GROUP 1: Case 967-- A Teenage Female with an Ovarian Mass CLINICAL HISTORY A teenage female presented with secondary amenorrhea (https://www.healthline.com/health/secondary-amenorrhea#causes). The patient had 1 menstrual cycle 3 years ago and has had no menses since. Laboratory work-up was negative for pregnancy test, mildly increased calcium level (11.7 mg/dL, normal range: 8.5-10.2 mg/dL) and CA 125 (43 Units/ml, normal range: 0-20 Units/ml). Prolactin, TSH, AFP, Inhibin A, Inhibin B and CEA were normal. Imaging revealed a 13 x 11.8 x 8.6 cm, predominately cystic left pelvis mass, with multiple internal septations. Her past medical history was not contributory. Patient underwent left salpingo-oophorectomy (https://www.healthline.com/health/salpingo-oophorectomy), omentectomy (https://moffitt.org/cancers/ovarian-cancer/omentectomy/) and tumor debulking (https://en.wikipedia.org/wiki/Debulking) with intraoperative frozen section consultation. GROSS EXAMINATION The 930.9 g tubo-ovarian complex consisted of a 20.0 x 16.0 x 8.0 cm large mass, with no recognizable normal ovarian parenchyma grossly and an unremarkable fallopian tube. The cut surface was gray, "fish-flesh", soft with foci of hemorrhage and necrosis. MICROSCOPIC EXAMINATION Microscopically, the majority of main tumor was growing in large nests, sheets and cords with focal follicle-like structures and geographic areas of necrosis. It was predominantly composed of small cells with hyperchromatic nuclei, round to oval nucleus with irregular nuclear contour, inconspicuous to occasional conspicuous nucleoli and minimal cytoplasm. This component was variably admixed with a population of larger cells, which as the name implies composed of cells with abundant eosinophilic cytoplasm, with central or eccentric round to oval nuclei, pale chromatin and prominent nuclei. Both, the small and large cell components demonstrated brisk mitotic activity. All staging biopsies and omentectomy were composed of large cell component. An extensive panel of immunohistochemical stains was performed. Overall, the staining pattern was strong and diffuse in small cell component compared to patchy weak staining pattern in the large cell component. FINAL DIAGNOSIS Small cell carcinoma (https://en.wikipedia.org/wiki/Small-cell_carcinoma) of the ovary, hypercalcemic type (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939673/) DISCUSSION Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive and highly malignant tumor affecting the women under 40. It was first described as a distinct entity by Dickersin et al in 1982 (1). Fewer than 500 cases have been described in the literature and it accounts for less than 1% of all ovarian cancer diagnoses. Due to the initial consideration of epithelial origin, the term of SCCOHT has been used to distinguish this entity from its mimicker, the neuroendocrine or pulmonary type (2). In fact epithelial origin of SCCOHT was recently challenged as new imm.

1. GROUP 1: Case 967-- A Teenage Female with an Ovarian Mass
CLINICAL HISTORY
A teenage female presented with secondary amenorrhea
(https://www.healthline.com/health/secondary-
amenorrhea#causes). The patient had 1 menstrual cycle 3 years
ago and has had no menses since. Laboratory work-up was
negative for pregnancy test, mildly increased calcium level
(11.7 mg/dL, normal range: 8.5-10.2 mg/dL) and CA 125 (43
Units/ml, normal range: 0-20 Units/ml). Prolactin, TSH, AFP,
Inhibin A, Inhibin B and CEA were normal. Imaging revealed a
13 x 11.8 x 8.6 cm, predominately cystic left pelvis mass, with
multiple internal septations. Her past medical history was not
contributory. Patient underwent left salpingo-oophorectomy
(https://www.healthline.com/health/salpingo-oophorectomy),
omentectomy (https://moffitt.org/cancers/ovarian-
cancer/omentectomy/) and tumor debulking
(https://en.wikipedia.org/wiki/Debulking) with intraoperative
frozen section consultation.
GROSS EXAMINATION
The 930.9 g tubo-ovarian complex consisted of a 20.0 x 16.0 x
8.0 cm large mass, with no recognizable normal ovarian
parenchyma grossly and an unremarkable fallopian tube. The
cut surface was gray, "fish-flesh", soft with foci of hemorrhage
and necrosis.
MICROSCOPIC EXAMINATION
Microscopically, the majority of main tumor was growing in
large nests, sheets and cords with focal follicle-like structures
and geographic areas of necrosis. It was predominantly
composed of small cells with hyperchromatic nuclei, round to
oval nucleus with irregular nuclear contour, inconspicuous to
occasional conspicuous nucleoli and minimal cytoplasm. This
component was variably admixed with a population of larger

2. cells, which as the name implies composed of cells with
abundant eosinophilic cytoplasm, with central or eccentric
round to oval nuclei, pale chromatin and prominent nuclei.
Both, the small and large cell components demonstrated brisk
mitotic activity. All staging biopsies and omentectomy were
composed of large cell component.
An extensive panel of immunohistochemical stains was
performed. Overall, the staining pattern was strong and diffuse
in small cell component compared to patchy weak staining
pattern in the large cell component.
FINAL DIAGNOSIS
Small cell carcinoma (https://en.wikipedia.org/wiki/Small-
cell_carcinoma) of the ovary, hypercalcemic type
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939673/)
DISCUSSION
Small cell carcinoma of the ovary, hypercalcemic type
(SCCOHT) is an aggressive and highly malignant tumor
affecting the women under 40. It was first described as a
distinct entity by Dickersin et al in 1982 (1). Fewer than 500
cases have been described in the literature and it accounts for
less than 1% of all ovarian cancer diagnoses. Due to the initial
consideration of epithelial origin, the term of SCCOHT has been
used to distinguish this entity from its mimicker, the
neuroendocrine or pulmonary type (2). In fact epithelial origin
of SCCOHT was recently challenged as new immunostains and
molecular studies become available. Sex cord, germ cell or
neuroendocrine origin has been suggested and SCCOHT is
currently listed within the category of miscellaneous ovarian
neoplasms in 2014 World Health Organization (WHO)
classification (3).
Clinically, SCCOHT are generally diagnosed in second or third
decades of life (peak at 18-30 years). Rare familial cases have
also been reported (4). The symptom is non-specific and is

3. those related to an abdominal or pelvic mass. Approximately
two-thirds patients have hypercalcemia and one-third of patients
presents with signs of hypercalcemia
(https://www.mayoclinic.org/diseases-
conditions/hypercalcemia/symptoms-causes/syc-20355523).
SCCOHT is predominately unilateral, although familial cases
can be bilateral. Macroscopically, the tumor is usually large
predominately solid, tan, or cream-colored with foci of cystic
degeneration. Areas of hemorrhage or necrosis are commonly
seen. Microscopically, the tumor is often composed of diffuse
growth of closely packed neoplastic cells with round to oval
hyperchromatic nuclei and minimal cytoplasm resembling in a
"small round blue cell" appearance. Other growth patterns such
as nests, cords, clusters or single cells can be present. Follicle-
like structures containing eosinophilic, or rarely basophilic,
fluid are seen in ~ 80% of cases. In up to 50% of cases, a
component of large cells with abundant eosinophilic cytoplasm,
eccentric pale nuclei with prominent nucleoli can be present
focally, predominately or exclusively, resulting in a rhabdoid
appearance. In those cases with large cell component, SCCOHT
shows striking morphologic similarity to malignant atypical
teratoid/rhabdoid tumor (AT/RT) of the central nervous system
(CNS) and malignant renal rhabdoid tumor (MRT).
Immunohistochemical studies have described a rather non-
specific profile of variably positive staining for EMA, pan-
keratin, WT1, calretinin, P53 and CD10 and negativity for
desmin, S100, ?-inhibin and TTF-1. Variable
immunohistochemical staining for neuroendocrine markers has
been reported. In 2014, 3 separate groups discovered that
SCCOHT is characterized by deleterious mutation of
SMARCA4, which encodes the BRG1 protein (5-7). Loss of
expression of SMARCA4 (BRG1) on immunohistochemistry is
considered highly sensitive and specific for the diagnosis of
SCCOHT (8,9). Interestingly, genetic alteration of SMARCA4
are also frequent present in malignant rhabdoid tumors. Given
the morphologic and genetic similarity, some authors propose to

4. rename SCCOHT as 'malignant rhabdoid tumor of the ovary'
(10).
The differential diagnosis of SCCOHT includes numerous other
tumors that occurs in young women including juvenile and adult
granulosa cell tumor, poorly-differentiated or unclassified
Steroli-Leydig cell tumor, desmoplastic small round cell tumor,
Ewing family of tumors, lymphoma, ovarian small cell
carcinoma of pulmonary type, metastatic melanoma, etc.
SCCOHT is usually distinguished from these mimickers by its
unique clinical presentation, histological appearance,
immunophenotype and cytogenetic characteristics, especially
the loss of nuclear expression of BRG1.
SCCOHT has a very poor prognosis, with a 33% survival rate
when diagnosed at an early stage and a much more dismal
prognosis with advanced stage at diagnosis. The traditional
management includes surgical resection, followed by multiple
adjuvant chemotherapy. The favorable prognostic parameters
include increased age at diagnosis, normal serum calcium at
presentation, no large cell component and small tumor size (<10
cm) (10).
What is the theme here? Ovarian cancer.
REFERENCES
1. Dickersin GR, Kline IW, Scully RE. Small cell carcinoma of
the ovary with hypercalcemia: a report of eleven cases. Cancer.
1982;49(1):188-97.
2. Young RH, Oliva E, Scully RE. Small cell carcinoma of the
ovary, hypercalcemic type. A clinicopathological analysis of
150 cases. Am J Surg Pathol. 1994;18(11):1102-16.
3. Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO
Classification of Tumours of Female Reproductive Organs.
Fourth Edition. 2014
4. Witkowski L, Donini N, Byler-Dann R, et al. The hereditary
nature of small cell carcinoma of the ovary, hypercalcemic type:
two new familial cases. Fam Cancer. 2017;16(3):395-399.

5. 5. Jelinic P, Mueller JJ, Olvera N, et al. Recurrent SMARCA4
mutations in small cell carcinoma of the ovary. Nat Genet.
2014;46(5):424-6.
6. Witkowski L, Carrot-Zhang J, Albrecht S, et al. Germline and
somatic SMARCA4 mutations characterize small cell carcinoma
of the ovary, hypercalcemic type. Nat Genet. 2014;46(5):438-
43.
7. Ramos P, Karnezis AN, Craig DW, et al. Small cell
carcinoma of the ovary, hypercalcemic type, displays frequent
inactivating germline and somatic mutations in SMARCA4. Nat
Genet. 2014;46(5):427-9.
8. Conlon N, Silva A, Guerra E, et al. Loss of SMARCA4
Expression Is Both Sensitive and Specific for the Diagnosis of
Small Cell Carcinoma of Ovary, Hypercalcemic Type. Am J
Surg Pathol. 2016;40(3):395-403.
9. Karanian-Philippe M, Velasco V, Longy M, et al. SMARCA4
(BRG1) loss of expression is a useful marker for the diagnosis
of ovarian small cell carcinoma of the hypercalcemic type
(ovarian rhabdoid tumor): a comprehensive analysis of 116 rare
gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. Am
J Surg Pathol. 2015;39(9):1197-205.
10. Witkowski L, Goudie C, Foulkes WD, et al. Small-Cell
Carcinoma of the Ovary of Hypercalcemic Type (Malignant
Rhabdoid Tumor of the Ovary): A Review with Recent
Developments on Pathogenesis. Surg Pathol Clin.
2016;9(2):215-26. .
1
MD PROGRAMME

6. Year: Year 2 (Academic Year 2019-2020)
Semester: Semester 4 (Spring 2020)
Course: MED 207 Histology II
Assessment: Case report preparation
Submission:
Assignments:
1. Group 1 assignment:
https://path.upmc.edu/cases/case967/dx.html
2. Group 2 assignment:
https://path.upmc.edu/cases/case759/dx.html
3. Group 3 assignment:
https://path.upmc.edu/cases/case291/dx.html
4. Group 4 assignment:
https://path.upmc.edu/cases/case421.html
5. Group 5 assignment: https://path.upmc.edu/cases/case44.html
https://path.upmc.edu/cases/case967/dx.html
https://path.upmc.edu/cases/case759/dx.html

7. https://path.upmc.edu/cases/case291/dx.html
https://path.upmc.edu/cases/case421.html
https://path.upmc.edu/cases/case44.html
2
Guidelines for writing the case report
You are required to write a case report based on the case
allocated to you. The case describes the
histopathological findings of diagnostic laboratory for the
referred case. You must pretend that you
are the histopathology lab head and you are writing the
scientific report for publication. In writing
the report, follow the following general guidelines:
1. Length of report required 1,800 to 2,000 words, excluding
title, references list, but including any
text boxes, tables and figures.
2. Report needs to be accessible by a general professional
audience.
3. The writing should demonstrate coherence and structure.
Each section should be concise and self-
contained, leading into the next section.
4. Use straightforward language that facilitates understanding.
Avoid complex jargon.
5. The main body of report text should be in a font accessible to
examiners (guidance currently

8. recommends Arial font size 12.)
Required Sections
Name of the Student:
1. Title
The title should be deduced from the case report assigned and
should best describe the case.
2. Introduction
In this section, you should introduce the disease that the patient
suffers from. Refer to the clinical
and histological manifestations. Mention any related diseases or
group of diseases that are similar to
the one under investigation and talk about the prevalence, if
applicable. Use literature sources from
the internet to familiarise yourself with the disease and use
scientific papers to acquire a better
knowledge of the scientific basis of the disease. This section
should not be more than 400-500 words
in length.
3. Materials and Methods
Present the materials and methods used to produce the
histological pictures that appear in

9. the report. Although you did not do the work and no details of
the methods used are given, just by
looking at the pictures (which have short legends) you can
deduce what technique (s) were used to
produce the images. Put yourself in the shoes of the
histopathologist and describe, briefly, the
methodology used to generate the slides. There are cases were
immunohistochemistry was used but
the report does NOT actually say this. You should work out if
an antibody was used and try to find
3
out (if possible from the picture legends) against which antigen
an antibody was used to come to a
diagnosis. This section should not exceed 300 words
4. Results
Present the findings descriptively by referring to the pictures
shown in the report. Each
picture or (group of pictures) must be organised in Figures.
Figures may contain more than one
image of the case. This is preferred in cases that several images
may refer to the same pathological

10. finding. Each figure must contain a short title and a figure
legend. The legend must describe what
the picture shows and use annotation (arrows etc) if necessary
to point to important histological
findings if necessary. The case report you have been assigned
describes the findings, but there is no
direct reference to each picture in the report. You should work
out, by looking at the pictures and by
reading the text of the report, where the abnormality actually
lies and describe it in the figure
legend. Each figure legend must not exceed 40-50 words. You
are not expected to produce more
than 2-3 figures.
5. Discussion
Discuss the findings of this case and the final diagnosis. You
should also relate the findings for
this patient to what is known about the disease. You should talk
about disease management and refer
to any prospects for developing new therapies for this disease.
This section should be around 700-
1000 words.
6. References: You should cite references in the Harvard style.
The number of references should be

11. between 10-15 and be presented in the Harvard style
(https://infolib.blog.jbs.cam.ac.uk/wp-
content/uploads/2013/10/HarvardReferencingStyle-2013.pdf).
https://infolib.blog.jbs.cam.ac.uk/wp-
content/uploads/2013/10/HarvardReferencingStyle-2013.pdf
https://infolib.blog.jbs.cam.ac.uk/wp-
content/uploads/2013/10/HarvardReferencingStyle-2013.pdf
4
Guidance when marking (for the examiner)
Assessment of the written report is based on content and
delivery:
Content: Exploration of topic, breadth/depth of reading, level of
critical thinking.
Delivery: Appearance and structure, organisation and
coherence, clarity of expression.
The following should be used as guidance, along with the
grades for the individual
criteria, when assigning an overall grade for the written report.
The individual criteria
do not carry equal weight, and their relevance will no doubt
vary between students.

12. CONTENT
ORGANISATION
- Full title describing the focus of the report
- Traditional organisation for case report:
- Introduction, Methods, Results, Discussion.
- Kept to a reasonable word count.
15%
CRITICAL REVIEW
- Understood well the importance of the case
- The introduction delivered the context of the case.
- The importance of the case was understood well and delivered
adequately in the discussion.
50%
Understanding of techniques used
- Clear description of the techniques used.
- Logical presentation of the case in the materials and methods
section.
- Clear presentation of the case in the results section.
15%

13. STYLE
- Clear use of English
- Aim for standard for publication
- All abbreviations qualified on first use in the text
- Harvard referencing style, correctly applied in text and
reference list.
- Figures appropriately labelled and presented.
20%