Illinois Registry of Anatomic Pathology
April 22, 2013
Loyola University Medical Center
Case #1
Presenter: Zulfia McCroskey.
Attendings: Xiuzhen Duan, M.D., Ph.D.
Clinical History: The patient is a 24-year-old female, G2P2. Her forst two pregnancies were uncomlicated. She was
presented to OSH for abnormal uterine bleeding; elevated serum beta-hCG (120 mIU/ml) and underwent D&C for a
suspected missed abortion in 2009. Slides were not available for review. In 2010 she presented again with abnormal
uterine bleeding and elevated serum beta-hCG (120 mIU/ml). MRI demonstated a large heterogeneous enhancing mass
containing both cystic and solid components in the posterior fundal and uterine body, extending into the cervix.
Hysterectomy was performed.
Diagnosis: Placental site trophoblastic tumor
Differential Diagnosis:
Trophoblast derivatives:
 Choriocarcinoma
 Epithelioid trophoblastic tumor
 Placental site trophoblastic tumor
 Exaggerated placental site
 Placental site nodule
Other non-trophoblastic malignancies:
 Poorly differentiated squamous cells carcinoma
 Epithelioid leiomyosarcoma
Key Morphologic Features:
Gross: Endophytic, poorly circumscribed mass, involving the full thickness posterior uterine wall, ill defined,
solid, with areas of necrosis and hemorrhage.
Microscopic: Tumor grows by splitting apart myometrium fibers rather than destructing them. Absence of
biphasic pattern, absence of extensive hemorrhagic necrosis, most of the tumor cells are mononuclear.Tumor
cells invade and replace blood vessel walls.
Immunohistochemistry and Special Stains:
Positive: Ki67, mean15%, hCG weak and focal.
Discussion:
Prevalence and Clinical Presentation
Rare malignancy, approximately 100 cases have been reported in the English literature *
Typically occur in the reproductive group, mean 32 years
Enlarged uterus, amenorrhea and elevated β-hCG can mislead to a diagnosis of normal pregnancy
Biological behavior is difficult to predict: 30% of PSTT metastatic at the time of presentation and 50% fatal
PSTT responds poorly to chemo- and radiation therapy (comparing to Choriocarcinoma)
History of preceding normal pregnancy, abortion or a complete mole within a median time interval of 18 months
common, the longest time interval is 18 years
Adverse prognostic factors:
Clinical:
Age >35 years, interval since last pregnancy >2 years, previous term birth, high beta-hCG (>1000mIU/ml)
Histological:
Deep myometrium invasion, necrosis, increased mitoses
References:
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Neda Kalhor et al.Immunohistochemical Studies of Trophoblastic Tumors. Am J Surg Pathol; 2009 33 (4):633-638
Gillespie et al. Placental Site Trophoblastic Tumour: a Rare but Potentially Curable Cancer. British Journal of Cancer 2000;82(6): 1186–
1190
M Bower,FJ Paradinas,RA Fisher,et al. Placental site trophoblastic tumor: molecular analysis and clinical experience. Clin Cancer Res
1996;2:897-902
IT Yeh, DM O’Connor, RJ Kurman. Intermediate trophoblast: further immunocytochemical characterization.Mod Pathol.1990 May;3(3):282-7.
E D'Angelo, J Prat. Uterine sarcomas: A review. Gynecol Oncol 2009, doi:10.1016/j. ygyno.2009.09.023
SJ Robboy et al. Pathology of the Female Reproductive tract. 2002:769-779
Case #2
Presenter: Mohanad Shaar, MD
Attendings: Sherri Yong, MD; Stefan Pambuccian, MD, PhD
A 30-year-old female with hystery of cerebral palsy and developmental delay presented to
Loyola with an unexplained, progressively elevated alkaline phosphatase levels (222 ) over the past two years
and a recently recently found right liver mass on an OSH ultrasound. OSH Ct scan showed a 9.0 mass with
irregular vascular enhancement. Percutaneous biopsy was performed. A diagnosis was made and the patient
underwent partial hepatectomy.
Clinical history:
Diagnosis: Inflammatory/telangiectatic Hepatocellular Adenoma
Differential Diagnosis:
• Well-differentiated Hepatocellular Carcinoma
• Fibrolamellar variant of Hepatocellular carcinoma
• Focal Nodular Hyperplasia
Key Morphologic Features:
Histologic examination reveals absence of well-defined portal tracts. However, presence of portal-like spaces
constaining thickened, dystrophic vessels with surrounding ductular reactions is the main feature. Variable inflammatory
infiltrates can be seen predominantly around the thickened vessels, in addition to areas of sinusoidal dilatation and
peliosis. Hepatocytes do not show cytologic or architectural atypia. No rosette or acinar formation is present.
Immunohistochemistry and Special Stains:
No stainable iron is identified on iron stain. Trichrome stain shows no significant fibrosis or fibrous septae but highlights
the thick-walled blood vessels. Immunoperoxidase stains show absence of beta catenin nuclear staining,
endothelialization of sinusoids (CD34+), and rare, small CD19 + bile ductules. Serum Amyloid A (SAA) is strongly
positive only in the mass hepatocytes.
Discussion:
- Rare, strongly associated with OCPs.
- No well-understood outlines on when or which cases need to be treated.
- Diagnosis on core biopsy is a big challenge.
- Introduction of the new genotype/phenotype classification of HCAs:
1. HNF1A mutated HCA
2. B-catenin mutated HCA
3. Inflammatory/Telangiectatic HCA
4. Non-mutated HCA
- The new classification provides clinicians with more accurate cut offs in terms of management, and also allows
pathologists to better apply IHC studies in order to make such a diagnosis on core biopsy.
References:
Paulette Bioulac-Sage et al. Immunohistochemical Markers on Needle Biopsies Are Helpful for the Diagnosis of Focal Nodular Hyperplasia and
Hepatocellular Adenoma Subtypes; Am J Surg Pathol Volume 36, Number 11, November 2012
Nafis Shafizadeh et al. Diagnosis of Well-differentiated Hepatocellular Lesions: Role of Immunohistochemistry and Other ancillary techniques; Adv
Anat Pathol, volume 18, November 2011
V. Paradis: Benign Liver Tumors, An Update; Clin Liver Dis 14 (2010)
Wanless IR, Albrecht S, Bilbao J. Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and
neoplasia of the brain; Mod Pathol 1989;2:456–62
Bioulac-Sage P, Rebouissou S, Sa Cunha A, et al. Clinical morphologic, and molecular features defining so-called telangiectatic focal nodular
hyperplasias of the liver; Gastroenterology 2005;128:1211–8
Zucman-Rossi J, Jeannot E, Van Nhieu JT, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship
with HCC; Hepatology 2006;43:515–24
P. Bioulac-Sage, H. Laumonier, G. Couchy et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience;
Hepatology, vol. 50, no. 2, pp. 481–489, 2009.
Paulette Bioulac-Sage et al. Value and Limits of Routine Histology Alone or Combined with Glutamine Synthetase Immunostaining in the Diagnosis
of Hepatocellular Adenoma Subtypes on Surgical Specimens; International Journal of Hepatology, Volume 2013
Bioulac-Sage P, Rebouissou S, Thomas C, et al. Hepatocellular adenoma subtype classification using molecular markers and
immunohistochemistry; Hepatology 2007;46:740–8.
Alten et al: Management of Hepatocellular Adenoma; Liver International (2012)
Case #3
Presenter: Sameer Al Diffalha, M.D.
Attendings: Kelli Ann Hutchens, M.D
Clinical history: A 48-year-old man presented on 8/10/12 to the clinic for evaluation of a non-painful right gluteal mass.
He noted this mass about 6 months ago. He did not recall any changes in the mass. MRI (outside report on 8/6/2012)
showed a (3.4 x 1.8 x 2.9) cm irregularly enhancing soft tissue mass in the right buttock which extends into the adjacent
gluteus maximus muscle. The patient had wide radical excision of his right gluteal mass.
Diagnosis: Dermatofibrosarcoma Protuberans, Myxoid variant.
Differential Diagnosis:
 Cellular myxoma
 Superficial angiomyxoma
 Myxofibrosarcoma
 Low grade fibromyxoid sarcoma
 Myxoid neurofibroma
 Myxoid liposarcoma
 Myxoid nerve sheath tumor
Key Morphologic Features:
Gross: Well-circumscribed mass with gelatenous cut surfcase. No heorrhehage or necrosis were seen.
Microscopic: The tumor is composed of spindle cells without atypia in a myxoid stroma. There is a focal area
where the neoplasm is tracking through the adipose tissue and touches the margin. Few lipoblast like cells were
seen.Very rare mitotic figures were noted. Increased numbers of capillaries are identified without arborizing
feature.
Immunohistochemistry and Special Stains:
Positive: The neoplastic spindle cells are extensively positive for CD34.
Negative: They are negative for SMA and S100.
Discussion:
 The first case of myxoid DFSP was described in 1983. [2] It is a rare variant of DFSP, less than 50 cases have
been described in the literature with 2 significant series reported.
 It has Infiltrative growth pattern into the underlying subcutaneous fat. The tumor lacks the storiform growth
pattern secondary to the prominent myxoid stroma (The majority of cases have focal areas of classic DFSP with
the characteristic tight storiform pattern). [1]
 Cytogenetically, all forms of DFSP are characterized by t (17; 22) (q22; q13) translocation. This translocation
fuses the collagen type I alpha 1 gene from chromosome 17q22 to the platelet-derived growth factor ß-chain
gene from chromosome 22q13, forming a chimeric COL1A1-PDGFB gene.[1]
 Behaves in a manner similar to conventional DFSP.[3]
 Surgical excision remains the mainstay of treatment for dermatofibrosarcoma protuberans by Mohs surgery or
wide excision.[4]
References:
[1]: Thomas Mentzel, MD, et al “Myxoid Dermatofibrosarcoma Protuberans: Clinicopathologic, Immunohistochemical, and Molecular
Analysis of Eight Cases” Am J Dermatopathol 2007; 29:443–448.
[2]: M. Campos et al. “Myxoid Dermatofibrosarcoma Protuberans in Childhood” Actas Dermosifiliogr. 2012; 103(5):422---426.
[3]: Julie D.R. Reimann,, MD PhD et al.” Myxoid Dermatofibrosarcoma Protuberans: A Rare Variant Analyzed in a Series of 23 Cases”
Am J Surg Pathol 2007; 31:1371–1377
[4]: McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol. Apr 2004; 31(2 Suppl 6):30-6.
[5]: Serra-Guillén C, et al. Dermatofibrosarcoma Protuberans. Actas Dermosifiliogr. 2012; 103:762-77.
[6]: Han A, Chen EH, Niedt G, Sherman W, Ratner D. Neoadjuvant imatinib therapy for dermatofibrosarcoma protuberans. Arch
Dermatol. Jul 2009;145(7):792-6
Case #4:
Presenter: Reeba A. Omman, MD
Attending: Güliz A. Barkan, MD
Clinical History: A 58-year-old man with a history of spinal cervical fusion, presented to his physician with a sharp left
back pain lasting 3 weeks, following a traumatic injury. A CT (with contrast) was revealed a 1.5 cm mass in the
pancreatic body, confirmed by MRI. The patient then underwent an endoscopic ultrasound guided Fine Needle
Aspiration of this mass. Images submitted are from the Fine Needle Aspiration of the mass lesion.
Diagnosis: Solid-pseudopapillary neoplasm (clear-cell variant)
Differential Diagnosis:
1. Pancreatic Ductal Adenocarcinoma, vacuolated pattern
2. Signet Ring Cell Carcinoma
3. Metastatic Carcinomas (RCC clear cell type, Urothelial Carcinoma, etc.)
4. Perivascular Epithelioid Cell Tumor (PEComa)
5. Pancreatic Neuroendocrine Tumor, clear cell variant
Key Morphologic Diagnosis:
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Gross: Large, round, solitary mass (range: 3-18 cm), which is soft and fluctuant. They are usually encapsulated
and well demarcated from the surrounding pancreas. The cut surfaces reveal a lobulated, soft, tan-brown to
yellow mass. The mass is often associated with cystic degeneration, necrosis and hemorrhagic especially when
large.
Microscopic: Cytology: High cellularity, papillary-like structures with thin fibrovascular cores, loosely cohesive
aggregates, rosettes, single cells and stripped nuclei. Few cells with cytoplasmic vacuolization. Bland,
plasmacytoid, round to oval nuclei, with finely granular chromatin and small indistinct nucleoli. Nuclear
indentations and grooves. In the clear cell variant more than 90% of tumor cells have cytoplasmic vacuolation.
Due to cytoplasmic rupturing the vacuoles can be seen also in the background. Histology: Sheets of uniform,
polygonal cells arranged around numerous delicate capillary-sized blood vessels, and focal agrregates of cells
forming solid areas. Calcification and ossification may ne seen. The neoplastic cells have either eosinophilic or
clear vacuolar cytoplasm. Occasionally they contain eosinophilic, diastase-resistant PAS-positive hyalin
globules. Mitotic figures are rare. Typically there is a lack of desmoplastic reaction. In the clear cell variant
cytoplasmic vacuoles are observed which in electron microscopy showed to be dilated mitochondria and smooth
endoplasmic reticulum.
Immunohistochemistry and Special Stains:
Positive: B-catenin (nuclear), CD10, progesterone receptor, vimentin, alpha-1 antitrypsin, alpha-1
antichymotrypsin, amylase, galectin-3, synaptophysin (variable), FLI-1, CD56
Negative: E-cadherin (membranous), pancytokeratin, melan-A, chromogranin, mucicarmine, PAS, and Oil-Red-O
Discussion:
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Low-grade malignant epithelial neoplasm of the exocrine pancreas
Comprises 1-2% of all pancreatic malignancies, overall mortality rate is around 1.5%
Occurs primarily in women in their twenties; most commonly located in the tail of the pancreas
Size is approximately 4 cm on average, well demarcated, encapsulated
Clear cell variant: First described by Albores-Saavedra et al. in 2006
Trabecular and solid growth of multivacuolated clear cells with more than 90% of tumor cells. Pseudopapillary
pattern typically not observed. Cytoplasmic vacuoles do not stain for glycogen, mucin or lipid since they are
dilated mitochondria and smooth endoplasmic reticulum.
References:
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Albores-Saavedra J, Simpson KW, Bilello SJ. The clear cell variant of solid pseudopapillary tumor of the pancreas: a previously unrecognized pancreatic neoplasm. Am J Surg Pathol. 2006
Oct;30(10):1237-42.
Chen S., Wu H. H. and Cramer H. “Fine needle aspiration cytology of a clear cell (lipid-rich) pancreatic neuroendocrine tumour in a patient without von Hippel-Lindau disease.” Blackwell
Publishing Ltd. Cytopathology. 2012. doi: 10.1111/j.1365-2303.2012.00975.x
Cibas E .S. and Ducatman B. S. Cytology: Diagnostic Principles and Clinical Correlates. 3rd. ed. Elsevier and Saunders. 2009.
Dursun N, Feng J, Basturk O, Bandyopadhyay S, Cheng JD, Adsay VN. Vacuolated cell pattern of pancreatobiliary adenocarcinoma: a clinicopathological analysis of 24 cases of a poorly
recognized distinctive morphologic variant important in the differential diagnosis. Virchows Arch. 2010 Dec;457(6):643-9. doi: 10.1007/s00428-010-0978-5. Epub 2010 Oct 8.
El-Bahrawy MA, Rowan A, Horncastle D, Tomlinson I, Theis BA, Russell RC, Stamp G. E-cadherin/catenin complex status in solid pseudopapillary tumor of the pancreas. Am J Surg Pathol. 2008
Jan;32(1):1-7.
Hruban R. H., Pitman M. and Klimstra D. Tumors of the Pancreas. AFIP Atlas of Tumor Pathology Series 4. ARP Press. 2007.
Kaur G, Bakshi P, Verma K. Fine needle aspiration cytology of metastatic urothelial carcinoma: Study of seven cases with review of literature. J Cytol. 2012 Apr;29(2):116-20. doi: 10.4103/09709371.97151.
Rapkiewicz A, Gorokhovsky R, Farcon E, Das K. Cytology of metastatic prostate cancer following orchiectomy and antiandrogen therapy: a diagnostic challenge. Diagn Cytopathol. 2008
Jul;36(7):499-502. doi: 10.1002/dc.20814.
Tanino M, Kohsaka S, Kimura T, Tabu K, Nishihara H, Sawa H, Kawami H, Kamada H, Shimizu M, Tanaka S. A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult
male patient. Ann Diagn Pathol. 2012 Apr;16(2):134-40. doi: 10.1016/j.anndiagpath.2010.11.011. Epub 2011 Mar 10.
Zhao et . al. “Solid-pseudopapillary neoplasm of the pancreas: awareness of unusual clinical presentations and morphology of the clear cell variant can prevent diagnostic errors.” Diagnostic
Cytopathology. 14 Aug 2012.
Case #5
Presenter: Payal Sojitra, M.D.
Attending: Ameet R. Kini, M.D., PhD.
Clinical history: An 18-year-old male presented with a left lower leg violaceous bruise-like lesion showing a
large central superficial erosion. A CBC showed WBC 2.1 K/μl, hemoglobin 7.0 gm/dl, platelet count 38 K/μl.
The differential count showed blasts 20%, neutrophils 23%, lymphocytes 55%, eosinophils 1%, and
monocytes 1%.
Diagnosis: “Blastic plasmacytoid dendritic cell neoplasm”
Differential Diagnosis:
• Acute lymphoblastic leukemia
• Acute monoblastic/monocytic leukemia
• Lymphoma involving the peripheral blood and bone marrow
• Acute undifferentiated leukemia
• OR any kind of hematopoietic malignancy!!!
Microscopic: Peripheral smears showed blastic cells with agranular blue cytoplasm and convoluted nucleus
with inconspicuous nucleoli and fine reticular chromatin. Bone marrow core biopsy showed hypercellular
marrow for age and areas showing possible tumor cell infiltrate. High power view showed monomorphic
blastic cells.
Flow cytometry and Immunohistochemistry:
Positive: dim to moderate CD45, CD56, TCL1, CD123, Tdt (dim), CD117 (subset), CD7 (subset), CD4
(subset), CD45RA (subset)
Negative: CD1a, surface and cytoplasmic CD3, CD5, CD8, CD13, CD14, CD19, CD20, surface and
cytoplasmic CD22, CD34, CD64, myeloperoxidase, and other myelomonocytic, B-cell, and T-cell lymphoid
markers
Discussion:
- Rare (approximately 250 cases reported in the literature) clinically aggressive tumor derived from
precursors of plasmacytoid dendritic cells
- There is no known racial or ethnic predilection, with male to female ratio of 3:1. Commonly seen in the
elderly, but can also occur in childhood
- Median survival 12-14 months
- Most patients show initial response but relapse subsequently
- Young patients treated with induction chemotherapy followed by stem cell transplantation may achieve
a long-term remission
References:
• 1: Jegalian AG, Facchetti F, Jaffe ES. Plasmacytoid dendritic cells: physiologic roles and pathologic
states. Adv Anat Pathol. 2009 Nov;16(6):392-404.
• 2: Jegalian AG, Buxbaum NP, Facchetti F, Raffeld M, Pittaluga S, Wayne AS, Jaffe ES. Blastic
plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications.
Haematologica. 2010 Nov;95(11):1873-9.
• 3. Blastic plasmacytoid dendritic cell neoplasm. F. Facchetti, D. M. Jones, T. Petrella et al. in WHO
classification of tumours of haematopoietic and lymphoid tissue. Swerdlow S.H., Campo E, Harris N.L.,
Jaffe E.S., Stein H., Thiele J., Vardiman J.W (Editors), IARC Press, Lyons, France 2008: 214-217.
• 4. Juehua Gao, MD, PhD, Amy Chadburn, MD, and Yi-Hua Chen, MD. Blastic Plasmacytoid Dendritic
Cell Neoplasm: Report of a Case With Extracutaneous Presentation and Extensive Bone Marrow
Involvement. Pathology Case Reviews. 17(3):114-119, May/June 2012.
Case #6
Presenter: Woodlyne Roquiz, D.O.
Attendings: Maria Picken, M.D., Ph.D and Saeedeh Masoom, M.D.
Clinical History: 65 year old male with medical history of hypertension, Type 2 DM, hyperlipidemia and legal blindness.
The patient reports bilateral testicular pain and left groin discomfort. He was found to have a left extratesticular mass.
Testicular ultrasound showed a hypoechoic extratesticular mass extending cephalad to the inguinal canal in close
proximity to the spermatic cord measuring 8.6 x 4.6 x 2.7 cm with arterial and venous waveforms within.
Diagnosis: Angiomyofibroblastoma-like Tumor (Cellular angiofibroma) of the male genital tract
Differential Diagnosis:
 Agressive angiomyxoma
 Pleomorphic Undifferentiated Sarcoma (Malignant fibrous histiocytoma)
 Angiomyofibroblastoma
 Schwannoma
 Liposarcoma
Key Morphologic Features:
Gross: gelatinous soft tissue fragment with a yellow-tan and nodular cut surface.
Microscopic: Review of the specimen reveals a soft tissue neoplasm that has myxocollagenous matrix, many
thick-walled vessels (with focal hyalinization, intraluminal thrombi and perivascular xanthoma cells) and
numerous spindled cells with mild to moderate atypia. There is no definite evidence of malignant transformation.
A small amount of mature adipose tissue is present without evidence of cytologic atypia. Occasional mitotic
figures are noted.
Immunohistochemistry and Special Stains:
Positive: CD34, desmin, and ER protein
Negative: h-Caldesmon, myogenin, AE1/AE3, and S100
Discussion:
 Angiomyofibroblastomas-like tumors are rare, benign, slow-growing tumors that occur in the spectrum of
extratesticular mesenchymal neoplasm of the scrotum and perineum. Of the cases reported in male patients,
most occur in the scrotal and inguinal regions
 A few examples have been reported to undergo sarcomatous transformation and metasasis so adequate clinical
and surgical follow-up is ideal
 Review of the literature states that tumor cells can exhibit immunoreactivity for vimentin (seven of seven cases),
progesterone receptor protein (five of seven cases), CD34 (four of eight cases), estrogen receptor protein (three
of seven cases), desmin (three of eight cases), muscle-specific actin (three of eight cases), and smooth-muscle
actin (two of eight cases) but not for S-100 protein5
References:
1: Shintaku M, Naitou M, Nakashima Y. Angiomyofibroblastoma-like tumor (lipomatous variant) of the inguinal region of a
male patient. Pathol Int. 2002 Sep;52(9):619-22.
2: Iwasa Y, Fletcher CD. Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases. Am J
Surg Pathol. 2004 Nov;28(11):1426-35.
3: Canales BK, Weiland D, Hoffman N, Slaton J, Tran M, Manivel JC, Monga M.Angiomyofibroblastoma-like tumors
(cellular angiofibroma). Int J Urol. 2006 Feb;13(2):177-9.
4: Lee SH, Yang JW, Do JM, Seo DH, Jung JH, Chung KH, Lee JS, Hyun JS. Angiomyofibroblastoma-like tumor of the
scrotum. Korean J Urol. 2010 May;51(5):365-7.
5: Laskin WB, Fetsch JF, Mostofi FK. Angiomyofibroblastomalike tumor of the male genital tract: analysis of 11 cases
with comparison to female angiomyofibroblastoma and spindle cell lipoma. Am J Surg Pathol. 1998 Jan;22(1):6-16.