HANDOUT
ILLINOIS REGISTRY OF ANATOMIC PATHOLOGY
RUSH UNIVERSITY MEDICAL CENTER
NOVEMBER 24, 2003
Presenter: Reshma Ariga, MD
Attending: Alexander C Templeton, MD
Diagnosis: Myositis Ossificans (of the foot).
Malignant
Extraskeletal osteosarcoma
Epithelioid sarcoma
Clear cell tumor of tendon sheath
Synovial sarcoma
Benign/reactive
Fibro-osseus pseudotumor of the digits (FOPD)
Fibrodysplasia ossificans progressiva (FDOP)
Ossifying fibromyxoid tumor
NoraÕs lesion
Nodular fasciitis
Fibroma of tendon sheath
Giant cell tumor of tendon sheath
Calcifying aponeurotic fibroma
Tumoral calcinosis
Plantar fibromatosis
á Microscopic: Classic zonation pattern with a peripheral zone of osteoid lined by a uniform layer of osteoblasts, and a central zone composed of loosely textured vascular spindle cell proliferation. There are mitosis but no atypical forms.
á Myositis Ossificans is one family of reactive conditions including proliferative fasciitis, decubitus fasciitis, post traumatic heterotopic bone formation in scars and hip replacement, FOPD, and FDOP.
á Bone morphogenetic proteins (BMPs) are part of a family of 43 proteins that include the transforming growth factor Beta like genes.
á There are seven major BMPs that act on bone and induce bone formation in mesenchymal cells. Most of these are able to induce many of the characteristics of osteoblasts in tissue culture of vascular pericytes. Implantation of these materials lead to cartilaginous proliferation followed by the usual embryological process of enchondral ossification.
á Osteosarcoma cells make all 7 BMPs in excess, in myositis ossificans BMP type 1, 4 and 6 are found in high concentration. In fibrodysplasia ossificans progressiva the receptor BMP4 is constituitively overactive.
á BMPs are being used to induce bone formation where you want it.
1. Shafritz A B and Kaplan F S. Differential expression of Bone and
Cartilage related genes in Fibrodysplasia Osssificans Progressiva, Myositis
Ossificans Traumatica, and Osteogenic sarcoma. Clinical Orthopedics and Related Research 1998; 346:46-52.
2. Wozney J M and Rosen Vicki. Bone Morphogenetic Protein and Bone
Morphogenetic Gene Family in Bone Formation and Repair. Clinical Orthopedics
and Related Research 1998;
346:26-37.
3. Lanchoney T F, Olmsted E A, Shore E M, Kaplan
F S et al. Clinical Orthopedics and Related Research 1998; 346:38-45.
4.
Bancroft L W, Peterson J J, Nomikos G C, Murphey M D, et al. Soft tissue tumors of the lower
extremeties. Radiologic Clinics of
North America 2002; 40(5).
Presenter: Tera Jones, MD
Attending: Paolo Gattuso, MD
Diagnosis: Adrenal cortical neoplasm of indeterminate malignant potential
Important Differential
Diagnosis:
Adrenal
cortical adenoma
Adrenal
cortical adenocarcinoma
9
features have been correlated with a poor clinical prognosis in the pediatric
population including:
1. Atypical mitotic figures
2. Necrosis
3. Venous invasion
4. Capsular invasion
5. > 15 mitoses/ 20 HPF
6. Weight >400 g
7. Tumor size >10.5 cm
8. Invasion into the vena cava
9. Extension into peri-adrenal soft tissues or adjacent
organs
No
one feature should be used alone to predict prognosis. The suggested guidelines are as
follows:
1. Up to 2 criteria present suggests a benign clinical
outcome
2. Three criteria present suggests an indeterminate
malignant potential
3. Four or more criteria present suggest a poor clinical
outcome
Immunohistochemistry and Electron microscopy are not
especially useful.
Adrenal cortical neoplasms in the pediatric
population are uncommon. They
historically, they have been classified according to the established adult
criteria proposed by Weiss et al.
It has been recognized by many investigators that pediatric neoplasms,
may appear more malignant than their adult counterparts, yet behave in a
clinically benign fashion. While a few authors have tried to classify the
lesions, the largest study was recently published by Dr Weineke et al of the
AFIP investigating 83 such tumors in the pediatric population. They suggested
the above criteria and guidelines based on clinical follow-up.
References
1. Aubert, S; Wacrenier, A et al. ÒWeiss System Revisited: A Clinical pathologic and
Immunohistochemical Study of 49 Adrenocortical Tumors.Ó 26(12): 1612-1619, 2002.
2. Bugg, M, Ribeiro, R et al. ÒCorrelation of Pathologic Features With Clinical Outcome in
Pediatric Adrenocortical Neoplasia A Study of a Brazilian Population.Ó Am J Clin Pathol 101: 625-29, 1994.
3. Ciftci, A; Senocak, M; Tanyel, F; Buyukpamukcu,
N. ÒAdrenocortical tumors in
children.Ó Journal of Pediatric
Surgery 36(4): 549-54, 2001.
4. Lack, E.
Adrenal Cortical Carcinoma and Adrenal Cortical Neoplasms in
Children. Tumors of the Adrenal
Gland and Extra-adrenal Paraganglia, fascicle 19. Washington, DC:
Armed Forces Institute of Pathology, 1997: 123-68.
5. Sandrini, R; Ribeiro, R; Delacerda, L. ÒChildhood Adrenocortical Tumors.Ó The J of Clin Endocrinology &
Metabolism 82(7): 2027-2031, 1997.
6.
Sredni, S; Alves, V et al. ÒAdrenocortical
tumours in children and adults: a
study of pathological and proliferation features.Ó Pathology 35: 130-35, 2003.
7.
Stojadinovic, A; Brennan, M et al.
ÒAdrenocortical Adenoma and Carcinoma: Histopathological and Molecular Comparative Analysis.Ó Mod Pathol 16(8): 742-51, 2003.
8.
Teinturier, C; Pauchard, MS et al.
ÒClinical and Prognostic Aspects of Adrenocortical Neoplasms in
Childhood.Ó Med and Ped Onc 32:
106-111, 1999.
9.
Weiss LM. ÒComparative
histopathologic study of 43 metastasizing and nonmetastasizing adrenocortical
tumors.Ó Am J Surg Pathol 8:
163-9, 1984.
10.
Weiss LM, Medeiros LJ, Vickery AL.
ÒPathologic features of prognostic significance in adrenocortical
carcinoma.Ó Am J Surg Pathol
13:202-6, 1989.
11.
Wieneke, J; Thompson, L;
and Heffess, C. ÒAdrenal Cortical
Neoplasms in the Pediatric Population:
A Clinicopathologic and Immunophenotypic Analysis of 83 patients.Ó Am J Surg Pathol 27(7): 867-81, 2003.
12.
Wolthers, OD, Cameron, FJ, Scheimberg, I et al. ÒAdrogen secreting adrenocortical
tumours.Ó Arch Dis Child 80: 46-50,
1999.
Presenter: Juan-Miguel Mosquera, MD
Attending: Jerome M. Loew, MD
Diagnosis: Thymic carcinoma with neuroendocrine differentiation
á Thymic infiltration by an extrathymic carcinoma, either metastasis or direct extension.
á Microscopic: May have morphologic features of any of several subtypes of thymic carcinoma, including epidermoid (keratinizing and non-keratinizing), lymphoepithelioma-like carcinomas, small cell carcinoma, or adenocarcinoma of the thymus. Cells are reactive for one or more neuroendocrine markers.
á Immunohistochemistry: synaptophysin, chromogranin and/or NSE highlight neuroendocrine differentiation of the tumor cells. In addition, small neuroendocrine cells can also be demonstrated using these stains. CD5 is positive in thymic carcinoma.
á Electron microscopy: demonstrates dense-core granules and cell junctions
Neuroendocrine differentiation is a common feature in thymic carcinomas. Focal expression of neuroendocrine markers is found in about 68% of cases. Neuroendocrine differentiation is not restricted to a specific histologic type of thymic carcinoma. No specific genetic alteration in thymic carcinomas has been correlated with neuroendocrine differentiation. This data suggests that a distinction between high-grade thymic carcinomas with neuroendocrine differentiation and primary neuroendocrine carcinomas of the thymus may not be warranted. This case illustrates that these two types of thymic tumors may well be a spectrum of related carcinomas.
1. Histological typing of tumors of the thymus. World
Health Organization International Histological Classification of Tumors, 2nd Ed. Heidelberg: Springer-Verlag,
1999: 5-6
2. Lauriola L, Erlandson RA, and Rosai J.
Neuroendocrine differentiation is a common feature of thymic carcinoma. Am J
Surg Pathol 1998;
22(9):1059-1066
3. Hishima T et al. Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma. Hum Pathol 1998; 29:330-338
4. Kuo T-k. Frequent presence of neuroendocrine
small cells in thymic carcinoma: a light and immunohistochemical study. Histopathology 2000; 37:19-26
5. Suster S and Moran CA. Neuroendocrine neoplasms of the mediastinum. Am
J Clin Pathol 2001; 115 (Suppl
1): S17-S27
6. Moran CA and Suster S. Neuroendocrine
carcinomas (carcinoid tumor) of the thymus. Am J Clin Pathol 2000; 114: 100-110
7. Moran CA and Suster S. Thymic neuroendocrine carcinomas with combined features ranging from well-differentiated (carcinoid) to small cell carcinoma. Am J Clin Pathol 2000; 113: 345-350
8. Hishima T et al. CD5 expression in thymic carcinoma. Am J
Pathol 1994; 145(2): 268-275
9. Kornstein MJ and Rosai J. CD5 labeling of
thymic carcinomas and other nonlymphoid neoplasms. Am J Clin Pathol
1998; 145(2): 722-726
10. Tateyama H et al. Immunoreactivity of a new CD5 antibody with
normal epithelium and malignant tumors including thymic carcinoma. Am J Clin
Pathol 1999; 111:235-240
Presenter: Sophie Z. Aalaei, M.D.
Attending: Alexander C. Templeton, M.D.
Diagnosis: Segmental colitis associated with Diverticulitis.
Ulcerative colitis
CrohnÕs disease
Most
papers on this subject are incidental case reports, and provide no
epidemiological data on the disease progression. The best data available
consist of two studies which when combined, had described and followed 46
patients. Many of these patients underwent resection of the involved part of
the bowel. Of these 46 patients,
only 5 went on to develops inflammatory bowel disease. This suggests that
diverticular disease is the driving force behind the development of
inflammatory bowel disease like changes in most individuals with
diverticulitits. Surgical resection of the involved segment of bowel is curative
in these individuals.
1. Makagupay L.M., et.al. Diverticular disease-associated chronic colitis. American Journal of Surgical Pathology 1996; 20:94-102.
2. Van Rosendaal G.M.A. Segmental colitis complicating diverticular disease. Canadian Journal of Gastroenterology 1996; 10(6): 361-4.
3. Deutsch S.F. et.al. Areomonas sobria-associated left-sided segmental colitis. American Journal of Gastroenterology 1997; 92:2104-2108.
4. Pereira M.C. Diverticular disease-associated colitis: progression to severe chronic ulcerative colitis after sigmoid surgery. Gastrointestinal endoscopy 1998; 48:520-3.
5. Goldstein N.S., et.al. CrohnÕs Colitis-like Changes in Sigmoid Diverticulits Specimens is Usually an Idiosynchratic Inflammatory Response to the Diverticulosis Rather Than CrohnÕs Colitis. American Journal of Surgical Pathology 2000; 24(5): 668-75.
6. Jani N. et.al. Segmental Colitis Associated with Diverticulosis. Digestive Diseases and Sciences 2002; 47:1175-81.
7. Gushlandi M. Segmental colitis: so what? European Journal of Gastroenterology and Hepatology 2003; 15:1-2.
Case
# 5
Presenter: Rohan
John, MD
Attending:
Elizabeth Cochran, MD
Diagnosis:
Medulloblastoma, large cell/anaplastic subtype
Atypical
teratoid/rhabdoid tumor
Metastatic
small cell carcinoma
Malignant
astrocytoma, Ependymoma, Pilocytic astrocytoma
á Microscopic:
areas of sheets of small round blue cells with Homer Wright rosettes;
other areas with large cells, the nuclei of which are angular, pleomorphic and
show molding. Abundant mitoses and
apoptotic bodies are seen, and cell wrapping is present.
á Immunohistochemistry: Synaptophysin positivity
supports neuronal differentiation.
EMA, cytokeratin AE1/AE3, vimentin, chromogranin, and neurofilament are
negative. GFAP is focally positive
highlighting reactive astrocytes.
An elevated MIB-1 index is consistent with a highly proliferative
tumor.
Medulloblastoma is an
embryonal cerebellar tumor primarily occurring in children, and usually with
neuronal differentiation. The
classic medulloblastoma consists of sheets of small round blue (primitive/
undifferentiated) cells. The large
cell/anaplastic subtype contains large cells with abundant mitoses and
apoptotic bodies, and shows cell wrapping. In addition and specifically, the Òlarge cell typeÓ has
round cells with nucleoli, while the Òanaplastic typeÓ has angular, pleomorphic
cells with nuclear molding.
The large cell/anaplastic
subtype has a poorer prognosis compared to the classic and nodular/desmoplastic
subtypes. A variant of the latter
showing extreme nodularity has the best prognosis.
The medulloblastoma is
currently thought to arise from progenitors in the external granular cell layer
in the cerebellum. In some 50% of
cases, a 17p deletion is detectable, and c-myc overexpression has been
associated with large cell/anaplastic morphology.
Medulloblastoma should be
differentiated from the more recently described atypical teratoid/rhabdoid
tumor that is usually seen in children less than 2 years, contains the typical
Òrhabdoid cellsÓ, frequently along with primitive small cells, epithelial, or
mesenchymal elements, and manifests a diverse immunophenotype, including EMA
positivity.
1. Eberhart CG, Burger PC. Anaplasia and grading in medulloblastomas. Brain Pathol.
2003; 13:376-85.
2. Brown HG, Kepner JL, Perlman EJ, Friedman HS,
Strother DR, Duffner PK, Kun LE, Goldthwaite PT, Burger PC. "Large cell/anaplastic"
medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol. 2000; 59:857-65.
3. McManamy CS, Lamont JM, Taylor RE, Cole M, Pearson
AD, Clifford SC, Ellison DW; United Kingdom Children's Cancer Study Group. Morphophenotypic variation predicts
clinical behavior in childhood non-desmoplastic medulloblastomas. J Neuropathol Exp Neurol. 2003;
62:627-32.
4. Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE,
Duffner PK, Friedman HS, Strother DR, Burger PC. Histopathologic grading of medulloblastomas: a Pediatric
Oncology Group study. Cancer 2002;
94:552-60.
5. Burger PC, Yu IT, Tihan T, Friedman HS, Strother DR,
Kepner JL, Duffner PK, Kun LE, Perlman EJ. Atypical teratoid/rhabdoid tumor of the central nervous
system: a highly malignant tumor of infancy and childhood frequently mistaken
for medulloblastoma: a Pediatric Oncology Group study. Am J Surg Pathol. 1998; 22:1083-92.
6. WHO Classification of Tumors 2000: Pathology &
Genetics of the Tumours of the Nervous System. Eds, Kleihues P & Cavenee WK.
Presenter:
Adil Zarif, M.D.
Attending:
Pincas Bitterman, M.D.
Diagnosis:
Sertoli
Cell Tumor, Poorly Differentiated, with Malignant Stromal Heterologous Elements
and Necrosis
Important
Differential Diagnosis
á
Sertoli-Leydig Cell
Tumor
á
Rhabdoid Tumor
á
Rhabdomyosarcoma
á
Granulosa Cell Tumor
á
Endometrioid Carcinoma
á
Carcinoid Tumor
á
Characterized by a predominant pattern of hollow or solid tubules,
dispersed within a fibrous stroma that contains no Leydig cells
á
Sarcomatoid and solid pattern is also present
á
Heterologous elements composed of malignant rhabdomyoblastic
differentiation
á Immunohistochemistry of Sertoli Cell Component:
á Positive Ð Inhibin and Cytokeratin
á Negative Ð EMA and PLAP
á Positive Ð Desmin, MSA, and Vimentin
á Negative Ð SMA, EMA, Cytokeratin, and Inhibin
Sertoli cell tumor of the ovary is a very
uncommon tumor described mainly in case reports. It has similar morphologic characteristics to Sertoli-Leydig
cell tumors of the ovary without Leydig cells. Heterologous elements are seldom seen. Patients typically are less than 30
years of age and present with a palpable abdominal mass. Two-thirds of tumors are hormonally
active: 70% secrete estrogen while 16% secrete androgens. Their prognosis is closely related to
their stage and degree of differentiation.
1. Nolan T, et al.: Recurrence of a Gonadal
Stromal Cell Tumor (Sertoli Leydig Cell with Heterologous Elements) in a
Teenager. Gynecologic Oncology 1983;15:111-119.
2. Guerard M, et al.: Ovarian Sertoli-Leydig Cell Tumor with
Rhabdomyosarcoma: An Ultrastructural Study. Ultrastructural Pathology 1982;3:347-358.
3. Scorpio R, et al.: Pathologic Case of the Month. Arch. Pediatric
Adolescent Med. 2000;154(4):419-420.
4. Young R, et al.: Ovarian Sertoli-Leydig cell tumors. A clinicopathologic analysis of
207 cases. Am. J. Surg. Pathol. 1985;9:543-569.
5. Prat J, et al.: Ovarian Sertoli-Leydig cell tumors with heterologous elements. (ii)
Cartilage and skeletal muscle: a clinicopathologic analysis of twelve cases.
Cancer 1982;50:2465-2475.
6. Young R, et al.: Ovarian Sertoli-Leydig cell tumors with heterologous elements. (i)
Gastrointestinal epithelium and carcinoid: a clinicopathologic analysis of
thirty-six cases. Cancer 1982;50:2448-2456.
7. Young R and Scully R: Sex Cord-Stromal, Steroid Cell,
and Other Ovarian Tumors with Endocrine, Paraendocrine, and Paraneoplastic
Manifestations. BlausteinÕs Pathology of the Female Genital Tract 2002;Chapter 19:905-966.
Presenter: Frances Manosca, MD
Attending: Melvin Schwartz, MD
Diagnosis: Multilocular renal cyst (Cystic nephroma)
á Cystic partially differentiated nephroblastoma
á Cystic renal cell carcinoma
á Renal retention cyst
á Cystic renal dysplasia
Septa may not contain epithelial cells with clear cytoplasm or
skeletal muscle fibers
á Immunohistochemistry: AE1/AE3 highlight the epithelial nature of the cysts and tubules; EMA shows variable reactivity. SMA demonstrates the smooth muscle nature of the material in the stroma.
á Electron microscopy: Cells lining the cysts have short microvilli, closely resembling the epithelium of the collecting tubules.
á Benign neoplasm which occurs in boys less than 4 years old, second peak in women over 30 years old
á Cannot be reliably distinguished from malignant neoplasms namely cystic renal cell carcinoma, by radiological studies
á Require complete resection with clear margins because of uncertainty of diagnosis and to evaluate microscopically for classification
á Histologically, related to cystic partially differentiated nephroblastoma and cystic nephroblastoma
1. Eble JN, Bonsib SM: Extensively Cystic Renal Neoplasms: Cystic Nephroma, Cystic Partially Differentiated Nephroblastoma, Multilocular Cystic Renal Cell Carcinoma, and Cystic Hamartoma of Renal Pelvis. Seminars in Diagnostic Pathology, Vol 15, No 1:2-20,1998
2. Joshi VV,Beckwith JB: Multilocular cyst of the kidney (cystic nephroma) and cystic, partially differentiated nephroblastoma, terminology and criteria for diagnosis. Cancer 64:466-479,1989
3. Nagao T,Sugano I, Ishida Y, Tajima Y, Masai M, Nagakura K, Matsuzaki O, Kondo Y, and Nagao K: Cystic partially differentiated nephroblastoma in an adult: an immunohistochemical, lectin histochemical and ultrastructural study. Histopathology 35:65-73,1999