SP Web Unknown Cases:
Case SB5254 GBM
History: 73-year-old female with a mass lesion in the left frontal lobe.
Multiple choices:
A. Brain infarct
B. Glioblastoma multiforme (GBM)
C. Lymphoma
D.Metastatic melanoma
Diagnosis: Glioblastoma multiforme
Histology: The smear shows markedly atypical astrocytic cells in a fibrillary background. The sections display a hypercellular lesion composed of atypical astrocytic cells with marked pleomorphism and cytologic atypia. Some mitoses are noted. Areas of necrosis and vascular proliferation are also seen.
Discussion: This is a typical case of GBM. The patient is an elderly woman with a localized brain lesion. The post-infusion T1 weighted MRI shows an irregular ring enhancement (indicating neovascularization and increased vascular permeability) with surrounding edema in the subcortical white matter of the left frontal lobe. The radiological findings are rather typicalfor GBM. The histology in this case is also characteristic for GBM, including marked hypercellularity, cytologic atypia and pleomorphism, vascular proliferation and areas of necrosis. The tumor cells display pink astrocytic abundant cytoplasm and cytoplasmic processes, which exclude the possibility of lymphoma. Some cells do contain intranuclear inclusions. This maybe mistaken for metastatic melanoma. However, the entire picture of the tumor excludesthe consideration of metastatic melanoma. Some brain infarct can be hypercellular with ischemic necrosis, however, they often do not contain markedly atypical cells. Instead, there would be reactive gliosis, infiltration of reactive lymphocytes and frequent foaming macrophages.
Case s32810 FATWO and SCTAT
History: Pelvic mass in a 26-year-old female with Peutz-Jeghers syndrome.
Multiple choices:
A. Carcinoid tumor
B. Female adnexal tumor of probable wolffian origin (FATWO)
C. Sertoli-Leydig cell tumor
D.Well differentiated endometrioid carcinoma
E. Malignant mesothelioma
Diagnosis: Female adnexal tumor of probable wolffian origin (FATWO)
Histology: The tumor is composed of cords and tubules of epithelial cells in a fibromyxoid background. The tumor cells display moderate to focally severe cytological atypia. Frequent mitosis is noted. Metastatic tumor is seen in the hypogastric lymph nodes. Multifocal sex cord tumor with annular tubules (SCTAT) is noted in the ovary.
Discussion:Intraoperatively, the pelvic mass was found in the left fallopian tube wall and broad ligament. The ovaries were grossly unremarkable. This is a case of FATWO in a patient with Peutz-Jeghers syndrome. It is well-known that patients with Peutz-Jeghers syndrome often have SCTAT in the ovaries, and these tumor/tumorlets are believed to be incidental and benign. FATWO is a rare tumor and has not been well documented in Peutz-Jeghers patients. The tumor arises from or attached to the fallopian tube orthe leaves of broad ligament, and rarely from the ovary. The morphological distinction of FATWO from sex-cord stromal tumor orsurface epithelial tumors can be difficult. Tumor location is a good clue for suspecting a FATWO rather than a Sertoli-Leydig cell tumor. Immunostaining can be useful to differentiate FATWO from surface epithelial tumors or even mesotheliomas. FATWOs are positive for pancytokeratin (AE1/AE3), calretinin, inhibin, CD10, ER and PR. The tumor cells are negative for CK7, CK 20 and EMA. Although typical FATWOs remain localized and show an indolent behavior, some of which may display a more aggressive clinical course. Hypogastric lymph nodes are positive for metastatic FATWO at initial surgery for this patient.
Case 27972 leiomyoma with malignant transformation
History: 40-year-old female with a slow-growing uterine mass for 11 years
Multiple choices:
- Atypical (symplastic) leiomyoma
- Leiomyosarcoma arising in a leiomyoma
- Leiomyoma with symplastic foci
Diagnosis: Leiomyosarcoma arising in a leiomyoma
Histology: The sections show a smooth muscle neoplasm composed predominantly of smooth muscle cells that donot have sufficient atypia or mitotic activity to qualify for a leiomyosarcoma or even an atypical leiomyoma. There is no necrosis. However, a few small foci display marked cytologic atypia and increased mitotic activity (14 mitotic figures per 10 HPF).
Discussion:Uterine leiomyosarcomas are believed to rise de novo directly from the myometrium or endometrial stroma, which undergoes smooth muscle differentiation. Their origin from a preexisting leiomyoma is a controversial issue, and has not been adequately documented. This case may serve as a good example ofmalignant transformation of a leiomyoma into a leiomyosarcoma. In addition to cellular atypia and increased mitosis, these small atypical foci show p53 overexpression. In contrast, the surrounding leiomyoma cells are negative for p53. Furthermore, Ki-67 proliferation index is significantly higher in these foci compared to the surrounding leiomyoma. It is known that P53 overexpression and mutation are often detected in leiomyosarcomas but not in benign and atypical leiomyomas.P53 mutation may be an initiating factor in the malignant transformation. Morphologically, the atypical foci may be mistaken for symplastic changes (atypical leiomyoma). Even though symplastic leiomyomas are characterized by marked cytological atypia and cellular pleomorphism, they have low mitotic counts, low ki-67 proliferation index and lack p53 overexpression.
Case SB4983 medullary Carcinoma of the stomach
History: 81-year-old woman with weight loss and anorexia.
Multiple choices:
A. Malignant lymphoma
B. Metastatic melanoma
C. Medullary carcinoma of the stomach
Diagnosis: Medullary carcinoma of the stomach
Histology: The sections show a poorly differentiated tumor with pushing borders. The tumor cells are poorly differentiated,polygonal with marked cytologic atypia and mitosis, and scattered throughout a prominent lymphoid stroma. The tumor extends into the full thickness of the muscularis propria, but does not extend out into the perigastric soft tissue. All sampled regional lymph nodes are negative for carcinoma.
Discussion: This is an uncommon variant of adenocarcinoma of the stomach. Medullary carcinoma, also called lymphoepithelioma-like carcinoma, has distinct gross and histological appearance and growth pattern. They usually arise in the distal portion of the stomach with grossly bulky tumor. However, the tumor tends to have a pushing border rather than being infiltrative. There is a dense lymphoid infiltrate composed of both B and T lymphocytes. It has been shown that medullary carcinoma cells contain Epstein-Barr virus (EBV) genetic sequences. Despite its ugly cytology, medullary carcinoma of the stomach has a better prognosis than ordinary gastric carcinoma on a stage for stage basis.
Case S44639 partial mole
History: 28 year-old female with missed abortion at 10 gestational weeks
Multiple choices:
A. Early complete hydatidiform mole
B. histologically unremarkable decidua and villi
C. Partial hydatidiform mole
D. Abnormal villous morphology associated with monosomy or trisomy
Diagnosis: Partial hydatidiform mole.
Histology: The sections contain deciduaand villi. No fetal parts are present. There are enlarged hydropic and small fibrotic villi. The enlarged villi show scalloped villous surface with proliferating trophoblast projecting randomly from the villous surface. In addition, cisterns and occasional trophoblastic inclusions are also noted.
Discussion: This is a well documented case of partial hydatidiform mole. Although the clinical presentation is nonspecific, the sections show typical morphology for partial mole. There aretwo distinct populations of chorionic villi, i.e., small fibrotic villi and enlarged hydropic villi. The latterdisplays irregular scalloped villous surfaces, cistern formation, stromal trophoblastic inclusions and remarkable trophoblastic proliferation. Karyotyping analysis revealed that the chromosomal make-up of the chorionic villi is 69 XXX, which confirms the diagnosis of partial hydatidiform mole. Partial mole can be very difficult to distinguish from early complete hydatidiform mole or atypical villous morphology associated withfetal monosomy or trisomy. The trophoblastic proliferation is quite pronounced in this case, give rise an initial impression of early complete mole. However, it lacks features of early complete mole, such as a labyrinthine network of villous stromal canaliculi, hypercellular villous stroma with kayorrhexia, and significant trophoblastic atypia.On the other hand, abnormal villous morphology caused by fetal monosomy or trisomy often show less degree of trophoblastic proliferation and surface scalloping. Instead of two distinct populations of villi, most villi in monosomy or trisomy tend to be more fibrotic. In occasions when diagnosis can not be reached based on morphology, karyotyping, flow cytometry or FISH canbe very useful in cases of partial mole due to its unique karyotype (triploidy). Partial moles are rarely followed by persistent gestational trophoblastic diseases, with a risk of 0.5-4.0%. Nevertheless, short-term clinical follow-up and serum HCG measurements are warranted.
Case S33973 Double cancer
History: 37 year-old female with vaginal and rectal bleeding
Multiple choices:
A. Endometrial endometrioid carcinoma and metastasis to colorectum
B. Rectal adenocarcinoma with metastasis to endometrium
C. Concurrent endometrioid carcinoma of the endometrium and adenocarcinoma of colorectum
Diagnosis:Concurrent endometrioid carcinoma of the endometrium and adenocarcinoma of the colorectum
Histology:Specimen from endometrial curettage revealed compact/cribriform atypical endometrial glands in a desmoplastic stroma, typical for well differentiated endometrioid carcinoma of the endometrium (FIGO grade 1). The sections from transvaginal biopsy show variable size mucinous glandular epithelium with moderate to marked cytological atypia, suggestive of moderately differentiated colorectal adenocarcinoma.
Discussion: This young woman has a significant family history for early-onset colon cancer (her father and a sister). She was diagnosed to haveconcurrent endometrial and colorectal carcinomas. This has been confirmed by immunohistochemical stains. The tumors with endometrioid morphology are positive for CK7, ER, PR and CA125, but negative for CK20. The tumors with colorectal carcinoma morphology areonly positive for CK20, and negative for all other markers. In view of patient’s young age, significant family history and concurrent endometrial and colorectal carcinomas, we speculate that this patient may have hereditary non-polyposis colon cancer (HNPCC) syndrome. HNPCC syndrome is characterized by germlinemutations in DNA mismatch repair genes and by microsatellite instability in tumors. In fact, endometrial carcinoma is the second most common cancer next to colon cancer occurring in female HNPCC patients.It is also interesting to notice that her endometrial carcinoma lacks expression of pTEN(a tumor suppressor, often inactivated in endometrioid carcinomas), while pTEN immunoreactivity wasseen in her colorectal carcinoma.