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Part 2 book Atlas of anatomic pathology presentation of content: Neurogenic tumors, soft tissue tumors of the mediastinum, germ cell tumors, lymphoproliferative disorders. Invite you to consult Part 2 book Atlas of anatomic pathology presentation of content: Neurogenic tumors, soft tissue tumors of the mediastinum, germ cell tumors, lymphoproliferative disorders. Invite you to consult
4 Neurogenic Tumors Neurogenic tumors of the mediastinum are relatively rare and are most often encountered in the pediatric-age population They most commonly arise from structures in the posterior mediastinum, although they can originate from all three mediastinal compartments Neurogenic tumors are, in fact, the most common tumors of the posterior mediastinum in both children and adults Neurogenic tumors can be of neuroblastic origin or may arise from peripheral nerve sheath elements (Table 4.1) Table 4.1 Neurogenic tumors of the mediastinum Neuroblastic tumors Ganglioneuroma Ganglioneuroblastoma Neuroblastoma Peripheral nerve sheath tumors Schwannoma Neurofibroma Malignant peripheral nerve sheath tumor 4.1 Neuroblastic Neoplasms Neuroblastic neoplasms (Figs 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4.10, 4.11, 4.12, 4.13, 4.14, 4.15, 4.16, 4.17, 4.18, 4.19, 4.20, 4.21, 4.22, 4.23, 4.24, 4.25, 4.26, 4.27, 4.28, 4.29, 4.30, 4.31, and 4.32) arise from primitive precursor cells of the sympathetic nervous system They are the most common solid tumors in children under year of age, although they can also occur in older children and in adults Some cases can be associated with neurofibromatosis (NF1) They show a histologic spectrum that ranges from very welldifferentiated and mature neuronal elements to tumors composed of primitive and poorly differentiated cells, mimicking the entire spectrum of neuroblastic maturation Fig 4.1 Neuroblastic tumors are most often large and solid, well circumscribed, and surrounded by a fibrous capsule They usually show a smooth outer surface This image is an example of a ganglioneuroma, the most common benign tumor originating from the thoracic sympathetic nerves S Suster (ed.), Atlas of Mediastinal Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4939-2674-9_4, © Springer Science+Business Media, LLC 2015 89 90 Neurogenic Tumors Fig 4.2 Ganglioneuromas are benign neurogenic tumors composed of mature neural elements admixed in varying proportions They are often paucicellular and show a variously collagenized stroma on scanning magnification Fig 4.4 Schwannian stroma-poor ganglioneuroma shows a focus (center) containing large ganglion cells with abundant cytoplasm and round nuclei that are intimately admixed in various proportions with the spindle cells and collagenous stroma Fig 4.3 On higher magnification, ganglioneuromas are composed mainly of loose, fibrocollagenous stroma admixed with bland-appearing fibroblastic or schwannian spindle cells The stroma may vary from loose and edematous to densely collagenized Based on the extent of the schwannian component, they have been classified into schwannian stroma dominant (“mature” ganglioneuroma) and schwannian stroma poor (“maturing” ganglioneuroma) Fig 4.5 Higher magnification from the field in Fig 4.4 shows a cluster of large ganglion cells with abundant granular eosinophilic cytoplasm and large, round nuclei 4.1 Neuroblastic Neoplasms Fig 4.6 Schwannian stroma-rich mediastinal ganglioneuroma shows clusters of large ganglion cells with small, round nuclei surrounded by abundant granular eosinophilic cytoplasm embedded in a dense collagenous stroma containing abundant schwannian spindle cells Fig 4.7 Higher magnification of schwannian stroma-rich ganglioneuroma showing large ganglion cells with eccentric nuclei 91 Fig 4.8 Higher magnification of ganglion cells in ganglioneuroma showing characteristic small nuclei surrounded by abundant pink granular cytoplasm The number of ganglion cells in these tumors may vary; if they are very sparse, proper identification may require a diligent search Fig 4.9 Ganglioneuroblastoma is a tumor characterized by an admixture in various proportions of both mature schwannian and ganglionic elements, as well as primitive neuroblastic elements that form discrete nests or islands of tumor cells The tumors are grossly well circumscribed, with a fleshy, tan-white cut surface with focal areas of cystic degeneration and foci of calcification 92 Fig 4.10 Histologically, ganglioneuroblastoma shows areas that are indistinguishable from ganglioneuroma in association with foci of neuroblastic elements The neuroblastic elements are arranged in discrete, small nests of primitive neuroblastic cells (lower right) that merge with the schwannian-rich stroma (left) Fig 4.11 Higher magnification from the field in Fig 4.10 shows bland-appearing schwannian spindle cells (left) percolating between small nests of small neuroblastic cells (right) Neurogenic Tumors Fig 4.12 Schwannian stroma-poor ganglioneuroblastoma shows a paucicellular, collagenous stroma merging imperceptibly with islands and nests of primitive, small neuroblastic cells admixed with larger ganglionic cells Fig 4.13 Higher magnification of schwannian stroma-poor ganglioneuroblastoma shows a mixed cell population composed of small, primitive neuroblastic cells admixed with larger ganglionic cells 4.1 Neuroblastic Neoplasms Fig 4.14 Another example of ganglioneuroblastoma shows a few small nests containing neuroblastic elements surrounded by a schwannian-rich spindle-cell stroma Fig 4.15 Higher magnification of ganglioneuroblastoma showing a mixed population of neuroblastic small cells admixed with larger ganglionic cells with abundant eosinophilic cytoplasm 93 Fig 4.16 Ganglioneuroblastoma with foci of dystrophic calcifications Neuroblastoma elements occasionally undergo dystrophic calcification that replaces the tumor cells The presence of these foci of calcification is an indication of a neuroblastic component in the tumor and should prompt search of additional sections Fig 4.17 Neuroblastoma is the most common malignant neoplasm of the posterior mediastinum in children, particularly under the age of year Grossly, the tumors are well circumscribed and encapsulated, with a multinodular outer surface 94 Fig 4.18 Cut surface of a neuroblastoma shows grayish white, soft tissue with areas of hemorrhage and necrosis and foci of calcification Fig 4.19 Histologically, neuroblastoma is composed of a proliferation of small, round blue cells showing various degrees of organization Neuroblastomas have been classified into differentiating, poorly differentiated, and undifferentiated, depending on their degree of maturation and organization The well-differentiated tumors (differentiating neuroblastoma) overlap with ganglioneuroblastoma but show a predominance of neuroblastic elements over ganglionic cells and may also contain a minor schwannian component The poorly differentiated variants show no evidence of ganglionic or schwannian differentiation and grow as sheets of small tumor cells that often present a nested appearance, as in this example Neurogenic Tumors Fig 4.20 Higher magnification from Fig 4.19 shows well-defined islands or nests of tumor cells separated by a vascular stroma Fig 4.21 Higher magnification showing well-defined nests of tumor cells with abundant fibrillary eosinophilic material (neuropil) in the background The fibrillary material (neuropil) is a distinctive feature of neuroblastic neoplasms and helps in the differential diagnosis with other small, round cell tumors 4.1 Neuroblastic Neoplasms 95 Fig 4.22 Another area in the same tumor shows a peculiar linear, single-file arrangement of neuroblastic cells embedded in abundant fibrillary matrix, a feature often observed in these tumors Fig 4.24 Higher magnification in calcifying neuroblastoma shows irregular deposits of calcific material surrounded by proliferation of primitive, small, round blue cells Fig 4.23 Extensive stromal calcification is a common feature in neuroblastoma The calcifying process can be so extensive as to obscure the underlying neoplastic proliferation; recognition of the tumor cells may then require extensive sampling Fig 4.25 Higher magnification shows small nests of tumor cells admixed with calcific stromal deposits The tumor cells show a primitive appearance with small, round nuclei with tiny nucleoli and no discernible cytoplasm 96 Neurogenic Tumors Fig 4.26 Another example of differentiating neuroblastoma on scanning magnification shows a lobular growth pattern separated by wellvascularized stroma and foci of stromal calcifications Fig 4.28 High power shows a scant amount of tumor cells displaying various degrees of maturation, floating in abundant eosinophilic fibrillary matrix (neuropil) Fig 4.27 Higher magnification shows a lobule of tumor cells with abundant background neuropil and a mixed cell population, including ganglionic-type large cells and scattered smaller neuroblastic cells Fig 4.29 This neuroblastoma of an “undifferentiated” type shows almost solid sheets of small, round, primitive cells with only a vague hint of nesting 4.1 Neuroblastic Neoplasms Fig 4.30 Higher magnification from the same case as Fig 4.29 shows a primitive population of small, round, blue cells growing as sheets with scattered mitoses The tumor cells have small, irregular nuclei with scant nuclear detail and small nucleoli Fig 4.31 Higher magnification shows the presence of Flexner-type rosettes, another distinctive feature sometimes seen in poorly differentiated neuroblastoma 97 Fig 4.32 Immunohistochemistry can aid in the differential diagnosis of neuroblastoma, particularly the poorly differentiated and undifferentiated forms Neuron-specific enolase (pictured) and other neuronal markers (synaptophysin, chromogranin, neurofilament protein, etc.) are generally positive in the tumor cells, to the exclusion of other specific markers of differentiation (keratins, desmin, actin, S-100 protein, etc.) Molecular genetics also plays a role, as alterations such as overexpression of MYCN and chromosome 1p deletion have been associated with more aggressive behavior and can serve as markers for the more poorly differentiated tumors 98 4.2 Peripheral Nerve Sheath Tumors Peripheral nerve sheath tumors (PNSTs) are the most commonly encountered tumors in the posterior mediastinum These can also show a wide spectrum of differentiation ranging from benign, fully differentiated neural tumors (schwannoma, Figs 4.33, 4.34, 4.35, 4.36, 4.37, 4.38, 4.39, 4.40, 4.41, 4.42, 4.43, 4.44, 4.45, 4.46, 4.47, 4.48, 4.49, 4.50, 4.51, Fig 4.33 Schwannoma is the most common type of peripheral nerve sheath tumor (PNST) of the mediastinum Although nearly all are seen in the posterior mediastinum, they can also present as anterior mediastinal masses Grossly, the tumors are encapsulated and well circumscribed The cut surface is characterized by tan, homogenous, somewhat lobulated tissue with areas of cystic degeneration Fig 4.34 Schwannomas are characterized by bland-appearing spindle-cell proliferation that is completely surrounded by a fibrous capsule Neurogenic Tumors 4.52, 4.53, 4.54, 4.55, 4.56, 4.57, 4.58, and 4.59) to tumors showing a prominent fibroblastic component (neurofibroma, Figs 4.60, 4.61, 4.62, and 4.63) to poorly differentiated malignant neural neoplasms (malignant PNSTs, Figs 4.64, 4.65, 4.66, 4.67, 4.68, 4.69, 4.70, 4.71, 4.72, 4.73, 4.74, 4.75, and 4.76) The tumors most often affect young to middleaged adults and are commonly seen in a paravertebral location Some tumors may adopt a dumbbell configuration and penetrate into the spinal canal Fig 4.35 The spindle cells in schwannoma form fascicles that can intersect at right angles Two growth patterns are recognized: (1) Antoni type A (illustrated), characterized by closely packed tumor cells, and (2) Antoni type B, characterized by loosely arranged spindle cells separated by abundant myxoid or edematous stroma Fig 4.36 Higher magnification from Antoni type A area of schwannoma shows tightly packed spindle cells forming fascicles that appear to cross at right angles 7.3 Hodgkin Lymphoma 211 Fig 7.93 Immunohistochemical staining with CD15 antigen also shows strong positivity of the HRS cells in nodular sclerosing Hodgkin lymphoma; some of the cells also show a paranuclear dot-like pattern of staining with this antibody A positive-staining binucleated ReedSternberg cell is also seen (center) Fig 7.95 At higher magnification, this example of the syncytial variant of Hodgkin lymphoma of the mediastinum shows sheets of large mononuclear and binucleated lacunar cells with no significant intervening inflammatory component Fig 7.94 Rarely, nodular sclerosis Hodgkin lymphoma of the mediastinum will show prominent cellular aggregates of lacunar cells surrounding areas of necrosis; such cases are referred to as the “syncytial” variant of Hodgkin lymphoma Fig 7.96 Immunohistochemical staining for CD30 antigen shows sheets of large CD30+ cells concentrated around areas of necrosis in the syncytial variant of mediastinal Hodgkin lymphoma 212 Lymphoproliferative Disorders Fig 7.97 A frequent finding in mediastinal Hodgkin lymphoma is secondary cystic changes of the thymic epithelium The cysts may be quite prominent and can overshadow the lymphoid cell population, leading to the formation of a multilocular cystic mass that can be mistaken for a benign multilocular thymic cyst on cursory examination Fig 7.99 This more advanced example of stromal fibrosis in the nodular sclerosis subtype of Hodgkin lymphoma shows small residual lymphoid nodules separated by extensive areas of collagenized stroma Careful attention to the cell composition in the residual nodules is required for correct diagnosis Fig 7.98 Careful examination of the wall of the cysts will disclose solid areas with a dense lymphoid cell population containing scattered HRS cells Extensive sampling is always indicated in cystic tumors of the mediastinum, to rule out Hodgkin lymphoma Fig 7.100 At higher magnification, the solid lymphoid nodule in Fig 7.99 shows small lymphocytes surrounded by dense collagen and containing a few scattered mononuclear Hodgkin cells with prominent eosinophilic nucleoli 7.3 Hodgkin Lymphoma 213 Fig 7.101 Another example of nodular sclerosis Hodgkin lymphoma of the mediastinum with quite advanced stromal sclerosis shows only residual small clusters of small lymphocytes A careful search for HRS cells is mandatory; the use of stains for CD30 and CD15 may be helpful in identifying residual atypical cells Fig 7.103 Some cases of Hodgkin lymphoma of the mediastinum may contain an abundant histiocytic component that will give the lesion a granulomatous appearance The histiocytes grow as sheets and contain scattered HRS cells In the past, similar cases were designated as “Lennert’s lymphoma.” Such cases are more common in immunocompromised and HIV-positive patients Fig 7.102 Mediastinal nodular sclerosis Hodgkin lymphoma may also contain entrapped hyperplastic thymic epithelium, particularly at the edges of the tumor This epithelium will stain with cytokeratin antibodies and p63; it should not be mistaken for thymoma Fig 7.104 At higher magnification, the example in Fig 7.103 shows a multinucleated Reed-Sternberg cell in the middle of the field, displaying prominent eosinophilic nucleoli 214 Lymphoproliferative Disorders Fig 7.105 Mixed-cellularity Hodgkin lymphoma is characterized by a diffuse lymphoid infiltrate that contains abundant scattered HRS cells Mediastinal involvement by this subtype of Hodgkin lymphoma is rare Fig 7.107 Hodgkin lymphoma of the lymphocyte-depletion subtype is extremely rare in the mediastinum and can be easily mistaken for anaplastic large cell lymphoma The tumor grows as sheets of large lymphoid cells containing a very sparse, small lymphoid cell population Fig 7.106 At higher magnification, the mixed-cellularity subtype of Hodgkin lymphoma shows numerous, scattered mononuclear and binucleated HRS cells against a background of mixed inflammatory cell infiltrate Fig 7.108 At higher magnification, mediastinal lymphocyte-depleted Hodgkin lymphoma closely resembles anaplastic large cell lymphoma, including kidney-shaped HRS cells that are virtually indistinguishable from the “hallmark” cells of that disorder Because both stain for CD30, the use of additional antibodies such as PAX5 (positive in Hodgkin lymphoma) and ALK1 (positive in anaplastic large cell lymphoma) is recommended 7.4 MALT Lymphoma (Marginal Zone Lymphoma of the Thymus) 215 7.4 Fig 7.109 Mediastinal lymphocyte-depleted Hodgkin lymphoma also can adopt a spindled appearance with a well-developed storiform pattern that resembles a spindle-cell sarcoma Such cases were incorrectly interpreted in the past as examples of transformation of Hodgkin lymphoma into malignant fibrous histiocytoma Use of special stains for CD30 and ample sampling to identify more conventional areas of Hodgkin lymphoma are indicated in such instances MALT Lymphoma (Marginal Zone Lymphoma of the Thymus) Mucosa-associated lymphoid tissue (MALT) lymphoma of the mediastinum is a relatively rare low-grade malignancy derived from a distinctive native population of thymic postgerminal center-stage parafollicular B cells Some have postulated that it may represent a precursor lesion to diffuse large B-cell lymphoma of the mediastinum Because lymphoid hyperplasia is a prominent component of the lesion, in the past most cases were erroneously diagnosed as florid lymphoid hyperplasia or “pseudolymphoma.” MALT lymphoma is usually asymptomatic and is discovered incidentally on routine chest X-rays The lesions are often associated with cystic degeneration and may present as multilocular cystic lesions on imaging studies The tumors have an indolent growth with a protracted clinical course and are associated with an excellent prognosis Some cases have been associated with Sjögren’s syndrome and polyclonal hypergammaglobulinemia MALT lymphoma is positive for CD11c, CD20, CD24, CD43, bcl-2, and IgA It is negative for CD5, CD10, CD21, CD23, CD25, CD35, and cyclin-D1 Diagnosis may be difficult to make with immunohistochemistry and requires identification of the characteristic histologic features associated with these tumors (Figs 7.110, 7.111, 7.112, 7.113, 7.114, and 7.115) Recognition of the sheets of monotonous, small lymphocytes in the interfollicular spaces is helpful for making this diagnosis Fig 7.110 Grossly, MALT lymphoma of the thymus is characterized by diffuse enlargement of the thymus with secondary cystic changes The tumors are not invasive and are contained within the capsule of the organ 216 Lymphoproliferative Disorders Fig 7.111 Histologically, MALT lymphoma of the thymus shows prominent lymphoid follicular hyperplasia with sheets of monotonous, small lymphocytes distending the interfollicular spaces The interfollicular small lymphocytes may appear as normal small lymphocytes with minimal nuclear irregularities (similar to those of chronic lymphocytic leukemia), may be plasmacytoid, or may display a “monocytoid” appearance Fig 7.113 Another example of mediastinal MALT lymphoma, showing the monotonous population of small lymphocytes with plasmacytoid appearance The cells display a cartwheel chromatin pattern and ample eosinophilic cytoplasm, indicating plasmacytic differentiation Fig 7.112 At higher magnification, mediastinal MALT lymphoma shows a monotonous population of small lymphocytes with a rim of clear cytoplasm surrounding the nuclei, giving them a “monocytoid” appearance Fig 7.114 Another characteristic feature of MALT lymphoma of the thymus is that the neoplastic, monocytoid cells tend to surround and infiltrate Hassall’s corpuscles and residual thymic epithelium, forming distinctive lymphoepithelial lesions Suggested Reading 217 Suggested Reading Fig 7.115 Cystic dilatation of the underlying thymic epithelium is a common feature of mediastinal MALT lymphoma The lymphoid cells infiltrate the epithelial lining, and the residual thymic epithelium may be recognizable only by means of special stains, such as cytokeratins Allemani C, Sant M, De Angelis R, Marcos-Gragera R, Coebergh JW, EUROCARE Working Group Hodgkin disease survival in Europe and the U.S.: prognostic significance of 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Index A Acellular collagen atypical lymphoid cells, 185, 193 DLBCL, 185, 190 fibrosing process, 185, 193 Adipose tissue tumors See Liposarcoma Alpha-fetoprotein (AFP), 157, 173, 179 Alveolar rhabdomyosarcoma, 185, 196 Alveolar soft part sarcoma, 153 Anaplastic large cell lymphoma CD30 antigen, 185, 201 DLBCL, 185, 200 Hodgkin lymphoma, 207, 214 Angiosarcoma atypical spindle cells, 112, 122 epithelioid cells, 112, 121 hemorrhagic masses, 112, 121 spindle-cell morphology, 112, 122 vascular channels, 112, 121 Atypical carcinoid, 57 Atypical thymoma abundant cytoplasm, 41 chromatin pattern, 43 cytologic atypia, 44 eosinophilic cytoplasm, 42 malignant progression, 41 nuclear pleomorphism, 42 pleural and lungs, 44 raisinoid appearance, 43 recurrences, 45 squamous cell carcinoma, 42 squamous epithelium, 41 thymic carcinoma, 41, 44 B Basaloid carcinoma, 52 B-cell hyperplasia, 30 Bone and cartilage tumors See also Mesenchymal chondrosarcoma cartilaginous tumors, 146, 147 extraskeletal chondrosarcoma, 146 histologic appearance, 146 C Carcinoid tumor, 57 Carney, J.A., 98, 104 Castleman’s disease dysplastic germinal center, 14 epithelioid endothelial cells, 16 hyaline-vascular type, 14 hyalinized germinal centers, 16 hypervascularity, 15 interfollicular sclerosis and hyalinization, 16 lollipop sign, 15, 16 mediastinal lymph node, 14 plasma cell type, 16, 17 plump endothelial cells, 15 sclerosis and perivascular hyalinization, 15 striking lymphoid hyperplasia, 14 stromal hyalinization and concentric onionskin layer, 15 Chondrosarcoma See Mesenchymal chondrosarcoma Chordoma appearance, 146, 149 “bubbly” cytoplasm, 146, 149 characterization, 146, 148 hyperchromatic nuclei, 146, 149 trabecular pattern, 146, 148 Choriocarcinoma cytotrophoblastic cells, 165, 182 gonadal primary tumor, 165, 182 β-HCG, 165, 182 syncytiotrophoblastic cells, 165, 182 trophoblastic cells, 165, 182 Congenital and acquired thymic cysts cholesterol cleft granulomas, cuboidal epithelium, 2, epithelial cells, fibrous tissue, hemorrhage and cholesterol granulomas, inflammatory processes, lymphoepithelial type, lymphoid aggregates, infiltrates, MALT lymphoma, pseudoepitheliomatous hyperplasia, residual thymic epithelium, spindle cells, thymus, 1, Cushing’s syndrome, 57 Cystic lumina, 25 Cystic lymphangioma appearance, 112 composition, 112 lymph flow, 112 D Dermatofibrosarcoma protuberans, 21 Developmental cysts, 1, S Suster (ed.), Atlas of Mediastinal Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4939-2674-9, © Springer Science+Business Media, LLC 2015 219 220 Diffuse large B-cell lymphoma (DLBCL) abundant collagenous stroma, 185, 186 amphophilic cytoplasm, 185, 191 angiotropism, 185, 201 CD20, 185, 197 CD30 antigen, 185, 200 cellular clusters, 185, 187 chromatin and nucleoli, 185, 189 clear cell, 185, 194 cyst wall, 185, 199 cytokeratin, 185, 200 discohesive tumor cells, 185, 187 eosinophilic cytoplasm, 185, 194 fibrosis, 185, 188 hyperchromatic nuclei, 185, 189, 192 immunoglobulins, 185 immunohistochemical stains, 185, 189, 193 leukocyte antigen, 185, 202 lymphoid follicles, 185, 195 mediastinal lymphomas, 185, 194 medullary epithelium, 185, 199 pleura and pericardium, 185, 186, 190 signet-ring cells, 185, 198 stromal sclerosis, 185, 188 T-cell-rich mediastinal, 185, 193 Dystrophic calcifications, 61, 89, 93 E Eaton-Lambert syndrome, 57 Ectopic thyroid/parathyroid adenoma acinar architecture, 12 lymph nodes, 12 spindle cells, 13 tumor growths, Embryonal carcinoma apoptotic activity, 165, 181 CD30, 165, 181 germ cell tumors, 165, 172, 181 glandular architecture, 165, 180 nonteratomatous lesions, 165, 180 OCT4, 165, 168 papillary structures, 165, 180 Reed-Sternberg cells, 165, 181 seminoma, 165, 180 Eosinophilic cytoplasm (abundant), 30 Epithelioid hemangioendothelioma (mediastinal) characteristics, 112, 114 eosinophilic cytoplasm, 112, 118 epithelioid cells, 112, 114 factor VIII-related antigen, 112, 120–121 focal hemorrhage, 112, 116 growth patterns and cytologic appearance, 112, 114 immunohistochemical markers, 112, 120 intravascular growth, 112, 119 proliferation, 112, 113 pseudoinfiltrative growth pattern, 112, 117 retiform growth pattern, 112, 119 spindle-cell growth pattern, 112, 118 spindling, 112, 118 vascular neoplasm, 112, 113 vessel-like growth pattern, 112, 120 Epithelioid malignant schwannomas, 98, 108 Epithelioid thymoma Index B-type, 33 eosinophilic cytoplasm, 34 Hassall’s corpuscle, 36 lobulation, 34 lymphoblastic lymphoma, 35 macroscopic appearance, 33 medullary differentiation, 34 organoid/cortical, 35 pan-cytokeratin, 35 WHO, 33 Epstein-Barr virus (EBV), 185, 195, 207 Extraskeletal myxoid chondrosarcoma histogenesis, 146, 147 immunohistochemical stains, 146, 147 F Fibroblastic and fibrohistiocytic tumors SFTs (see Solitary fibrous tumors (SFTs)) storiform/cartwheel pattern, 123, 133 undifferentiated sarcoma, 132 Fibrocollagenous matrix, 24 Fibrosarcoma diagnosis, 131 and SFT, 123 Fibrous tissues alveolar pattern, 185, 196 nests, tumor cells, 185, 190 round cell infiltration, 185, 191 tumor islands, 185, 190 Fibrovascular stroma, 28 Foregut cyst blunt dissection, ciliated epithelium, 3, enteric type, squamous epithelium, G Ganglioneuroblastoma collagenous stroma, 89, 92 dystrophic calcifications, 89, 93 eosinophilic cytoplasm, 89, 93 neuroblastic elements, 89, 92 schwannian and ganglionic elements, 89, 91 Ganglioneuromas abundant cytoplasm, 89, 90 calcification, 89, 91 eosinophilic cytoplasm, 89–91 fibroblastic/schwannian stroma, 89, 90 mixed cell population, 89, 92 neuroblastic elements, 89, 92 small nests, 89, 93 small nuclei, 89, 91 Germ cell tumors additional malignant component, 158, 161–164 AFP, 157 classification, 157 HCG, 157 hematologic disorders, 157 mediastinum, 157 nonteratomatous (See Nonteratomatous lesions) serology, 157 teratomas (See Teratomatous lesions) Germinotropic lymphoma, 185, 195 Index H Hemangioma dilated vessels, 112 hamartomatous malformations, 113 mesenchymal tumors, 111 thin-walled vessels, 113 Hemangiopericytoma, 27 Histogenesis alveolar soft part, 150, 153 rhabdoid tumor, 150 synovial sarcomas, 150–151 Hodgkin lymphoma B-cell markers, 207 CD15 antigen, 207, 211 CD30 antigen, 207, 211 collagenized stroma, 207, 209 cysts, 207, 212 cytokeratin stains, 207, 213 diffuse lymphoid, 207, 214 EBV, 207 eosinophilic nucleoli, 185, 202, 207, 209, 212 fibrous tissue, 207, 208 immunohistochemical staining, 207, 210 inflammatory cell infiltration, 207, 214 lacunar cells, 207, 209, 211 Lennert’s lymphoma, 207, 213 lymphoid neoplasm, 207 nodular sclerosis, 207, 208 paranuclear staining, 207, 210 Reed-Sternberg cell, 207, 210 spindle-cell sarcoma, 207, 215 stromal fibrosis, 207, 212, 213 thymic epithelium, 207, 212 Human chorionic gonadotropin (HCG), 157 Hyperplastic lymphoid follicles, 185, 196 Hyperplastic thymic epithelium, 185, 199, 200 I Immature teratoma neural tubules, 158, 160 neuroepithelium, 158, 160, 161 seminomatous component, 158, 162 Immunoblastic lymphoma, 185, 194 Immunohistochemistry, thymomas CD1a staining, 47 hematoxylin and eosin, 46 immunostaining patterns, 46 keratin staining, 46 Ki-67 proliferation, 47 p63 testing, 46 Inflammatory liposarcoma, 185, 198 Intranuclear inclusions, 98, 103 K Klinefelter’s syndrome, 157 Koga, K., 39 L Large cell neuroendocrine carcinoma cytoplasm, 83 diagnosis, 83 neoplasm, 82 221 peripheral palisading of nuclei, 82 Leiomyosarcomas bizarre nuclei, 135, 136 epithelioid characterization, 135, 136 eosinophilic cytoplasm, 135, 137 fascicular architecture, 135 homogeneous tan-white cut surface, 135 markers, 135 nuclear atypia and pleomorphism, 135, 136 nuclear pleomorphism, 135 SMMS, 135, 136 Lipomatous tumors (atypical) characterization, 140 scattered atypical lipoblasts, 140, 141 Liposarcoma atypical lipoblast, 140, 141 diagnosis, 140, 144 FISH assay, 140, 143 heterologous elements, 140, 143 “inflammatory” type, 140, 142 lymphoid aggregates, 140, 141 MDM2 antibodies, 140, 144 myxoid stroma, 140, 143 sclerosis, 140, 141 spindle-cell component, 140, 144 thymoliposarcoma, 140, 142 Liver metastasis, 31 Lymphoblastic lymphoma cytokeratin stains, 206 Hodgkin lymphoma, 206 immature T-cell phenotype, 205 immunophenotype, 205 nuclear chromatin, 204 PNET, 206 T-cell lineage, 203 TCR genes, 203 thymomas, 203 tingible-body macrophages, 204 vascular markings, 203 Lymphocytes cytoplasm and chromatin, 32 epithelial cells, 33 epithelioid thymoma, 33–36 thymoma, 32 WHO, 32 Lymphoepithelioma-carcinoma, 50 Lymphoid follicular hyperplasia myasthenia gravis, 7, thymus, Lymphoid malignancy, 185, 186 Lymphoplasmacellular stroma, 50 Lymphoproliferative disorders B-cell lymphomas, 185 DLBCL (see Diffuse large B-cell lymphoma (DLBCL)) Hodgkin lymphoma, 207–215 lymphoblastic lymphoma, 203–207 lymphoid follicle, 185, 196 M Malignant fibrous histiocytoma (MFH) anaplastic tumor cells, 123, 133 pleomorphic sarcomas, 135 222 Malignant fibrous histiocytoma (MFH) (Cont.) undifferentiated sarcoma differentiation markers, 123, 134 epithelioid morphology, 123, 133 giant tumor cells, 123, 134 myxoid stroma, 123, 134 osteoclastic giant cells, 123, 133 “wastebasket” category, 123, 132 Malignant lymphoma, 185 Malignant peripheral nerve sheath tumor chromatin pattern, 98, 106 herringbone pattern, 98, 106, 107 necrosis, 98, 107, 108 neural neoplasms, 98 Malignant rhabdoid tumor, 150 Malignant schwannoma, 103, 105, 108 Marginal zone lymphoma, 215–217 Masaoka, A., 39 Mature teratoma dermoid cyst, 158, 159 exocrine and endocrine pancreatic tissue, 158, 159 keratinous debris, 158, 159 mature glial tissue, 158, 159 mucinous/serosanguinous fluid, 158 Mediastinal hemangiomas cavernous type, 112 hamartomatous malformations, 112, 113 in mediastinal location, 112, 115 Mediastinal thyroid goiter hyperplastic nodule, 12 scanning magnification, 11 thyroiditis and malignant transformation, 11 Mediastinitis acute and chronic inflammation, 1, 10 entrapment of large nerve trunks, 11 fibrous connective tissue, 10 inflammatory cells, 10 solitary fibrous tumor, 11 MEN See Multiple endocrine neoplasia (MEN) Mesenchymal chondrosarcoma cartilaginous matrix (immature), 146, 147 characterization, 146 hemangiopericytic growth, 146, 147 malignant neoplasm, 146 stromal collagenization, 146, 147 Mesenchymal neoplasm, 185, 198 Mesothelial (pericardial) cyst autopsy, polygonal mesothelial cells, MFH See Malignant fibrous histiocytoma (MFH) Microcystic thymoma, 25 Micronodular thymoma hyperplastic lymphoid follicles, 31 lymphoma, 31 Mixed lymphoepithelial thymoma B type thymomas, 37 cystic degeneration, 39 eosinophilic nucleoli, 37 invasion and metastases, 39 lobulation, 37 lungs lymph nodes, 39 lymphocytes, 36 multilocular thymic cyst, 38 necrosis and infarction, 38 Index neoplastic thymic epithelium, 38 perivascular spaces, 37 pleura infiltration, 39 thymic epithelial cells, 36 Monophasic synovial sarcomas, 27 Moran, C.A., 19 Mucinous adenocarcinoma, 53 Mucoepidermoid carcinoma, 49 Mucosa-associated lymphoid tissue (MALT) lymphoma cystic dilatation, 215, 217 lymphoepithelial lesions, 215, 216 lymphoid follicular hyperplasia, 215, 216 lymphoid hyperplasia, 215 monocytoid cells, 215, 216 multilocular cystic lesions, 215 pseudolymphoma, 215 thymus, 215 Multiple endocrine neoplasia (MEN), 57 Myasthenia gravis, 19 Myogenic differentiation, 185, 197 Myxoid chondrosarcoma, 147–149 Myxoid liposarcoma, 144–145 N Neuroblastoma benign tumor, 89 calcification, 89, 95 differentiated tumors, 89, 94 eosinophilic fibrillary matrix, 89, 96 fibrillary material, 89, 94 fibrous capsule, 89 Flexner-type rosettes, 89, 97 ganglioneuromas, 89, 90 hemorrhage and necrosis, 89, 94 immunohistochemistry, 89, 97 molecular genetics, 89, 97 nests, tumor cells, 89, 95, 96 neurofibromatosis, 89 posterior mediastinum, 89, 93 schwannian spindle cells, 89, 92 stromal calcifications, 89, 95, 96 vascular stroma, 89, 94 Neuroectodermal neoplasms, 22 Neuroendocrine carcinomas amyloid-like stromal deposits, 69, 77 biologic behavior, 57 bland-appearing spindle cells, 77 characterization, 78 cholesterol-cleft granulomas, 61 chromogranin-A, 67 classification, 57 collagenous stroma, 71 comedonecrosis, 60, 61 cribriform pattern, 79 cytoplasmic clearing, 79 desmoplasia, 71 diagnosis and infiltrate, 61 diffuse pattern, 72, 73 dystrophic calcification, 61 edematous stroma, 68 eosinophilic cytoplasm, 58, 59, 73, 77 fibrovascular septa, 75 fused glands appearance, 80 Index growth patterns and cytologic variants, 58, 60 histologic diagnosis, 57, 58 hyalinized stroma, 68 hyaluronidase, 69 immunohistochemical staining, 77, 80 lymphocytes, 72 massive stromal edema, 68 medullary thyroid, 69 melanoma, 28 MEN I and II syndromes, 57 mesenchymal neoplasm, 67 metastasis, 67 microacinar pattern, 80 monotonous tumor cells, 58, 59, 63, 82 morphologic spectrum, 57 nesting pattern, 28 nuclear chromatin, 7, 76 nuclear morphology, 28 oncocytic variant, 78 organoid, 58–60, 72 paraneoplastic syndromes, 57 perineurial invasion, 81 perivascular rosette, 73, 74 pleomorphism/mitotic activity, 63 pseudoangiomatous variant, 70, 71 pseudoglandular growth pattern, 66 red blood cells, 65 retraction artifact, 61 ribbon-like pattern, 64 rosette-like arrangement, 81 round cell morphology, 75 round to oval nuclei, 58, 59, 66 scattered epithelial cells, 69 serpiginous growth pattern, 65 small tumor cells, 64 spindle cells, 74, 75 stromal vessels, 73 synaptophysin and chromogranin, 66, 68 thymic tissue, 62 trabecular apoptotic tumor cells, 65 chromogranin, 64 cytokeratin AE1/AE3, 64 monotonous, 65 parallel cords, 66 “tzellballen” pattern, 76 vascular endothelium, 70 Neurofibromas interstitium, 98, 105 malignant transformation, 98, 104 multinodular lesions, 98, 104 Schwann cells, 98, 105 Neurogenic tumors neuroblastoma, 89–97 PNSTs (see Peripheral nerve sheath tumors (PNSTs)) posterior mediastinum, 89 Nonteratomatous lesions choriocarcinoma, 165, 182 embryonal carcinoma, 165, 180–181 seminoma, 165–172 yolk sac tumor, 165, 172–180 Nuclear cytomorphology, 203, 205 Nuclear pleomorphism, 185, 201 223 O Osteosarcoma, 111, 146, 164 P Papillary thymic carcinoma, 23 Paragangliomas circumscription and encapsulation, 84 endocrine atypia, 85 eosinophilic cytoplasm, 85 focal phenomenon, 85 histologic hallmark, 85 neuroendocrine markers, 86 stromal hemorrhage, 84 stromal sclerosis and angiectatic vessels, 86 Peripheral nerve sheath tumors (PNSTs) cystic degeneration, 98, 105 epithelioid malignant, 98, 108 fibrinous eosinophilic material, 98, 101 fibroblastic component, 98 herringbone pattern, 98, 107 monophasic synovial sarcoma, 98, 107 multinodular lesions, 98, 104 myxoid stroma, 98, 100 necrosis, 98, 105, 107 neurofibromas, 98, 104 neurogenic sarcoma, 98, 105 nuclear pleomorphism, 98, 106, 107 paravertebral location, 98 schwannoma, 98 spindle tumor cells, 98, 107 S-100 protein, 98, 106 stromal calcifications, 98, 104 Verocay bodies, 98, 100 Perivascular hyalinization, 15, 98, 101, 105, 128 Placental-like alkaline phosphatase (PLAP), 165, 168, 172, 179 Plasmablastic lymphoma, 185, 195 Plasma cell-rich thymoma immature T lymphoblasts, 40 polytypic distribution, 40 thymic epithelial cells, 40 Pleomorphic liposarcoma, 145 Pleomorphic mediastinal lymphoma, 185, 201 Primitive neuroectodermal tumor (PNETs) chromosome 22, 109 Ewing’s sarcoma, 109 immunohistochemical staining, 109 mesenchymal chondrosarcoma, 147 neuroblastoma, 109 neuroectodermal differentiation, 109 periodic acid-Schiff (PAS), 109 Psammomatous melanotic schwannoma, 98, 104 Pseudosarcomatous stroma, 29 R Rhabdomyoblastic cells, 185, 197 Rhabdomyomatous thymoma eosinophilic cytoplasm, 40 epithelial cells, 40 MyoD1 and myogenin, 40 224 Rhabdomyosarcomas (embryonal) alveola-like spaces, 135, 139 immunohistochemical staining, 135, 138 mediastinal lymph nodes, 135, 139 monotonous population, 135, 137 Myo-D1 and myogenin, 135, 138 sclerosing pattern, 135, 138 spindle-cell variants, 135, 139 “triton” tumor, 135, 140 S Schwannoma collagenous stroma, 89, 92 dense collagenous stroma, 98, 99 eosinophilic cytoplasm, 89, 91 fibrous capsule, 98 foci, Antoni type, 98, 100 ganglioneuroma, 89, 91 magnification, 89, 91 malignant neoplasms, 98, 103 multilocular cysts, 102 myxoid/edematous stroma, 98, 99 paucicellular, 89, 92 PNSTs, 98 S-100 protein, 98, 104 stromal collagenization, 98, 99 Verocay bodies, 98, 101 xanthoma cells, 98, 102 Seminoma anaplastic morphology, 165, 168 clear cell tumor, 165, 167 cluster of lymphoid cells, 165, 172 cystic degeneration, 165, 169 cytokeratins, 165, 169 cytoplasmic and nuclear features, 165, 167 diagnosis, 165 eosinophilic cytoplasm, 165, 169 epithelioid histiocytes, 165, 170, 171 fibroconnective tissue, 165, 167 fibrotic cyst wall, 165, 169 fibrous septa, 165, 166 fibrovascular stroma, 165, 166 fungal disease/sarcoidosis, 165, 170 granulomas, 165, 170 hyperchromatic nuclei and scattered mitoses, 165, 172 irregular nuclei and prominent nucleoli, 165, 168 lymphoid hyperplasia, 165, 171 OCT4, 165, 168 PLAP, 165, 168 round to oval nuclei, 165, 170 serpiginous cords, 165, 166 stromal fibrosis and hyalinization, 165, 172 tingible-body macrophages, 165, 171 tumor cells, 165 vascular spaces, 165, 166 vesicular nuclei and prominent nucleoli, 165 Small cell carcinoma adipocytes, 84 diagnosis, 83 necrosis, 83 transitions, 84 Solitary fibrous tumors (SFTs) amianthoid, 123, 125 atypical spindle-cell proliferation, 123, 131 cell population, 123, 124 Index characterization, 123 cytologic atypia, 123, 131 “dedifferentiated” component, 123, 131 epithelioid appearance, 123, 129 fascicles, 123, 124 hemangiopericytic proliferation, 123, 128 herringbone pattern, 123, 127 histologic features, 123, 130 hyalinized collagen, 123, 125 hyalinized fibrous tissue, 123, 130 hypercellularity, 123, 127 immunohistochemical markers, 123, 124 monotonous spindle cells, 123, 126 nuclear pleomorphism, 123, 132 osseous metaplasia, 123, 129 perivascular hyalinization, 123, 128 perivascular stromal collagenization, 123, 127 proliferation, 123, 126 residual islands, 123, 130 schwannian neoplasm, 123, 130 staghorn, 123, 129 STAT6 antibody, 123, 124 stromal alterations, 123, 125 stromal collagenization, 123, 125 tan-white cut surface, 123 Spindle-cell thymoma biphasic synovial sarcoma, 23 cystic degeneration, 25 cytokeratin and p63, 22, 23 homogeneous rubbery tissue, 21 hyalinization, 24 lumina, 26 lymphocytes, 21 macrocystic growth pattern, 26 metaplastic thymoma, 29 microcystic growth pattern, 25, 26 neuroendocrine markers, 27 papillary tufts, 23 perithymic fat, 31 schwannian neoplasms, 24 sclerosis and hyalinization, 22 serpiginous cords, 28 stromal sclerosis, 22, 24 thymic carcinoma, 29 whorling pattern, 21 Stromal hyalinization, 24 Stromal sclerosis DLBCL, 185, 191 reticular pattern, 185, 192 storiform pattern, 185, 198 Suster, S., 1–17, 19 Synovial sarcomas characterization, 150, 153 histologic variants, 150 monophasic atypical spindle cells, 150, 151 epithelioid pattern, 150, 152 MPNSTs, 150, 152 storiform pattern, 150, 152 soft tissue tumors, 150 spindle-cell proliferation, 150, 151 T T-cell receptor (TCR) genes, 203 Teratomatous lesions Index angiosarcoma, 158, 163 atypical endothelial cells, 158, 163 chondrosarcoma, 158, 164 components, 158 ectodermal and endodermal derivatives, 158 eosinophilic cytoplasm, 158, 164 epithelium and nodule, 158, 163 germ cell layers, 158 granulomas, 158, 160 immature teratomas, 158, 160–162 mature teratoma, 158–160 rhabdomyosarcomatous component, 158, 163 tumors, 158 yolk sac tumor and seminoma, 158, 161 Thymic carcinoid See Neuroendocrine carcinomas Thymic carcinoma abundant fibrous stroma, 51 adenocarcinomas, 53 anaplastic carcinoma, 54 autoimmune disorders, 48 basaloid carcinoma, 52 clear cell carcinoma, 51 colloid carcinoma, 53 cystic degeneration, 49 glycogen, 52 lymphoepithelioma, 50 lymphoplasmacytoid, 50 mucicarmine stain, 49 mucin-filled cysts, 49 mucoepidermoid carcinoma, 49 multilocular thymic cysts, 49 squamous cell carcinoma, 48 thymic epithelial neoplasms, 48 tumor cells, 48 Thymic epithelial neoplasms anterior mediastinum, 19 atrophic strands, 13 cystic dilatation, hyperplastic changes, lipoblastic cells, 142 lymphocytes, paraneoplastic syndromes, 19 primary and metastatic neoplasms, 199 small lymphocytic component, spindle cells, T-memory cells, WHO, 19 Thymic hyperplasia antiretroviral therapy, chemotherapy, cortical-medullary architecture, physiologic process, reactive process, Thymofibrolipoma, 13, 14 Thymolipoma adipose tissue, 13 hyalinized stroma, 13 lobulated fatty tissue, 13 Thymomas hypertension, 20 225 immunohistochemistry, 46–47 plasma cell-rich thymoma, 40 pulmonary embolism, 20 rhabdomyomatous, 40 spindle-cells (see Spindle-cell thymoma) V Vascular tumors angiosarcoma, 112, 121 atypical tumor cells, 112, 117 cystic lymphangioma, 112 epithelioid hemangioendothelioma, 112–114 immunohistochemical staining, 112, 122 mediastinal hemangiomas, 112, 113 metastatic carcinoma, 112, 117 osteoclast-type multinucleated cells, 112, 116 red blood cells, 114 signet-ring cell appearance, 112, 115 stromal changes, 112, 115 trabeculae, 112, 119 W WHO See World Health Organization (WHO) World Health Organization (WHO), 57 atypical thymoma, 41–45 lymphocyte-rich, 32–36 mixed lymphoepithelial thymoma, 36–39 Y Yolk sac tumor AFP, 165, 173, 179 anaplasia and nuclear pleomorphism, 165, 179 anastomosing cords, 165, 177 biopsy, 165, 178 clear cell features, 165, 176 clusters and cords, 165, 177 cribriform spaces and myxoid stroma, 165, 177 cytologic features, 165, 179 endodermal sinus pattern, 165, 174, 175 enteric pattern, 165, 176 focal gland formation, 165, 178 germ cell tumors, 165, 172 glandular-alveolar pattern, 165, 173 glandular structures, 165, 175 glomeruloid structures, 165, 174 glypican-3, 165, 180 hepatoid, 165, 178, 179 high mitotic activity, 165, 174 hyperchromatic tumor cells, 165, 175 morphologic appearance, 165, 173 multinodular appearance, 165, 175 Schiller-Duval bodies, 165, 173, 176 sheets and discrete trabeculae, 165, 176 spindle-cell appearance, 165, 178 vitelline pattern, 165, 174 ... (Figs 5.1, 5 .2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 5.10, 5.11, 5. 12, 5.13, 5.14, 5.15, 5.16, 5.17, 5.18, 5.19, 5 .20 , 5 .21 , 5 .22 , 5 .23 , 5 .24 , 5 .25 , 5 .26 , 5 .27 , 5 .28 , 5 .29 , 5.30, 5.31, 5. 32, 5.33,... remarkable consistency of t(11 ;22 )(q24;q 12) Cancer Genet Cytogenet 1988; 32: 229 –38 Weitzner S Adjacent malignant schwannoma and neurofibroma of intrathoracic vagus Am Surg 1976; 42: 866–70 Wick MR, Swanson... unknown etiology S Suster (ed.), Atlas of Mediastinal Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4939 -26 74-9_5, © Springer Science+Business Media, LLC 20 15 Tumor type Hemangioma Lymphangioma