June 2017

Challenging but not Impossible: Helpful Clues for the Daily Practice of Pancreaticobiliary Surgical and Cytopathology

Michelle Reid, M.D., M.Sc.
Associate Professor,
Emory University


Volkan Adsay, M.D.
Professor of Pathology, Vice Chair,
and Director of Anatomic Pathology
Emory University

Sunday, June 4, 2017
Registration begins at 7:00AM

Westin Hotel South Coast Plaza
686 Anton Blvd
Costa Mesa, CA 92626
(714) 540-2500

Seminar Objectives:
At the conclusion of this seminar, attendees will be able to:

1. Discuss key cyto-histologic features and differential diagnosis of commonly encountered, problematic solid pancreatobiliary tract lesions.
2. Review the cyto-histologic classification and reporting of cystic and intraductal pancreatobilary neoplasms, as well as benefits and limitations of ancillary testing.
3. Emphasize new concepts in classification and grading of pancreatic NET’s with emphasis of morphologic repertoire and differentials.
4. Review the complex periampullary region anatomy and histologic and site-specific classification of associated neoplasms with emphasis on grossing of Whipples.
5. Discuss the approach to gallbladder atypia including subtle clues to diagnosis of dysplasia, recognition of tumoral intraepithelial neoplasia and invasive carcinoma.


December 2016

Evolving Concepts in Soft Tissue Pathology

Andrew L. Folpe, M.D.
Professor and Consultant
Division of Anatomic Pathology
Mayo Clinic, Rochester, MN

Hyatt Regency San Francisco
5 Embarcadero Center
San Francisco, California, 94111
Phone: (415) 788-1234

December 4, 2016
8:30 a.m. – 4:45 p.m.

Seminar Objectives:

1. Recognize the clinical and morphological features of newly or more completely described entities in soft tissue tumor pathology

2. Effectively apply established and new immunohistochemical markers to the workup of soft tissue tumors

3. Appreciate the impact of advances in molecular pathology to the differential diagnosis of soft tissue tumor


December 2015: A 74 year old woman with abdominal pain

History: 74-year-old gravida 1, para 1 female with a history of hysterectomy and bilateral salpingoopherectomy for severe pelvic endometriosis who presented with abdominal pain. A CT scan demonstrated a 6 cm pelvic mass lying between the bladder and rectum. Fecal occult blood test was positive. The patient underwent attempted resection of the pelvic mass, as well as a sigmoid colon resection.

Gross examination of the resection specimens demonstrated a 10 cm mass that is adherent to the sigmoid colon mass. Also received was a 3 cm aggregate of fragments of tumor designated as pelvic tumor. Microscopically, the tumor comprised large expanses of a spindled mesenchymal neoplasm with relatively monotonous nuclear features, moderate atypia, and indistinct cytoplasm (Fig.1). Occasional areas showing true epithelial gland formation were present, with surrounding hypercellular condensations of the atypical mesenchymal elements (Fig.2). There was prominent stromal overgrowth, resulted in polypoid epithelial projections forming “leaf-like’ low-power appearance (Fig.3). Mitotic figures were easily identified (up to 8 per 10 HPF) (Fig.4). Foci of endometriosis in the bowel serosa were also present (Fig.5). The overlying bowel mucosa was ulcerated, but was without dysplasia (Fig.6).


Extrauterine Mullerian Adenosarcoma with Sarcomatous overgrowth
Suneetha Chintalapati, M.D., Donald R. Chase, M.D. and Jeremy K Deisch, M.D.
Department of Pathology and Human Anatomy
Loma Linda University Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California

Discussion: Mullerian Adenosarcoma is an uncommon mixed epithelial-mesenchymal tumor of low-grade malignancy that affects the female genital tract. Mullerian adenosarcoma is regarded as a lesion with intermediate pathologic features and prognosis, lying between benign adenofibroma and carcinosarcoma.
Extrauterine Mullerian adenosarcoma is very rare, and is presumed to arise in foci of endometriosis, given its frequent co-existence (as seen in this case). Extrauterine examples are more aggressive than uterine tumors, due to ease of access to the peritoneal cavity, as it is not retarded by the thick myometrial wall. The recurrence rate following surgery is higher. Extrauterine Mullerian adenosarcomas are the second most common malignancy arising in extraovarian endometriosis, following clear cell carcinoma. Exogenous or endogenous estrogen may have some role in the transformation process, whereas the effectiveness of combined estrogen–progesterone hormone replacement therapy is still to be determined.

There are currently two recognized sets of criteria for the pathologic diagnosis of malignant transformation of endometriosis. Sampson’s criteria for malignant transformation of endometriosis requires that there is a focus of endometriosis in close proximity to malignancy, that the tumor shows a histological appearance compatible with endometrial origin, and that that other primaries are appropriately excluded. The criteria set forth by Clement and Scully requires a mitotic count of two or more per ten high-power fields, the presence of stromal cellular periglandular cuffs, intraglandular protrusion of cellular stroma, and at least a moderate degree of nuclear atypia of the mesenchymal elements.

Pathologically, Mullerian adenosarcomas are biphasic tumors, in which there are glands lined by benign or mildly atypical Mullerian-type epithelium, intimately mixed with a proliferating mesenchymal component that is a low grade sarcoma, with cellularity more pronounced at the periphery of the glands, forming periglandular cuffs. The immunoprofile is similar to endometrial stromal sarcoma: CD10, WT1, ER and PR are usually positive.
The immunoreactivity for adenosarcomas is similar to that of adenofibromas, which are associated with favorable outcome, as well as other benign lesions such as endometrial polyps and endometriosis. The significant histologic and immunophenotypic overlap between adenosarcomas and adenofibromas suggest that some of the tumors currently classified as adenofibromas, on the basis of their low mitotic count and lack of significant nuclear atypic, are, in fact, well-differentiated adenosarcomas.

Adenosarcomas with sarcomatous overgrowth differ histologically and prognostically from typical adenosarcomas. Sarcomatous overgrowth requires the presence of stromal predominance be present in at least 25% of the tumor volume. In tumors with sarcomatous overgrowth, the mortality rate is as high as 75%, with a similar malignant potential to high grade uterine sarcomas. These tumors may show a high proliferative index by Ki-67 immunostaining, and may show strong p53 staining and loss of CD10 and progesterone receptor immunoexpression.

Malignant transformation of gastrointestinal endometriosis is rare, but when it occurs, it predominantly affects postmenopausal patients. Recognition of these lesions is important as primary gastrointestinal neoplasms are managed differently than those arising in endometriosis. An adenosarcoma arising from endometriosis should be considered in the differential diagnosis of a pelvic mass, even one appearing in the colon wall, because ectopic endometrial tissue has the potential to exist throughout the peritoneal cavity.

Suggested Reading:

Atlas of Gynecologic Surgical Pathology – Clement, Young, 2014, third edition, 256-259.

Clement PB, Scully RE. Extrauterine mesodermal (mullerian) adenosarcoma: A clinicopathologic analysis of five cases. Am J Clin Pathol 1978;69:276–83.

Mullerian adenosarcoma arising from rectal endometriosis, Chunseok Yang etal, Ann Coloproctol. Oct 2014, 30(5): 232-236.

Mullerian Adenosarcoma of the uterus with sarcomatous overgrowth, reecha singh et al, Clin Med Insights case rep. 2010; 3:27-30.

Neoplastic and Pre-neoplastic changes in gastrointestinal endometriosis; Rhonda k. yantiss metal; Am J Surg Pathol 24(4): 513-524, 2000.

Rosai and Ackerman’s Surgical Pathology, 2011, Tenth edition, Volume 2, 1507-1508.

June 2016

Gynecology Pathology Update: Selected Topics with Diagnostic Approach

Brigitte M. Ronnett, M.D.
John Hopkins University, School of Medicine

Westin Hotel South Coast Plaza
686 Anton Blvd
Costa Mesa, CA 92626
(714) 540-2500

June 5, 2016
8:30AM – 4:45 PM

Objectives include:

1. Improvement in the use of modern diagnostic techniques, including IHC and molecular genotyping
2. Knowledge of current criteria for diagnosis of mucinous tumors both primary and metastatic
3. Learning the criteria for serous tumors including borderline and peritoneal lesions.
4. Being aware of challenges of diagnosing invasion for HPV-related endocervical lesions
5. Understanding the utility of IHC for distinction of endocervical and endometrial adenocarcinomas


August 2015: A five year old girl with a cardiac conduction problem

History: A 5-year-old girl presented with cardiac conduction problem. Workup revealed a mass in the right atrium.

Microscopically, the mass consisted of enlarged myocytes with abundant, vacuolated or clear cytoplasm (Fig. 1). At higher magnification, the tumor cells had strands of cytoplasmic myofibrils radiating from the central nucleus to the cell periphery forming so-called “spider cells” (Fig. 2). Cross striations were commonly seen (Fig. 3). Neither necrosis nor mitotic figures were present.

Diagnosis: Rhabdomyoma of the atrium

Li Lei, M.D. and Donald R. Chase, M.D.
Department of Pathology and Human Anatomy
Loma Linda University Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California

Discussion: Primary cardiac tumors are rare. In the young pediatric group, the commonest cardiac tumors are rhabdomyomas (45-63%), followed by fibromas (20%) and myxomas (10-15%); while in teenagers and adults, myxomas account for about two-thirds of primary cardiac tumors.

As its name implies, rhabdomyoma is a benign tumor of striated muscle differentiation. It is considered a hamartoma or malformation other than a true neoplasm, largely because the tumor cells have a very low proliferative index … essentially, they do not proliferate.

Cardiac rhabdomyoma almost exclusively affects infants and young children. About 75% of cases occur before the age of one year. It can occasionally be seen as early as 20 weeks gestational age. Arrhythmia is the most common presentation, though many patients are asymptomatic. Lethal arrhythmia or valvular orifice obstruction can cause sudden cardiac death.

Approximately 51-88% of cardiac rhabdomyomas are associated with tuberous sclerosis, and it may be the earliest sign of tuberous sclerosis in a family. On the other hand, about 43-72% of children with tuberous sclerosis have or will develop cardiac rhabdomyomas. A minority of cases are sporadic. Occasionally, association with folliculin mutation and Birt Hogg Dube syndrome has been reported.

Cardiac rhabdomyomas are often multiple, particularly those associated with tuberous sclerosis. Up to 10% of cases are solitary. It typically presents as intramural lesion in the ventricles, but may protrude into the ventricular cavity as a pedunculated or sessile mass. Interventricular septum and atria can also be involved. Macroscopically, it is well-circumscribed but nonencapsulated, with a homogeneous whitish or grayish cut surface.

Histologically, the cells are big and polygonal. Large cytoplasmic vacuoles are separated by strands of cytoplasm extending radially between nucleus and cell membrane, giving a characteristic “spider cell” appearance. The vacuoles are rich in glycogen which is PAS positive and diastase sensitive. Cross-striations are also routinely seen. Mitotic figures and necrosis are absent.
Ultrastructurally, the cells have abundant glycogen and rare, small mitochondria. Cellular junctions resembling intercalated disks are all around the periphery instead of exclusively at the cell poles as seen in normal cardiomyocytes.

Immunohistochemically, the tumor cells express muscle specific actin (MSA), myoglobin, desmin and vimentin. As with other tumors associated with tuberous sclerosis, cardiac rhabdomyoma is often positive for HMB45 but is usually negative for S100.

The differential diagnosis of cardiac rhabdomyoma includes:

• Histiocytoid cardiomyopathy is extremely rare in patients over the age of 2 years. It presents as subendocardial yellowish nodules or plaques. The large polygonal cells have coarsely granular, foamy to pale eosinophilic cytoplasm resembling histiocytes. They show cholinesterase immunoreactivity but do not express histiocytic antigen(s). The granules are bizarre mitochondria under electron microscope.
• Cardiac hibernoma consists of granular to multivacuolated adipocytes, which are typically S100 positive. The cytoplasmic vacuoles are small and stain for neutral fat. “Spider cells” and cross-striations are lacking.
• Cardiac myxoma often occurs on the left side of the atrial septum. It arises from endocardium as a polypoid mass and does not involve underlying myocardium. Cut surface is gelatinous. Perivascular cuffing by tumor cells within myxoid stroma is commonly seen.
• Cardiac rhabdomyosarcoma is anecdotal in children, with only a few cases reported in the literature. Invasive biologic behavior and malignant histologic features help differentiate. Extensive clinical workup excluding metastasis is necessary before rendering the diagnosis.

Cardiac rhabdomyoma has a tendency to regress spontaneously over time, especially throughout the first year. Approximately 54-100% of cases undergo complete or partial regression. Surgery is therefore reserved for seriously symptomatic patients. If the risk of radical resection outweighs the benefit, a partial resection may be satisfactory given the regressing potential of cardiac rhabdomyoma. In inoperable cases, mammalian target of rapamycin (mTOR) inhibitors such as everolimus and sirolimus have been tried and appear promising.

Suggested Reading:

Goldblum J, Folpe A, Weiss S. Enzinger & Weiss’ Soft Tissue Tumors, 6th ed: Philadelphia, Elsevier Inc, 2014; 591-2.
Suvarna SK. Cardiac Pathology: A Guide to Current Practice. Springer 2013; 201-21.
Basso C, Valente M, Thiene G. Cardiac tumor pathology. Springer 2013; 59-62.
Burke A, Virmani R. Pediatric heart tumors. Cardiovasc Pathol. 2008;17:193-8.
Bondavalli D, White SM, Steer A, Pflaumer A, Winship I. Is cardiac rhabdomyoma a feature of Birt Hogg Dubé syndrome? Am J Med Genet A. 2015;167A:802-4.

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