HANDOUT
THE UNIVERSITY OF ILLINOIS AT CHICAGO
FEBRUARY 23, 2004
CASE 1
Resident: Lawrence
Jennings, MD, PhD
Attendings: Gregorio
Chejfec, M.D.
Suman Setty, MD, PhD
Introduction: Primary extragonadal germ cell tumors account for 5-7% of all germ cell tumors and presumably arise from a failure in migration of primordial germ cells during embryogenesis. Aneuploidization results in a premalignant cell which has been called a carcinoma-in-situ cell (CIS cell). These CIS cells retain the immunophenotype of the primordial germ cell/gonocyte from which they arose.
Gross Examination: A well-circumscribed retroperitoneal mass (5.5cm)
that was soft, tan and partly necrotic.
Microscopic Examination: Sheets of monomorphic, large cells separated into
nests by fibrovascular septae with a prominent lymphocytic infiltrate are seen.
On high power, the large cells have clear cytoplasm and well defined
cytoplasmic margins.
Immunohistochemistry: The
large cells are positive for CD10 and c-kit and negative for PLAP.
Electron Microscopy: The
large cells have a serpiginous pattern in the nucleolus that is characteristic
of seminoma and dysgerminoma.
Conclusion: This
case is an example of a germ cell tumor occurring in the retroperitoneum,
without any identifiable tumor in the testes. PLAP is detected in over 90% of seminomas but a small subset
are negative. The high rate of positivity
for c-kit reported in the literature makes this a useful marker. In addition, this
case demonstrates CD10 positivity which has not been previously described in
seminomas. Like c-kit, CD10 is
also positive in CIS cells and primordial germ cells and therefore likely
reflects the retained immunophenotype of the primordial germ cell.
Selected References:
1. Sakuma Y, et al. Alterations of the c-kit gene in
testicular germ cell tumors. Cancer Sci, 94, 486-491, 2003.
2. Robinson L, et al. Germ cell specific expression of
c-kit in the human fetal gonad. Molecular Human Reproduction, 7, 845-852, 2001.
3. Bokemeyer C, et al. Extragonadal germ cell tumors:
relation to testicular neoplasia and management options. APMIS, 111, 49-63,
2003.
4. Rouiller-Fabre V, et al. Development of the foetal and
neonatal testis. Andrologia, 35, 79-83, 2003.
5. Jaume O, et al. CD10 expression in epithelial tissues
and tumors of the gynecologic tract: a useful marker in the diagnosis of
mesonephric, trophoblastic, and clear cell tumors. Am J Surg Pathol, 27,
178-186, 2003.
6. Rajpert-de Meyts E, et al. The emerging phenotype of
the testicular carcinoma in situ germ cell. APMIS, 111, 267-79, 2003.
Case 2
Fellow: Amy Lin, MD
Attending: Robert
Folberg, MD
Diagnosis: Primary large
B-cell lymphoma of the retina and brain
Introduction: Primary large B-cell lymphoma of the retina is a subset of primary central nervous system lymphoma. It typically occurs in adult patients (median age: 50-60 years) with a slight male predominance. Retinal involvement is usually bilateral, and may occur before or after brain involvement. The diagnosis is based on vitreous cytology. The vitreous biopsy is often hypocellular and shows degenerative changes; multiple biopsies may be required to establish the diagnosis. Treatment includes whole brain and eye radiation with or without chemotherapy.
Gross Examination: Silicone oil is present in the vitreous cavity. The choroid is diffusely thick. The retina demonstrates nodular thickening with creamy white lesions. There is a sharp demarcation between the retina and choroid.
Microscopic examination: There is a marked difference between the nature of the choroidal and retinal infiltrates. The choroidal infiltrate is composed of a mixed population of lymphocytes and plasma cells. Normal choroidal melanocytes are also present. The retina and retinal pigment epithelium are replaced by a cellular infiltrate composed of large, pleomorphic cells and atypical mitotic figures. In some areas, the retina is necrotic.
Immunohistochemistry: The cells in both the retina and the choroid stain positive for CD45. In the choroid, an equal proportion of cells are positive for CD20 and CD3. Bcl-2 is positive in some T-cells of the choroid. In the retina, the cells stain exclusively with CD20 and are negative for CD3. These cells also stain positive for bcl-2.
Radiographic findings: There are infiltrative, heterogeneously enhancing masses in the paramedian frontal lobes that involve the corpus callosum.
References:
Clinical and histologic diagnosis of primary retinal lymphoma
Radiographic appearance
Immunohistochemistry in primary retinal lymphoma
Gene rearrangements in primary retinal lymphoma
Interleukin-10 in primary retinal lymphoma
Treatment of primary retinal lymphoma:
Case 3
Resident: Jigna
Jani, M.D.
Attendings: Grace Guzman,
M.D.
Tibor Valyi-Nagy, M.D., PhD
Gregorio Chejfec, M.D.
Diagnosis: Intravascular
extension of osteosarcoma of pelvis to heart and pulmonary arteries
Differential diagnosis of
right atrial mass
1) Dedifferentiated chondrosarcoma
2) Mesenchymal chondrosarcoma
3) High grade chondrosarcoma
4) Myxofibrosarcoma
5) Chondromyxoid fibroma like osteosarcoma
Introduction: Osteosarcoma is a malignant neoplasm particularly of long bones with focal production of osteoid, occurring mainly in second decade of life with male predominance. Osteosarcoma (OS) of the pelvis is rare, accounting for only 7-9% of all osteosarcoma. Overall survival of pelvic OS is 20 - 47% and is worse than extremity sarcomas.
Gross examination (heart lesion) consisted of multiple fragments of tan white, lobulated, firm, glistening soft tissue with a cartilaginous consistency.
Microscopic lesion (of the heart) consisted of irregular chondromyxoid lobules separated by some fibrous tissue.The cells in the matrix were pleomorphic, hyperchromatic, few binucleate with lacunae. The periphery of lobules were hypercellular composed of stellate to spindle shaped, pleomorphic, hyperchromatic cells with a few mitotic figures.
Microscopic lesion from the decompressive foraminotomies (L4-S1) consisted of fragments of primitive appearing spindle to oval shaped cells with scant eosinophilic cytoplasm and hyperchromatic nuclei with prominent nuclei.There was brisk mitosis at 12/10 HPF. There were islands of osteoid and some streamer osteoid formed by the tumor cells and the osteoid were lacking the characteristic rimming by the osteoblasts.
Immunohistochemistry in both lesions were diffusely positive for vimentin, Ki-67 proliferation index showed 60% staining and there was focal positivity for S-100 in the cardiac tumor.
The subtypes of sarcomas which invade the IVC are leiomyosarcomas and chondrosarcomas. Other tumors which may invade the IVC are renal, hepatocellular, and adrenal carcinoma, testicular tumors and WilmÕs tumor. Intravascular growth of the tumor may be associated with chondroid, myxoid or chondromyxoid pattern.
Conclusion: This is a rare case of osteosarcoma with intravascular extension to the heart and pulmonary arteries.
Selected references:
1) Ozaki T, Osteosarcoma of the pelvis: experience of the
Cooperative Osteosarcoma Study Group.
J Clin Oncol. 2003 Jan 15; 21(2):334-41.
2) Wakasa K, Sakurai M, Uchida A, Yoshikawa H, Maeda A Massive pulmonary tumor emboli in osteosarcoma. Occult and fatal complication Cancer. 1990 Aug 1; 66(3):583-6.
3) Gopal AS, Stathopoulos JA, Arora N, Banerjee S, Messineo F. Differential diagnosis of intracavitary tumors obstructing the right ventricular outflow tract. J Am Soc Echocardiogr. 2001 Sep; 14(9):937-40.
4) Yilmaz M, Farsak B, Altundag MK, Demircin M, Ozkutlu S, Pasaoglu I.Isolated cardiac metastasis of osteosarcoma. J Exp Clin Cancer Res. 2000 Sep; 19(3):395-7.
5) Chow LT, Lin J, Yip KM, Kumta SM, Ahuja AT, King WW, Lee
JC.
Chondromyxoid fibroma-like osteosarcoma: a distinct variant of low-grade
osteosarcoma. Histopathology. 1996 Nov; 29 (5):429-36.
6) Giuliano CT, Kauffman WM, Haller JO, Fletcher BD, Rao SP.
Inferior vena cava-right atrial tumor thrombus in malignant pelvic bone tumors
in children. Pediatr Radiol 1992; 22(4):303.
Case 4
Fellow: Gabriel C.
Calilao, MD
Attending: Gregorio Chejfec, MD
DIAGNOSIS:
Metastatic high-grade sarcoma (primary site, prostate)
Differential Diagnosis:
1. Embryonal rhabdomyosarcoma, spindle cell variant
2. Leiomyosarcoma
3. Malignant phyllodes tumor
4. Carcinosarcoma
5. Stromal sarcoma
Clinical History: 69 year old gentleman who presented with prostatism and symptoms of urinary obstruction 10 years ago. A prostatectomy was performed. 7 years later, there was a new discovery of one nodule in each lung. These nodules remained stable for three years but recently showed rapid change in size. One of these nodules was resected.
Gross Description: Multiple nodules were seen, the largest is 5.5 cm in widest diameter.
Microscopic Description: The tumor is composed of spindle cells arranged in long and short interlacing fascicles, and storiform patterns. There are scattered pleomorphic cells, some having a rhabdomyoblastic appearance, Mitotic index averaging up to 15/hpf.
Immunohistochemical profile: Vimentin (++++), MSA (+), Desmin (+)
Myogenin, Myoglobin, S-100 (-)
Malignant neoplasms of mesenchymal in origin are rare in the prostate approximately less than 1% of all malignant neoplasms. The clinical symptomatology is similar with prostatic adenocarcinoma. The treatment consists of surgery (radical prostatectomy), chemotherapy or radiation therapy (or a combination of the 3). Prognosis is poor ranging from 10 to 109 months. Metastasis commonly occurs to the lungs, bones and lymph nodes/liver (in descending order).
Selected references:
1. Gaudin P, et al. Sarcomas and related proliferative lesions of specialized prostatic stroma: A clinicopathologic study of 22 cases. Am J Surg Path. 1998; 22(2): 148-162.
2. Cheville et al. Leiomyosarcoma of the prostate. Cancer 1995; 76:1422-7.
3. Fukawa et al.
Prostatic carcinosarcoma: A case report and review of the literature
Int J Urol 2003; 100: 108-113.
4. Young R et al. AFIP Fascicle. Tumors of the prostate gland, seminal
vesicles, male urethra, and penis.
Page 257-288
5. Yamamoto S et al. Malignant phyllodes tumor of the
prostate. Int J Uro. 2000;7(10):378-381
6. Dundore et al. Carcinosarcoma of the prostate. Cancer 1995;76(6);1035-1042
Case 5
Resident: Vladimir Vidanovic,
M.D.
Attending: Hongyu Ni, M.D, PhD
Diagnosis: Multicentric
Castleman Disease (MCD) and Kaposi Sarcoma
Differential Diagnosis: Post Transplant Lymphoproliferative Disorder
Plasmacytoma
Kaposi sarcoma
Multicentric Castleman Disease (MCD)
Introduction: Multicentric Castleman`s Disease and Kaposi sarcoma are associated with immunocompromised status, but in vast majority of cases these entities are occurring separately, regardless of underlying clinical condition. In almost 100% of patients with Kaposi sarcoma, HHV-8 is detectable using molecular methods as well as in a smaller proportion of patients with features of MCD alone. According to the modern literature, the number of patients with clinicopathologic evidence of both is rising. Almost exclusively, these patients are HHV-8+. The median survival time of "double hit" patients is related to serum levels of IL-6.
Pertinent findings: The immunodefficient patients with clinical and pathologic evidence of Kaposi sarcoma (nodal or extranodal) present with myriad MCD-associated symptoms, including lymphadenopathy, edema, effusions, splenomegaly, neurological changes and autoimmune-like manifestations. The associated laboratory findings are anemia, hyperglobulinemia, hypoalbuminemia, proteinuria and thrombocytopenia.
Treatment: Low survival rates of conventional therapy for Kaposi sarcoma alone or MCD alone. Promising clinical trials with h-anti IL-6 receptor antibodies are underway.
References:
1. Frizzera
G. Castleman`s disease and related disorders. Semin Diagn Pathol 1988;5:
346.
2. Nakamura
H, Nakaseko C, Ishii A, et al. Chromosomal abnormalities in Castleman`s disease
with high levels of serum interleukin-6.
Rinsho Ketsueki 1993; 34:212.
3. Parravicini
C, Corbellino M, Paulli M, et al. Expression of a virus derived cytokine, KSHV
vIL-6 in HIV seronegative Castleman`s disease, Am J Pathol 1997; 151:1517.
4. Foster
CB, Lehrnbecher T, et al. IL-6 promoter polymorphism is associated with
lifetime risk of development of Kaposi sarcoma, Blood 2000; 96(7):2562.
5. Bollen
JM, Polstra AM, Weel JF, et al. Multicentric Castleman`s disease and Kaposi
sarcoma in a cyclosporine treated HIV negative patient. Blood Disord 2003; 3:3.
Resident: Menchu G.
Ong, MD
Medical student IV:
Richard Perrin, PhD
Attending: Tibor
Valyi-Nagy, MD, PhD
Diagnosis: Subependymal giant cell cell
astrocytoma
Differential
Diagnosis: 1. Pilocytic
astrocytoma
2. Gemistocytic astrocytoma
3. Subependymal nodule associated with neurofibromatosis-1
Introduction: Subependymal giant cell astrocytoma is most commonly associated with tuberous sclerosis complex, however, SEGA may rarely occur outside tuberous sclerosis and rare cases of combined neurofibromatosis-1 and tuberous sclerosis complex have been reported. We present a rare case of coincidental neurofibromatosis-1 and tuberous sclerosis.
Clinical Presentation: 24-year-old male, previously diagnosed with neurofibromatosis-1 who presented with seizures.
Gross Description: Exophytic, solid, well-defined mass arising in the wall of the lateral ventricle in the region of the foramen of Monro
Microscopic Description: Wide spectrum of astroglial phenotypes ranging from polygonal cells with abundant, glassy cytoplasm to smaller, more elongate elements within a variably fibrillated matrix. Calcification and multinucleation are common.
Immunohistochemistry: Polygonal cells are variably positive for neurofilament and GFAP, while the elongated cells are positive for GFAP. Ki-67 shows a proliferation index of <3%.
References:
Resident: Victoria
Alagiozian-Angelova, M.D.
Attendings: Elliot
Weisenberg, M.D.
Gregorio Chejfec, MD
DIAGNOSIS:
Undifferentiated (embryonal) sarcoma of the liver
DIFFERENTIAL DIAGNOSIS:
1) Hepatic angiosarcoma
2) Embryonal Rhabdomyosarcoma
3) Sarcomatoid hepatocellular carcinoma
4) Anaplastic small cell hepatoblastoma
5) Malignant fibrous histiocytoma/Undifferentiated pleomorphic sarcoma
6) Mesenchymal hamartoma
Introduction: This is a rare hepatic tumor occurring mainly in children and young adolescents. The treatment is surgical excision with chemotherapy and/or radiation. There is high rate of local recurrence, distant metastases are also possible. Survival is much better than it was initially reported.
Gross Examination: Single large cystic and solid mass located in the right liver lobe with extensive necrosis and hemorrhage surrounded by a pseudocapsule. The tumor can reach 30cm in maximum dimension.
Microscopic examination: Spindle and stellate cells with ill-defined borders and scant cytoplasm suspended in loose myxoid stroma. Bizarre huge cells with hyperchromatic nuclei and giant multinucleated cells are common. Mitosis and apoptosis are abundant. Typically the tumor cells have scattered intracytoplasmic and extracellular eosinophillic globules, which represent lysosomal globules, composed of phagocytosed by the tumor cells apoptotic bodies. They are PAS positive and resist diastase digestion. The interface with the adjacent liver has entrapped hepatocytes and bile ducts, some of which could be cystically dilated.
Immunohistochemistry: The tumor cells are usually positive for vimentin, alpha-1 antitrypsin and alpha-1 antichymotrypsin. Our tumor was also focally SMA positive and focally weakly desmin positive. P 53 was expressed in 60% of the tumor cells, the proliferation marker Ki-67 was positive in 40% of the tumor cells. Our tumor lacked immunoreactivity for AFP, CEA, HepPar-1, CK8/18, CK7, myoglobin, myogenin, CD31, CD34, CD68, LCA, NSE, EMA and S-100.
Electron microscopy: Primitive mesenchymal cells with scant cytoplasmic organelles.
Cytogenetics: Complex with multiple gains and losses of different chromosomes.
Origin: Primitive mesenchymal cells. The theory of Mesenchymal hamartoma of the liver as a benign counterpart of undifferentiated embryonal sarcoma of liver still remains to be investigated. Three cases of MHL developing into UESL have been reported so far.
References: