial lesions.

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Primary breast adenocarcinoma may also metastasize to the contralateral breast or ipsilateral breast if conservation therapy has been used. Extending from the surface are narrow to broad, vertically oriented to convergent cords of squamous cells that are blunt at their deepest extent. However, all points on the spectrum share a predominantly lobular, or sometimes trabecular, growth pattern. Ganglioneuroblastoma Ganglioneuroblastoma is an exceedingly rare tumor of lung (see Chapter 28). Nguyen Q A, Gibbs P M, Rice D H 1995 Malignant nasal paraganglioma: a case report and review of the literature. A, the basic neoplastic unit comprises discrete tubules lined by an inner layer of ductal cells with eosinophilic cytoplasm and an outer layer of large clear myoepithelial cells. We further recognize that foci of sebaceous cells may be observed in a variety of basaloid tumors, including basal cell carcinomas, cylindromas, and spiradenomas. Cancer 70: 2099-2104 Wright J D, Font R L 1979 Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations. The mononuclear cells show close immunophenotypic similarities to normal synoviocytes,360 which are thought to be closely related to histiocytes. Urate crystals provoke an inflammatory response from leukocytes and synovial cells, as urate is phagocytosed by monocytes. Macroscopic Features Typically a poorly defined firm graywhite mass is seen, but sometimes the appearance is like normal fibrous breast tissue. This is often associated with obviously increased mitotic activity, and it is important to recognize that this is disproportionate to the degree of dysplasia. The neoplastic infiltrate may be accompanied by a mixed inflammatory cell population. Additional patterns of small islands, net-like ribbons or trabeculae, alveolar nests, or mixtures of these may coexist in any given tumor. The mesenchymal stromal component in mixed tumors is characterized by loose chondromyxoid tissue and more rarely by the formation of cartilaginous matrix. Other demographic trends include an increased incidence of lung cancer in black men as compared with white men and a higher incidence of squamous cell carcinoma in white women as compared with black women. The entity is rare before the age of 25 years, and most patients are seen clinically between the ages of 35 and 50 years. Histologic examination of tissue specimens has, for many decades, occupied the central role in the determination of malignancy, the classification of neoplasms, the grading of tumors, and (in most circumstances) the staging of disease. Wallace M L, Smoller B R 1997 Trichoepithelioma with an adjacent basal cell carcinoma, transformation or collision Tatnall F M, Wilson Jones E 1986 Giant solitary trichoepitheliomas located in the perianal area: a report of three cases. Similar to glial cells of other areas of the central nervous system, pituicytes extend cell processes to adjacent connective tissue or to a blood vessel wall. Thus the features of these lesions are closer immunohistochemically and ultrastructurally to those of meningeal arachnoid granulations than to true chemodectoma. Int J Dermatol 35: 881-883 Coskey R J, Mehregan A H, Hashimoto K 1982 Porokeratotic eccrine duct and hair follicle nevus. True primary neuroendocrine carcinomas of breast appear to have a worse prognosis than conventional ductal carcinoma. For a tumor to be confirmed as tubular it must exhibit a clearly tubular morphology in over 90% of the lesion. They also tend to occur in locations where nonossifying fibromas (see later discussion) are not normally found, such as the pelvic bones. The symptoms are nonspecific, and patients usually reports pain, perhaps of long duration. Roughly 70% of mesotheliomas will be predominantly epithelioid, 25% predominantly biphasic, and 5% predominantly sarcomatoid. Although some authors consider myoepithelium to be an integral component of this tumor type,321,384 myoepithelial cells are absent or at most present very focally at the lightmicroscopic level. Coffin C M, Lowichik A, Putnam A 2009 Lipoblastoma: a clinicopathologic and immunohistochemical analysis of 59 cases. However, in chondrosarcoma, the formation of trabecular-appearing bone from the cartilage is not evident. Evans H L, Soule E H, Winkelmann R K 1979 Atypical lipoma, atypical intramuscular lipoma and well differentiated retroperitoneal liposarcoma.

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Mitotic figures or apoptotic cells are uncommon, but in some cases they may exist above the basal layer, raising the question of carcinoma in situ. Most often they involve the dermis and subcutis and histologically consist of a multilobulated, poorly delimited myxoid mass composed of scattered, plump, spindle and stellate fibroblasts; numerous thin-walled vessels; and inflammatory cells, characteristically neutrophils that are unassociated with necrosis or ulceration. The apocrine hidrocystoma and cystadenoma spectrum of lesions498,499 ranges from fluid-filled cysts with simple apocrine linings to multilocular cysts that contain apocrine-lined papillary structures. The low-grade tumors generally follow a less aggressive course than those of intermediate or highgrade histology. Furthermore, with the description of apoeccrine glands as normal glandular structures that develop after puberty, the whole issue may be a moot point. Newman B H, Taxy J B, Laker H I 1984 Laryngeal cysts in adults: clinicopathologic study of 20 cases. Arch Pathol Lab Med 129: 1444-1450 Kim B, Park S H, Min H S 2004 Nasal chondromesenchymal hamartoma of infancy clinically mimicking meningoencephalocele. Intercalated duct adenoma-a discrete, rounded, partially to completely encapsulated nodule with well-defined contours. Oral Surg Oral Med Oral Pathol 76: 73-81 Heffner D K 1983 Problems in pediatric otorhinolaryngic pathology. Infundibular Cyst (Epidermoid Cyst) Infundibular cyst is the most common type of follicular cyst (approximately 80%). At times, it is difficult to subclassify an osteosarcoma on limited tissue obtained from a needle biopsy or a resected specimen that has been treated with neoadjuvant chemotherapy. The tendency, which was widespread in the late 1960s and early 1970s, to lump together schwannoma, neurofibroma, and solitary circumscribed neuroma without discrimination as "benign nerve sheath tumor" is to be discouraged, because it conceals significant clinicopathologic differences, particularly with regard to the risks of associated neurofibromatosis or of malignant change. One group754 has proposed that true mucoepidermoid tumors of the breast can be distinguished by the presence of a mixture of elements including mucinsecreting cells, squamous cells, intermediate cells, and myoepithelial cells. Ordonez N G 2006 Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases. These lesions do not occur in the skin, and lesions so described in the past would better be classified nowadays as storiform collagenoma (see later discussion). Ferreiro J A, Nascimento A G 1995 Hyaline-cell rich chondroid syringoma: a tumor mimicking malignancy. Note the lack of a capsule superficially and the nerve of origin in the bottom right corner. Intraoral examples, especially those arising from the palate, may lack a well-defined capsule. Primary lymphomas of bone demonstrate the same histologic features as their extraosseous counterparts and are classified by the same criteria. Papageorgiou S, Litt J Z, Pomeranz J R 1967 Multiple granular cell myoblastomas in children. Myocytes, in cardiac rhabdomyoma, 16 Myoepithelial carcinoma of breast, 1120-1121 of salivary glands, 296 Myoepithelial cells, in salivary glands, 271 Myoepithelial hamartoma, gastric, 420-421 Myoepithelial neoplasms, of breast, 1120-1125 Myoepithelial sialadenitis, 352-353 and lymphoepithelial carcinoma, 345 Myoepithelioma of breast, 1120-1121 of salivary glands, 293-296 soft tissue, 1844-1845 Myoepitheliosis, of breast, 1120 Myofibroblastic proliferations, reactive, at visceral locations, 1809-1810 Myofibroblastic sarcoma, low-grade, 1824 Myofibroblastic tumor, inflammatory. Two main morphologic subtypes are recog nized, the "pure" type in which the stellate nature is pronounced, with central yellow elastosis and radiating arms, and the sclerosing type, characterized by a more diffuse, illdefined appearance. It presents in neonates of either sex, most often after breech or forceps delivery, and is associated with neck asymmetry and tightness. Reconstructions of multiple levels through these lesions demonstrate the numerous perforating connections to the epidermis. Gross examination reveals a circumscribed mass with gray-white, whorled cut surface. Interestingly, these nodules show no meningeal covering, either morphologically or immunohistochemically228; this suggests that the notion that these lesions represent sequestrated encephaloceles may be too simplistic. Two other forms of well-differentiated liposarcoma are encountered more rarely: the inflammatory type,85,86 which is almost always retroperitoneal in location and in which numerous prominent lymphoplasmacytic aggregates may simulate inflammatory pseudotumor. Synonyms include large cell carcinoma, pleomorphic carcinoma, and anaplastic carcinoma. Brain Pathol 14: 281-289 Kalyan-Raman U P, Olivero W C 1987 Ganglioglioma: a correlative clinicopathological and radiological study of ten surgically treated cases with follow-up.

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Well characterized but very rare Malignant variants of Malignant variants have rarely other odontogenic been described for most epithelial tumors tumors. The tumor islands exhibit a cellular periphery and frequently necrotic or myxoid central zone. The individual glands are surrounded by an attenuated layer of myoepithelium, which may require immunostains for demonstration. Only when such lesions are multiple and clustered around the lower limb girdle should the term nevus lipomatosus superficialis be applied. The histopathologic features of osteosarcoma in the head and neck are comparable with those at other locations (see Chapter 25). These tumors were first described by Klemperer and Rabin287 as a form of localized fibrous mesothelioma. A special case occurs when melanoma in situ and dermal regression are observed in a lesion in which a biopsy has not been performed. Salivary Gland Anlage Tumor Clinical Features Salivary gland anlage tumor manifests in newborns or within first few weeks of life with respiratory distress. Fortunately, few, if any, intraocular processes can be confused with retinoblastoma histologically. Axelsen S M, Stamp I M 1995 Lymphoepithelioma-like carcinoma of the vulvar region. Barnes L M, Nordlund J J 1987 the natural history of dysplastic nevi: a case history illustrating their evolution. J Laryngol Otol 103: 756-759 Ellis G L, Wiscovitch J G 1990 Basal cell adenocarcinomas of the major salivary glands. Tang S K, Wan S K, Chan J K 1995 Hyalinizing clear cell carcinoma of salivary gland: report of a case with multiple recurrences over 12 years. This variation in pattern further emphasizes the need to sample tumors adequately. Enlarged, angular fibroblasts and occasional multinucleate fibroblasts are seen in some cases. Clinical Features Spindle cell and pleomorphic lipomas57-60 most often develop in mid-adult to late adult life and show a striking predilection for men. Islands of adipose tissue are found frequently, often in the center of the lesion. Squamous metaplasia may be seen focally or, if infected, may completely replace the respiratory epithelium; in the presence of infection, a chronic inflammatory cell infiltrate may be seen in the wall of the cyst. For eyes containing either retinoblastoma or melanoma, it is critical that the pathologist identify the location of the intraocular tumor before opening the eye. Laryngeal papillomas have traditionally been divided into juvenile and adult types, but the multiple recurring papillomas, whether presenting in childhood or adulthood, are now generally considered to represent the same basic entity,7,8 although childhood cases tend clinically to be more aggressive than those occurring initially in adults. A discussion of all of these techniques is outside the scope of this chapter, but a few brief points are mentioned. Shumack S P, Commens C A 1989 Disseminated superficial actinic porokeratosis: a clinical study. The presence of intracytoplasmic polymorphonuclear leucocytes or cellular debris would further buttress this diagnosis. Fisher E R, Sass R, Fisher B 1984 Pathologic findings from the National Surgical Adjuvant Project for Breast Cancers (protocol No 4). Kromann N, Hoyer H, Reymann F 1983 Chondrodermatitis nodularis chronica helicis treated with curettage and electrocauterization: follow-up of a 15-year material. These result from increased intralaryngeal pressure with relaxed supraglottic muscles against tightened lips, as in brass instrument players or glassblowers. Soft tissue perineurioma (known formerly as storiform perineurial fibroma) has only been recognized in more recent years to be a distinctive type of nerve sheath tumor.

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It is likely that some of these lesions begin as melanomas with pagetoid or lentiginous components that are overgrown by the nodular component. In this case, the histology technician should be asked to re-embed the specimen or cut deeper sections until the mucocutaneous junction can be visualized and evaluated. Differential Diagnosis Histologically the lesion may be identical to osteoblastoma, but the clear association with a tooth root allows the diagnosis. Melanomas composed predominantly of epithelioid cells are designated epithelioid melanomas. Fisher B, Dignam J, Wolmark N 1999 Tamoxifen in the treatment of intraductal breast cancer: national Surgical Adjuvant Breast and Bowel Project B24 randomised control trial. The nuclei are hyperchromatic and have a characteristically irregular membrane with an angular to ovoid shape. Radiographically, it may be difficult to separate these from synovial chondromatosis. Acral Myxoinflammatory Fibroblastic Sarcoma Acral myxoinflammatory fibroblastic sarcoma,348,349 also known as inflammatory myxohyaline tumor, occurs principally (but not exclusively) in the distal extremities, particularly the hands, of adults and presents as a slowly growing mass. Childers E L, Fanburg-Smith J C 2011 Congenital epulis of the newborn: 10 new cases of a rare oral tumor. A mononuclear infiltrate of lymphocytes, plasma cells, or both, is usually present. The soft tissue extension is usually limited by a shell of periosteal new bone formation. These lesions have architectural and cytologic features very similar to those of the more conventional pigmented spindle cell nevus and usually contain less melanin. It is a well-circumscribed lesion, usually less than 5 cm in diameter, composed of plump round, ovoid, or spindle-shaped cells set in a copious edematous matrix in which are numerous capillary-sized vessels. Those in which tumor is confined principally within nests in the epidermis are epidermal acrospiroma or hidroacanthoma. Focal necrosis may be present (seen in approxi mately 60% of cases), and this is occasionally extensive. These tumors are circumscribed and have a false capsule of compressed breast tissue, with only rare entrapped mammary parenchymal structures. Enchondromas grow by expansion and destruction of medullary bone and thus do not permeate between bony trabeculae. Approximately 50% of cases metastasize eventually, and the overall 5-year survival is 60% to 65%. Cytologic atypia is defined by the presence of a threefold variation in nuclear size and prominent nucleoli. Immunohistochemical stains can be helpful in making the distinction from carcinoma. Histologically, gangliogliomas are composed of a mixture of neoplastic ganglion cells and glial cells. Histologically, myxopapillary ependymomas are composed of papillary arrangements of elongated fibrillary cells that extend delicate processes to hyalinized vessels. The intercalated ducts are in continuity with the striated ducts, which have a wider lumen lined by columnar oncocytic cells. Radiographs shows a mineralized lesion that is attached to the distal phalanx of the toe but does not show continuity with it, as should be seen in a true osteochondroma. Considerable variation exists in the histologic appearances, depending in part on the interplay between the epithelial and stromal com ponents, and it is not possible to be prescriptive about the features used for its classification. Histologically, at low magnification, benign notochordal cell tumor fills the marrow spaces without destroying the medullary or cortical bone. B, Cytokeratin immunoreactivity is present and usually is focal but may be negative. Mitoses may number up to 10 per 10 hpf, and nuclear pleomorphism may also be seen; the latter is degenerative (pyknotic) in nature and is usually dissociated from the mitotic areas.

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B, Left panel, follicle lysis with attenuation and loss of mantle lymphocytes; right panel, clustering of multinucleated giant cells near surface (and/ or crypt) epithelium. Wheeler J E, Enterline H T 1976 Lobular carcinoma of the breast in situ and infiltrating. This subdivision is achieved by assessing histologic type and histologic grade, respectively. Schewach-Millet M, Trau H 1984 Congenital papillated apocrine cystadenoma: a mixed form of hidrocystoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Important to mention is the occurrence of basophilic invasion of the posterior lobe. The usually abundant vascular stroma forms a geometric network of delicate, thin-walled vessels, mimicking a "chicken-wire" pattern and segregating incomplete clusters of tumor cells. In some instances, however, a papillary growth pattern predominates, and the lesion qualifies for the designation of papillary carcinoma. B, the lining cells are stratified, including epidermoid cells and mucinous cells. Light microscopic, immuno histochemical and ultrastructural characteristics of two cases. They share the capacity for infiltrative, destructive, and commonly recurrent growth but have no capacity to metastasize. Smith B C, Ellis G L, Meis-Kindblom J M, Williams S B 1995 Ectomesenchymal chondromyxoid tumor of the anterior tongue. In the setting of keratinizing dysplasia where surface maturation is retained with only partial replacement of the epithelium by atypical cells, severe dysplasia includes those lesions in which the epithelial alterations are so severe that a high probability would exist for the progression to an invasive carcinoma if left untreated. Tricholemmoma Tricholemmoma359 is characterized by solitary or multiple papules composed histologically of glycogenated clear epithelial cells that are delimited by a prominent vitreous layer, similar to those of the outer sheath of the transient portion of the hair follicle, that is, principally that of the bulb region. From the histologic point of view, with very few exceptions these tumors are most often composed of an admixture of fibroblasts and myofibroblasts in varying proportions; these proportions may vary during the time course of the disease process. A mixed chronic inflammatory cell infiltrate composed of lymphocytes, plasma cells, and histiocytes may be prominent in the stroma. These tumors share the same immunohistochemical and molecular features, differing only in the extent of neural differentiation. Collagenoma, storiform, 1816 Collagenous fibroma, 1816 Collagenous neurofibroma, 2040-2041 Collecting duct carcinoma, 570-572 Collision tumor, 1232 Colloid adenocarcinoma, of bladder, 632-633 Colloid carcinoma of breast, 1095 of lung, 211 Colon cancer. The diagnosis of neoplasms of the eye and adnexa adds an additional dimension: the pathologist must provide information that also helps the surgeon to preserve vision, a therapeutic goal that may assume equal importance to the treatment of the neoplasm itself. Folberg R, McLean I W, Zimmerman L E 1985 Primary acquired melanosis of the conjunctiva. The nodule occasionally "pops" out of the surrounding tissue at the time of surgery or gross examination. Spindelzellenund/oder epitheloidzellennaevus: eine klinische analyse von 652 tumoren. The more solid component may be composed predominantly of clear cells embedded in a fibrous stroma. Published ratios for grades 1, 2, and 3 are approximately 2: 3: 5 in symptomatic breast cancer, so about half of all symptomatic cancers are grade 3. The histologic features strongly resemble those of synovial chondromatosis (see later). Patients range in age from the fifth to seventh decades (mean 54-56 years), with male predilection. Such tumors have been identified microscopically or grossly in autopsy cases reported in the literature. Acceptance is now general that the term mucinous carcinoma should only be applied to tumors in which at least 90% of the structure is of pure mucinous appearance. Sections taken from the junction between apparently normal bronchial mucosa and frank squamous cell carcinoma will often display changes that range from squamous metaplasia to intraepithelial atypia (dysplasia) to carcinoma in situ. Staining with p63 may vary from diffuse and strong to focal scattered moderately to strongly positive nuclei. Quizilbash A H, Patterson M C, Oliveria K F 1977 Adenoid cystic carcinoma of the breast. On the other hand, the patients may be completely asymptomatic when the tumors are peripherally located.

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More than 50% of patients eventually have metastases, most often to lymph nodes, lung, or bone, but this is commonly delayed over many years. It is more fully described in Chapter 13, but it is important to note that comparable lesions also occur rarely in the pelvic region of men. Additional immunohistochemical staining includes cytokeratins and may also include Leu 7, neurofilament protein, epithelial membrane antigen, and carcinoembryonic antigen. However, staging and grading of these tumors can provide valuable 1102 16 Tumors of the Breast prognostic information. Of patients with advanced-stage lung cancer, 10% to 20% had dramatic tumor regression; these tended to be women, neversmokers, of East Asian origin, with adenocarcinoma rather than squamous histology. Hagen P, Lyons G D, Haindel C 1993 Verrucous carcinoma of the larynx: role of human papillomavirus, radiation, and surgery. Adams J H, Graham D I, Doyle D 1981 Brain biopsy: the smear technique for neurosurgical biopsies. Herrold K M 1964 Induction of olfactory neuroepithelial tumors in Syrian hamsters by diethylnitrosamine. McCalmont T H 1996 A call for logic in the classification of adnexal neoplasms [editorial]. Sebaceous Neoplasms Sebaceous cells can normally occur in the parotid gland, submandibular gland, and oral minor salivary gland. Landman G, Taylor R M, Friedmen K J 1990 Cutaneous papillary squamous cell carcinoma. Bowen disease designates a clinical presentation of large erythematous plaque usually occurring on the trunk. Some surgeons do not remove the entire periosteum (which they may refer to as the periorbita) during an orbital exenteration, so absence of this anatomic landmark does not always indicate a breach of tumor through this important anatomic plane. Clever H W, Sahl W J 1991 Multiple eccrine hidrocystomas: a nonsurgical treatment [letter]. Emmenegger B A, Wechsler-Reya R J 2008 Stem cells and the origin and propagation of brain tumors. Smear preparations of oligodendroglioma are diagnostic with poorly cohesive cells in a delicately fibrillated matrix. Additionally, patients with any number of these lesions may develop malignant melanoma, although individuals with numerous lesions of any histologic type who have had melanoma or have a family history of melanoma are probably at higher risk. In certain settings, a florid but bland epithelial proliferation may occur as a result of fungal infection, such as candidiasis. These drugs have direct effect on the tumor cells, inducing atrophy of lactotrophs with resultant tumor shrinkage. If the lesion is being surgically excised, it is important for the pathologist to examine the gross specimen to determine if the surgeon has curetted the area in question. Hsi E D, Nickoloff B J 1996 Dermatofibroma and dermatofibrosarcoma protuberans: an immunohistochemical study reveals distinctive antigenic profiles. Cystadenocarcinoma Clinical Features Cystadenocarcinoma or papillary cystadenocarcinoma represents the malignant counterpart of cystadenoma. Smooth geometric spaces between cells or micro papillary formations with even cellular placement 3. Sarode V R, Truelson J, Zaidie M 2010 Dedifferentiated epithelialmyoepithelial carcinoma of the parotid gland with aberrant expression of prostate specific antigen: a case report. Radiography shows a heavily calcified mass attached to the underlying cortex by a broad base. The intraventricular tumors are usually soft and papillary, whereas more homogeneous granular lesions arise in the parenchyma. Numerous uniform small glands or acini are seen, often with a back-to-back growth pattern without intervening stroma.