Illinois Registry of Anatomic Pathology                                                          

Loyola/Hines

 

May 24, 2004

 

 

 

John M. Lee, M.D., Ph.D.

Helen M. and Raymond M. Galvin

Professor of Pathology, Pharmacology and Neuroscience,

Chairman, Department of Pathology

Loyola University Medical Center

Bruce E. Dunn, M.D.

Chief Pathologist

Veterans Integrated Service Network 12

Bruce.Dunn@med.va.gov

 

Jlee2@lumc.edu

 

 

 

Coordinated by

Maria M Picken, M.D., Ph.D.

Professor of Pathology and Medicine

Loyola University Medical Center

mpicken@lumc.edu

 

 

 

IRAP CASE #1

Presenter: Gulbeyaz Omeroglu M.D. (PGY2)

                    gomer@lumc.edu

Attending: John M. Lee, M.D., PhD

                   Jlee2@lumc.edu

                   Henry G. Brown M.D., PhD

                   hbrown@lumc.edu

 

DIAGNOSIS:

ATYPICAL TERATOID/RHABDOID TUMOR

 

CLINICAL HISTORY:

A seven-year old girl presented with intermittent vomiting, ataxia and loss of fine motor coordination. On neuroimaging a lobulated cystic mass was found at the cerebello-pontine angle involving the right posterior aspect of the fourth ventricle and extending into the right cerebellar hemisphere.

 

MICROSCOPIC FEATURES:

The diagnosis of an AT/RT requires nests or sheets of rhabdoid cells, which typically have eccentric round nuclei with a prominent nucleolus and an abundant eosinophilic cytoplasm. The nests of rhadoid cells may be adjacent to or surrounded by otherwise typical regions of primitive neuroectodermal tumor. Occasionally no primitive neuroectodermal cells are seen. The ratio of rhabdoid cells to primitive neuroectodermal cells may vary significantly. A unique feature of this embryonal tumor is the occurrence of an epithelial and /or mesenchymal component in addition to the rhabdoid cells.

 

IMMUNOHISTOCHEMISTRY:

Expression of EMA, Vimentin and SMA is characteristic of these tumors.

May also show expression of GFAP, Keratin, and Neurofilament protein.

They are uniformly negative for BHCG, PLAP, and AFP.

 

DIFFERENTIAL DIAGNOSIS:

MEDULLOBLASTOMA/LARGE CELL MEDULLOBLASTOMA

EPENDYMOMA

GERM CELL TUMOR

CHOROID PLEXUS CARCINOMA

ATYPICAL TERATOID/RHABDOID TUMOR

 

SPECIAL STUDIES:

Monosomy of chromosome 22

Deletion of chromosome 22q11.2

Mutations of INI1 gene

 

DIAGNOSTIC CONSENSUS:

If histological features and immunoassaying are consistent with AT/RT, the absence of an INI1 mutation is not sufficient to change diagnosis

The presence of an INI1 mutation in a tumor with features suggestive of medulloblastoma or primitive neuroectodermal tumor is sufficient to change the diagnosis to AT/RT.

 

 

 

 

 

EMA

SMA

SYN

VIM

GFAP

BHCG

AFP

       Cytogenetics

Medulloblastoma

 

   -

    -

   +

  

   +

 focal

     -

   -

Isochromosome 17

Ependymoma

 

focal

    -

    -

   +

    +

     -

   -

Complex abnormalities

Germ cell tumor

(v-variable)

   v

    v

   v

   v

     v

     +

   +

Gain of X,

Isochromosome 12p

Choroid plexus carcinoma

    -

    -

   -

   +

     -

     -

   -

Chromosome gains

7,9,12,15,17,18

AT/RT our case

    +

  +/-

    +

   +

focal

     -

   -

Deletion of 22q,

Gains of 8and 17

 

                                           

 

REFERENCES:

 

á Packer RJ, Biegel JA, Blaney S, Finley J, Geyer JR, Heidman R, Hilder J, Janss AJ, Kun L, Vezina G, Rorke Lb, Smith M: Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatric Hematol Oncol. 2002 Jun-Jul; 24 (5): 337-42

á Biegel JA, Kaplana G., Knudsen ES, Packer RJ, Roberts CWM, Thiele CJ, Weissman B, Smith M: The role of INI1 and the SWI/SNF Complex in the development of rhabdoid tumors: Meeting summary from the Workshop on Childhood Atypical Teratoid/Rhabdoid tumors. Cancer Research 62,323-328 January 1,2002

á Bambakidis NC, Robinson S, Cohen M, Cohen AR: Atypical teratoid/rhabdoid tumor of the central nervous system: clinical, radiographic and pathologic features. Pediatric Neurosurg.2002 Aug; 37 (2): 64-70

á Joanne M. Hilden, Jan Watterson, Darryl C. Longee, Christopher L. Moertel, Mary Elizabeth Dunn, Joanne Kurktzberg, Bernd W. Scheithauer: Central nervous system system atypical teratoid tumor/rhabdoid tumor: Response to intensive therapy and review of literature. Journal of  Neuroonc. 265-275, 1998

á Lutterbach J, Liegibel J, Koch D, Madlinger A, Frommhold H, Pagenstecher A: Atypical teratoid/rhabdoid tumors in adult patients: case report and review of the literature. J Neurooncol. 2001 March; 52(1): 49-56

á Paul Kleihues and Webster K. Cavenee: Tumors of the central Nervous System, World Health Organization Classification of Tumors

 

IRAP CASE #2

 

Presenter: Adam M. Quinn, D.O., PGY3

       aquinn1@lumc.edu

Attending:  Rasheed Hammadeh, M.D. 

                    rhamm@lumc.edu

 

Diagnosis:

Clear cell sarcoma of small bowel

 

CLINICAL HISTORY: 

A 21-year-old woman, with a childhood history of leukemia, presented to an outside hospital with dyspnea on exertion, dizziness and headaches for one month.  She was found to have severe iron deficiency anemia, heme positive stool and reported a thirty-pound weight loss over six months.  Initial endoscopic evaluations were unremarkable.  Capsule endoscopy revealed an area of ulceration in the small bowel, and CT of the abdomen and pelvis demonstrated thickening of the distal jejunum and proximal ileum with adjacent mesenteric lymphadenopathy.  The patient underwent exploratory laparotomy with partial resection of her small bowel.

 

GROSS FINDINGS: 

Intramural tumor with mucosal ulceration

Solid, grey white cut surface

Measuring 5.0 x 2.0 x 1.5 cm

 

MICROSCOPIC FINDINGS:

Most characteristic pattern consists of groups of cells divided by thin fibrous septa

Cytological features include vacuolated cytoplasm with vesicular nuclei and prominent nucleoli

3 of 24 lymph nodes positive for metastatic tumor

 

DIFFERENTIAL DIAGNOSIS:

¥Carcinoma

¥Neuroendocrine tumor

¥Gastrointestinal stromal tumor (GIST)

¥Melanoma

¥Tumor of neural origin (epitheliod MPNST and gangliocytic paraganglioma)

¥Clear cell sarcoma

 

IMMUNOHISTOCHEMICAL FINDINGS:

Positive:  S-100 (diffuse) and Vimentin (focal)

Negative:  Cytokeratin 20, Cytokeratin 7, Desmin, Leukocyte common antigen, Chromogranin, HMB 45, Melan-A, C-Kit (CD 117)

 

ANCILLARY STUDIES: 

Electron microscopy: No diagnostic organellae identified (i.e. neurosecretory granules, melanosomes, etc.)

FISH (interphase):  Rearrangement of EWS (22q12) observed in 14 of 50 nuclei examined

 

REFERENCES:

1.  Weiss SW and Goldblum JR.  Enzinger and Weiss' Soft Tissue Tumors. Mosby.  2001:1241-1250.

 2.  Ekfors TO, Kujari H, Isomaki M. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) in the duodenum: the first visceral case. Histopathology.  1993; 22:255-259.

 3.  Donner L, Trompler R, Dobin S. Clear cell sarcoma of the ileum. The crucial role of cytogenetics for the diagnosis. American Journal of surgical pathology.  1998; 22:121-124.

 4.  Fukuda T, Kakihara T, Baba K, et al. Clear cell sarcoma arising in the transverse colon. Pathology International.  2000; 50:412-416.

 5.  Pauwels P, Debiec-Richter M, Sciot R, Vlasveld T, den Butter B, Hegemeijer A, Hogendoorn PCW.  Clear cell sarcoma of the stomach.  Histopathology.  2002;41:526-530.

 6.  Fujimto M, Hiraga M, Kiyosawa T, et al. Complete remission of metastatic clear cell sarcoma with DAV chemotherapy.  Clinical and Experimental Dermatology.  2003; 28:22-24.




 






 


                                         IRAP CASE # 6

 

Presenter: Shahnaz Saeed, M.D. (PGY 3)

                   ssaeed@lumc.edu

Attending: Serhan Alkan, M.D. 

                   salkan@lumc.edu

 

DIAGNOSIS:

Splenic Marginal Zone Lymphoma With Circulating Villous Lymphocytes 

 

CLINICAL HISTORY:

68-year  old male with past medical history significant for glaucoma. Status-post cholecystectomy, appendectomy, hernia repair and throat surgery.

 

DIFFERENTIAL DIAGNOSIS:

á      CLL / SLL

á      Follicular lymphoma

á      Mantle cell lymphoma

á      Hairy cell leukemia

á      Lymphoplasmacytic lymphoma

á      Splenic marginal zone lymphoma.

 

KEY MOROPHOLOGIC FEATURES:

Splenic marginal cell lymphoma is characterized by marginal zone expansion. Marginal zone lymphocytes are small to medium size with abundant pale cytoplasm witch differentiates them from adjacent mantle zone (Bi-zonal effect or Margination). Peripheral blood with tumor cells with round nuclei, condensed chromatin and scant cytoplasm with polar lymphocytes with villous projections.

 

SPECIAL STUDIES:

á      Immunoglobulin heavy chain gene shows clonal rearrangement.

á      Flow cytometry shows these tumor cells are positive for CD45, CD19, CD20, with Lambda light chain restriction. These tumor cells are negative for CD5, CD10, CD11c, CD22, CD23, CD25, CD103 and FMC7.

 

CYTOGENETICS

á      Loss of 7q21-32 (CDK6 ), t (11 : 14) (cyclin D1)

 

TREATMENT:

á      Splenectomy

á      Chemotherapy

á       Recent report indicated regression of Splenic marginal zone lymphoma after antiviral treatment of hepatitis C virus infection, in hepatitis C positive patients

 

 

 DISCUSSION:

Splenic marginal zone lymphoma (SMZL) is a recently described B-cell lymphoma with distinct clinical, morphologic, and immunophenotypic findings. SMZL has been included as a provisional entity in the Revised European-American Classification of Lymphoid NeoplasmÕs (REAL). Patients with this disease are typically elderly men with splenomegaly who present with disseminated disease at the time of diagnosis. Peripheral lymphocytosis and a low level of monoclonal serum paraprotein (usually immunoglobulin M) could be demonstrated in greater 50% of patients. Splenic histology usually shows  infiltration of white pulp disease with a marginal zone involvement ;however, to some degree of red pulp infiltration may be seen. The neoplastic cells are B cells (CD20 positive) and, in nearly all cases, lack co expression of CD5, CD10, and CD43. No consistent chromosomal alteration has been identified. In general, the prognosis is favorable and the disease is indolent, with a reported survival rate of 78% at 5 years.2

 A study showing regression of splenic lymphoma with villous lymphocytes after antiviral treatment of Hepatitis C virus infection, was published in N Engl J Med.2002 Jul 11: 347 (2): 89-94.This resembles to the finding that H-pylori infection has a pathogenic role in gastric lymphoma involving mucosa associated lymphoid tissue. As is the case in patients with Splenic marginal zone lymphoma, undergo complete remission and loss of detectable Hepatitis C RNA after antiviral treatment, suggesting the role of hepatitis C virus in the pathogenesis of splenic marginal zone lymphoma.

 

 

REFERENCES: