Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
Case # 1
Presenter: Jennifer Dettloff MD
Attending: Ira Miller MD, PhD

Diagnosis: Anaplastic large cell lymphoma, ALK negative, of the spleen
Important Differential Diagnosis
Neoplasm
Typical Morphology
Usual Site
Immunophenotype

Histiocytic
sarcoma
Noncohesive oval cells with
oval, folded nuclei
Extranodal
CD68, CD163,
Lysozyme

Indeterminate
dendritic cell
tumor
Spindled to ovoid cells with
eosinophillic cytoplasm and
nuclear grooves
Dermal
S100, CD1a

Interdigitating
dendritic cell
sarcoma
Spindled cells in a storiform
pattern with ample
eosinophillic cytoplasm
LN
S100, vimentin,
weak CD68

Langerhans’
histiocytosis
Oval grooved nuclei with fine
chromatin, intermixed mixed
cells including eosinophils
Bone
CD1a, langerin,
S100

Follicular
dendritic cell
sarcoma
Spindled cells in a storiform/
whorled pattern with moderate
eosinophillic cytoplasm
LN
CD21, CD23,
CD35

Fibroblastic
reticular cell
tumor
Similar to dendritc neoplasms
but with intermixed collagen
fibrils
LN, spleen
Cytokeratins, MSA

T cell/histiocyterich DLCL
Large B cells embedded in a
background of variable
amounts of small T cells and
histiocytes
LN
Large cells express
pan B cell markers

ALCL
Large often pleomorphic cells,
hallmark cells
LN
CD30 (membrane
and golgi) +/- ALK

Classical
Hodgkin’s
lymphoma
RS cells, rich inflammatory
background
LN
CD30, CD15,
PAX5
Key morphological and immunohistochemical features of this case:
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
The tumor cells had ample eosinophillic textured cytoplasm and nuclei with open
chromatin and nuclear indentations/ grooves. There was little pleomorphism and very
rare mitotic figures.
Immunohistochemical stains for CD30, EMA are positive in the tumor cells. The tumor
cells were negative for pan B cell markers, histiocytic/ Langerhans cell markers, as well
as the nearly all T cell markers.
Discussion:
• Anaplastic large cell lymphoma usually involves lymph nodes, in up to 60% of
the cases there is extranodal involvement but primary splenic ALCL is rare.
• Our case has an unusual histiocytoid morphology.
• Our patient was 30, younger than the typical age for an ALK negative ALCL. The
mean age for an ALK negative ALCL lymphoma is 40-65 (higher than ALK
positive).
References:
Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., Thiele J.,
Vardiman J.W. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues
IARC: Lyon 2008
Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, Diehl V: Production of
a monoclonal antibody specific for Hogkin and Sternberg-Reed Cells of Hodgkin’s
Disease and a subset of normal lymphoid cells. Nature 299;65, 1982
H Stein, DY Mason, J Gerdes, N O’Connor, J Wainscoat, G Pallesen, K Gatter, B Falini,
G Delsol, H Lemke, R Schwarting and K Lennert: The expression of the Hodgkin’s
disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that
Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid
cells. Blood 66:848-858, 1985
Ferreri A, Govi S, Pileri S, Savage K: Anaplastic large cell lymphoma, ALK-negative.
Critical reviews in Oncology/ Hematology, 2012
Case # 2
Presenter: Rohit Singh MD
Attending: Jerome Loew MD

Diagnosis: Spleen and splenic hilar lymph node with diffuse large B-cell
lymphoma non-germinal center type with diffuse red pulp infiltration.
Important Differential Diagnosis of this case:
• Plasmablastic lymphoma.
• Intravascular lymphoma.
•
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
Anaplastic large cell lymphoma.
Key features
Clinical: Massive splenomegaly with multiple nodules. No systemic (bone marrow and
liver involvement).
Morphologic: Discrete nodules in spleen.
Histological: Diffuse red pulp infiltration (splenic cords) with large B-cell lymphoma
with splenic lymph node involvement. CD20 negative, Pax-5 positive, CD30 positive,
CD138 negative, CD3 negative, CD5 negative
Discussion:
• Primary splenic DLBCL rare.
• Nodules of varied size; involves white pulp.
• 24 cases of DLBCL diffusely infiltrating splenic red pulp without discrete tumor
masses (DLBCLRP) reported so far.
• Very poor prognosis.
• This case raises the question of whether DLBCL manifesting as diffuse
infiltration of the splenic red pulp (DLBCLRP) is truly a separate entity or a part
of a spectrum with overlapping features.
• No study has probed this question.
• Rush experience: none of our other cases had diffuse red pulp involvement.
References:
• Kuratsune H, Machii T, Aozasa K et al (1988) B cell lymphoma showing
clinicopathological features of malignant histiocytosis. Acta Haematol 79:94–98
• Faravelli A, Gambini S, Perego D et al (1995) Splenic lymphoma: unusual case
with exclusive red pulp involvement. Pathologica 87:692–695
• Kobrich U, Falk S, Karhoff M et al (1992) Primary large cell lymphoma of the
splenic sinuses: a variant of angiotrophic B-cell lymphoma (neoplastic
angioendotheliomatosis)? Hum Pathol 23:1184–1187
• Kroft SH, Howard MS, Picker LJ et al (2000) De novo CD5+ diffuse large B-cell
lymphomas. A heterogeneous group containing an unusual form of splenic
lymphoma. Am J Clin Pathol 114:523–533
• Mollejo M, Algara P, Mateo MS et al (2003) Large B-cell lymphoma presenting
in the spleen: identification of different clinicopathologic conditions. Am J Surg
Pathol 27:895–902
• Morice WG, Rodriguez FJ, Hoyer JD et al (2005) Diffuse large B cell lymphoma
with distinctive patterns of splenic and bone marrow involvement:
clinicopathologic features of two cases. Mod Pathol 18:495–502
• Palutke M, Eisenberg L, Narang S et al (1988) B lymphocytic lymphoma (large
cell) of possible splenic marginal zone origin presenting with prominent
splenomegaly and unusual cordal red pulp distribution. Cancer 62:593–600
• WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th Ed.
2008
•
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
Kashimura M, Noro M, Akikusa B, et al.Primary splenic diffuse large B-cell
lymphoma manifesting in red pulp. Virchows Arch (2008) 453:501–509
Case # 3
Presenter: Richa Jain MD
Attending: Shriram Jakate MD, FRCPath

Diagnosis: Fulminant hepatic necrosis with rapid disease progression in
autoimmune hepatitis with cirrhosis.
Important Differential Diagnosis of Fulminant hepatic necrosis in previously
cirrhotic liver
 Progression of primary disease itself
 Superadded viral hepatitis or other infections
 Superadded drug hepatotoxicity (including alcohol and herbal formulations)
 Superadded hypoxic hepatitis
Key distinguishing features:
All superadded causes should be ruled out clinically and by performing appropriate
laboratory investigations.
Discussion:
 Autoimmune hepatitis is an immune-mediated inflammation of the liver.
 The diagnosis requires correlation of:
-laboratory abnormalities (elevation of AST, ALT>>elevation of ALP),
-serology (elevated titers of ANA/ASMA/Anti-LKM antibodies and
elevated IgG) and
-liver histology (interface hepatitis with predominance of plasma cells,
hepatocyte rosettes, intrasinusoidal lymphocytosis).
 Usual age of onset: 4th-5th decade.
 Presentations: acute, chronic, cirrhosis, fulminant hepatitis
 It is crucial to make the diagnosis as the response to prednisone therapy is
dramatic and often saves life of the patient.
References:
1. Alvarez F, Berg PA, Bianchi FB et al. International autoimmune hepatitis group report:
Review of criteria for diagnosis of autoimmune hepatitis. Journal of Hepatology
1999;31:929-938.
2. Czaja AJ. Acute and acute severe (fulminant) autoimmune hepatitis. Dig Dis Sci. 2012.
DOI 10.1007/s10620-012-2445-4
3. Henrion J. Hypoxic hepatitis. Liver international. 2011. DOI: 10.1111/j.14783231.2011.02655.x
4. Invernizzi P, Mackay IR. Autoimmune pediatric liver disease. World J Gastroemterol
2008;14:3360-3367.
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
5. Manns MP, Czaja AJ, Gorham JD et al. Diagnosis and management of autoimmune
hepatitis. AASLD practice guidelines.
http://www.aasld.org/practiceguidelines/Documents/AIH2010.pdf
6. Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children: What is different from
adult AIH? Semin Liver Dis 2009;29:297-306.
7. Misdraji J, Thiim M, Graeme-Cook FM. Autoimmune hepatitis with centrilobular
necrosis. Am J Surg Pathol 2004;28:471-478.
8. Stravitz RT, Lefkowitch JH, Fontana RJ et al. Autoimmune acute liver failure:
Proposed clinical and histological criteria. Hepatology 2011;53:517-526.
Case # 4
Presenter: Jon Gates MD
Attending: Paolo Gattuso MD

Diagnosis: Ectopic sphenoid sinus pituitary adenoma
Important Differential Diagnosis of ectopic sphenoid sinus pituitary adenoma
 paraganglioma
 esthesioneuroblastoma
 carcinoid tumor
 Ewing sarcoma/PNET
 Mucosal melanoma
Key histological features: Submucosal neoplasm composed of uniform cells with
abundant granular, partially vacuolated cytoplasm uniform nuclei with a neuroendocrine
chromatin pattern and occasional nuclieoli. The mucosal lining cells are ciliated,
columnar epithelium.
Key immunohistochemical features:
Neoplasm is positive for synaptophysin, chromogranin, CD56, and CK8/18. Reticulin
stain shows an incomplete reticulin framework. The neoplasm is negative for S-100 and
pituitary hormone markers.
Key clinical features:
Two month history of rhinorrhea and headache. Radiographic findings of a cystic
neoplasm in the right sphenoid sinus as well as intact sella turcica with non-displaced,
normal in size pituitary gland. Surgical findings of an intact sella turcica.
Discussion:Ectopic sphenoid sinus pituitary adenomas are defined as pituitary gland
neoplasms occurring separate from, and without involvement of, the sella turcica (i.e.
with normal anterior pituitary gland). Ectopic sphenoid sinus pituitary adenomas result
from aberrations in the embryologic development of the anterior pituitary and are benign
tumors with no metastatic potential. They may be fully functional, hormone secreting
tumors resulting in endocrine disorders. Although these are rare neoplasms, they are an
important part of the differential diagnosis for sphenoid sinus tumors as it is important to
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
identify this benign tumor in order to avoid the significant morbidity associated with
treatments employed for several of the other tumors in the differential diagnosis
References:
Ectopic Sphenoid Sinus Pituitary Adenoma (ESSPA) with Normal Anterior Pituitary
Gland: A Clinicopathologic and Immunophenotypic Study of 32 Cases with a
Comprehensive Review of English Literature, L Thompson, R Seethala, S Muller. Head
and Neck Pathology (2012) 6:75-100
Differential Diagnosis in Surgical Pathology. P Gattuso, et al. Saunders, 2010
(Philadelphia).
Case # 5
Presenter: Matthew Fox MD
Attending: Ritu Ghai MD
Diagnosis: Primary PEComa of adrenal gland
Important Differential Diagnosis:
• Adrenal cortical carcinoma
• Ganglioneuroma
• Melanoma
• Clear cell carcinoma
• Conventional clear cell sarcoma (malignant melanoma of soft parts)
• Leiomyosarcoma
• Gastrointestinal stromal tumor
Key features:
• Family of tumors characterized by:
• Epithelioid and spindle cells with clear to granular eosinophilic cytoplasm radially
arranged around vessels
• Smooth muscle and melanocyte markers
• Deletions in TSC1/TSC2 and activation of mTOR
Discussion:
• Rare tumor with putative perivascular cell differentiation composed of clear
epithelioid cells with coexpression of smooth muscle and melanocytic markers.
(“myomelanocytes”)
• The perivascular epithelioid cell tumor (PEComa) family includes
• Angiomyolipoma
• Lymphangioleiomyoma and lymphangioleiomyomatosis
• Clear-cell “sugar” tumor of lung
•
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
Other rare tumors of visceral, soft tissue, bone origin
References:
Folpe, AL & Kwiatkowski DJ. Perivascular epithelioid cell neoplasms: pathology and
pathogenesis.Human Pathology 2010; 41: 1-15
Greene, LA et al. Recurrent perivascular epithelioid cell tumor of the uterus (PEComa):
an immunohistochemical study and review of the literature.
Gynecologic Oncology 2003; 90: 677-681.
Weiming, Yu et al. M C-Kit–positive metastatic malignant pigmented clear-cell
epithelioid tumor arising from the kidney in a child without tuberous sclerosis
Annals of diagnostic pathology 2005; 9; 6: 330-334.
Case # 6
Presenter: Lin Cheng, M.D. Ph.D.
Attending: David Cimbaluk, M.D.
Diagnosis:
 IgA dominant postinfectious glomerulonephritis
 Diabetic glomerulosclerosis
 Severe arteriolar hyalinosis
 Acute tubular injury with regeneration
Important Differential Diagnosis of IgA dominant postinfectious glomerulonephritis
 IgA nephropathy
Key features of IgA dominant postinfectious glomerulonephritis:
 Clinical features:
o Intercurrent culture-documented staphylococcal infection
o Hypocomplementemia
o Presentation in older age
o History of diabetes mellitus
o Acute renal failure at presentation
 Pathologic features:
o Endocapillary proliferation with neutrophil infiltration on LM
o Stronger staining for C3 than IgA on IF
o “Starry sky” pattern on IF
o Subepithelial “humps” on EM
Discussion:
IgA-dominant postinfectious glomerulonephritis is an increasingly recognized
morphologic variant of postinfectious glomerulonephritis. First reported in 2003, a total
of 49 cases have since been reported in the English literature. The vast majority of cases
occur in association with staphylococcal infections. Diabetes is a major risk factor, likely
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
reflecting the high prevalence of staphylococcal infection in diabetics. Patients typically
present with severe renal failure, proteinuria and hematuria. Histologically, most cases
exhibit endocapillary hypercellularity and neutrophil infiltration. IgA-dominant
postinfectious glomerulonephritis differs from the classic postinfectious
glomerulonephritis in that the latter has glomerular deposition of C3 and IgG on
immunofluorescence. However, the IgA-dominant postinfectious glomerulonephritis has
IgA as the dominant or co-dominant immunoglobulin. This variant of postinfectious
glomerulonephritis must be distinguished from IgA nephropathy. Features that favor
IgA-dominant postinfectious glomerulonephritis over IgA nephropathy are listed
above. Although IgA-dominant postinfectious glomerulonephritis appears to be a oneshot disease (without the recurrences and exacerbations that characterize primary IgA
nephropathy), prognosis is guarded with less than a fifth of patients fully recovering renal
function. Future studies directed to pathogenesis may help to identify the nephritogenic
staphylococcal antigen(s) and the immunologic basis for the dominant IgA host
response.
References:
 Nasr SH, Markowitz GS, Whelan JD, Albanese JJ, Rosen RM, Fein DA, Kim SS,
D’Agati VD: IgA-dominant acute poststaphylococcal glomerulonephritis
complicating diabetic nephropathy. Hum Pathol 2003;34:1235–1241.
 Haas M, Racusen LC, Bagnasco SM: IgAdominant postinfectious
glomerulonephritis: a report of 13 cases with common ultrastructural features.
Hum Pathol 2008; 39:1309–1316
 Nasr SH, D'Agati VD. IgA-dominant postinfectious glomerulonephritis: a new
twist on an old disease. Nephron Clin Pract. 2011;119(1):c18-25; discussion c26.
doi: 10.1159/000324180. Epub 2011 Jun 9
Case # 7
Presenter: Matthew Stemm MD
Attending: Brett Mahon
 Diagnosis: Dedifferentiated Chondrosarcoma
Important Differential Diagnosis of Dedifferentiated Chondrosarcoma
 Mesenchymal chondrosarcoma
 Osteosarcoma (if there is bone formation)
 Collision tumor/Metastasis of chondrosarcoma and spindle cell lesion
Key points:
 Usually affects patients over 50
 Most commonly occurs in long bones
 Composed of two divergent histologies
o Low-grade cartilaginous component
o High-grade noncartilaginous sarcomatous component
 Highly lethal
Illinois Registry of Anatomic Pathology
November 19, 2012
Rush University Medical Center
o Generally the dedifferentiated component is resistant to chemotherapy and
radiation therapy
o Five year survival <10%
Discussion: Although Dedifferentiated Chondrosarcoma is defined by having a high
grade dedifferentiated component, cases are now being reported with low grade
morphology. Early data suggests that prognosis may be improved, though data is too
limited for statistical analysis.
References:
Franchi A, Baroni G, Sardi I, Giunti L, Capanna R, Campanacci D. Dedifferentiated peripheral chondrosarcoma: a
clinicopathologic, immunohistochemical, and molecular analysis of four cases. Virchows Arch. 2012 Mar;460(3):33542. Epub 2012 Feb 16.
Bai S, Wang D, Klein MJ, Siegal GP. Characterization of CXCR4 expression in chondrosarcoma of bone. Arch Pathol
Lab Med. 2011 Jun;135(6):753-8.
Kim MJ, Cho KJ, Ayala AG, Ro JY. Chondrosarcoma: with updates on molecular genetics. Sarcoma.
2011;2011:405437. Epub 2011 Feb 15.
Tang X, Lu X, Guo W, Ren T, Zhao H, Zhao F, Tang G. Different expression of Sox9 and Runx2 between
chondrosarcoma and dedifferentiated chondrosarcoma cell line. Eur J Cancer Prev. 2010 Nov;19(6):466-71.
Dornauer K, Söder S, Inwards CY, Bovee JV, Aigner T. Matrix biochemistry and cell biology of dedifferentiated
chondrosarcomas. Pathol Int. 2010 May;60(5):365-72.
Rozeman LB, de Bruijn IH, Bacchini P, Staals EL, Bertoni F, Bovée JV, Hogendoorn PC. Dedifferentiated peripheral
chondrosarcomas: regulation of EXT-downstream molecules and differentiation-related genes. Mod Pathol. 2009
Nov;22(11):1489-98. Epub 2009 Sep 4.
MR Hameed, J Healey, C Morris, P Boland, MJ Klein. Dedifferentiated Chondrosarcoma with Low Grade
Dedifferentiated Component – A Single Instituitional Study. Modern Pathology 24 [Sup1]15A, 2011