International Journal of Surgical Pathology

Objectives. Desmoplastic small round cell tumor (DSRCT) is an aggressive round cell sarcoma that arises in the abdominal cavity/pelvis of young males. We sought to expand its clinicopathologic spectrum. Methods. Cases of DSRCT presenting in patients >30 years of age or tumors arising outside of the abdominal cavity/pelvis were retrieved. Results. Thirty-four cases were identified. Sixteen tumors arose at atypical sites (head/neck, intracranial, thigh, axilla/shoulder, inguinal/paratesticular, intraosseous, and uterine corpus). The remaining 18 patients were older than 30 years, and their tumors involved the abdomen or pelvis. The majority of cases showed areas with classic histology, while 6 cases exhibited solid growth and 5 showed macronodular architecture. Cytologic appearance included round cell, rhabdoid, epithelioid, and small cell. Conclusion. DSRCT may arise at nonabdominal locations in both pediatric and adult populations, as well as intra-abdominally in older adults, and these tumors exhibit high rates of metastasis and morbidity.

Aim. To identify the value of processing multiple sections to detect metastasis in lymph nodes (LNs) dissected during gynecologic cancer surgery, and to evaluate the sizes of metastatic LNs in each region to compare with the largest one. Materials and Methods. This retrospective study included 362 patients who had gynecologic cancer with at least one metastatic LN. Slides of 627 metastatic LN specimens were categorized according to the processing technique into single and more than one section (MOS) groups. In the MOS group, the LNs were cut into 2 or 3 parallel slices because their greatest dimensions exceeded 0.5 cm. Sizes of LN metastatic foci (MF) were measured and defined as follows: MF ⩽2 mm as micrometastasis and MF >2 mm as macrometastasis. The largest LN diameters among the metastatic LNs and the largest LNs in those regions were measured. Groups were compared using the Kruskal-Wallis test. Results. Sixty-five (10.3%) of the metastatic LNs included in this study had micrometastases and 40 (6.3%) of them had MF ⩽1 mm. The rate of micrometastasis was higher in the MOS group than in the single-section group (11.8% vs 8.5%, respectively). Twenty-eight percent (n = 175) of metastatic LNs were not the largest, and 55.5% of those were less than 1 cm in diameter. Conclusion. Methods of LN processing and macroscopic evaluation are not standardized, and processing single sections from LNs may overlook micrometastases. The detection rate of micrometastases can be improved by processing multiple sections from LNs.

Supratentorial ependymomas (ST EPNs) are molecularly characterized, of which the RELA fusion positive tumors are the most common and aggressive subgroup. Moreover, histologically, anaplastic ST EPN (ST-AE) often mimic other central nervous system primary high-grade tumors resulting in a diagnostic dilemma. We aimed to study a cohort of ST-AE; evaluate the expression of two RELA fusion-associated markers—L1CAM and p65 (NF-κB); and correlate their expression with clinical and histological parameters. Cases of ST-AE diagnosed in our department from January 2011 to June 2016 (n = 72) were reviewed. A battery of immunohistochemical markers was employed. A total of 65 confirmed ST-AE were included in the study. Age ranged from 9 months to 60 years. There was a slight predominance in the pediatric population (57%). Male-to-female ratio was 1:1.16. Histomorphological features were varied and mimicked other high-grade tumors in several cases. L1CAM immunopositive tumors constituted 26% of cases and were predominantly seen in young children, in the frontoparietal location, and exhibited clear cell morphology with calcification. A consistent pattern of L1CAM immunopositivity was noted in paired primary and recurrent tumor samples. Our study portrays the varied clinical and histomorphological spectrum of ST-AE. The study emphasizes the association of L1CAM immunopositivity with a wide spectrum of histological parameters, literature on which is scant till date. Since ST EPN-RELA are tumors with aggressive behavior, such a correlation would be clinically relevant, particularly when there is limited access to molecular testing.

Objectives. Transducer-like enhancer of split 1 (TLE1) immunohistochemistry is widely used as a biomarker of synovial sarcoma. Spindle cell or desmoplastic melanoma can morphologically mimic synovial sarcoma. The aim of this study was to investigate the expression of TLE1 in melanomas with a spindle cell morphology. Methods. A search of the surgical pathology files resulted in 57 cases of melanomas diagnosed with a spindle cell or desmoplastic component. After review, 8 cases had no definitive dermal spindle cell component and 7 cases had insufficient tissue remaining and were excluded from the study. A total of 42 melanomas were examined for TLE1 immunohistochemistry using a mouse monoclonal antibody (Cell Marque, clone 1F5). Strength and percentage of nuclear TLE1 positivity was graded on a scale from 0 to 3+. Staining for TLE1 was considered positive for 2 to 3+ and negative for 0 to 1+. Results. Nuclear TLE1 expression was identified in 24 (57%) of the 42 melanoma cases with spindle cell morphology (2+, n = 14; 3+, n = 10). TLE1 was considered negative in 18 cases (43%), of which most contained weak staining (1+, n = 14 [33%]) and only a small subset did not show any staining (0, n = 4 [10%]). Conclusion. TLE1 frequently highlights melanomas with spindle cell morphology and is a potential diagnostic pitfall. Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel.

Background. Tumor-infiltrating lymphocytes (TILs) and mismatch repair gene mutation (MMR) status are emerging biomarkers in immunotherapy. MMR status and TILs have significant clinical implications with regard to treatment with checkpoint inhibitors. We designed a study to determine the frequency and prognostic utility of TILs and MMR in advanced unresectable noncolorectal gastrointestinal (NCGI) malignancies. Methods. This is a retrospective cohort study of patients who were diagnosed with advanced noncolorectal gastrointestinal tumors. Biopsy specimens were tested for MMR status by immunohistochemistry along with evaluation of TILs. Kaplan-Meier analysis was performed to determine the impact of TILS and MMR on survival. Results. We analyzed 146 patients; the mean age at diagnosis was 66.4 ± 11.2 years. 65.8% patients were male, and 62.3% patients had stage 4 disease. All cases had proficient MMR status. The percentage of patients with TILs >5 was 50.7%. There was no statistically significant difference in median overall survival (OS) by TILs when stratified by stage of tumor. When stratified by type of tumor, median OS by TILs level was significantly different for hepatocellular cancers (⩽5 TILs, 86 days versus >5 TILs 312 days, P = .031). Conclusions. Our study suggests that MMR-deficient tumors are quite rare in advanced NCGI malignancies. More than 5 TILs per high power field, evaluated simply on a routine hematoxylin and eosin–stained glass slide confer a better prognosis to most noncolorectal gastrointestinal malignancies, especially hepatocellular carcinoma. This has immense clinical utility with regard to eligibility for immunotherapy.

Serous cystadenofibromas are uncommon benign ovarian lesions, consisting of both fibrous and epithelial components, that are usually cystic but may contain solid or papillary architecture that can be confused with a malignancy on imaging. Papillary architecture seen on frozen section may also falsely steer the pathologist in the direction of a diagnosis of a borderline serous tumor. Overcalling the lesion may lead to more aggressive surgery than necessary, so extensive tissue sampling and consideration of this entity is important in possibly avoiding this mistake.

Dedifferentiated liposarcoma shows a wide morphological spectrum. We present a case of dedifferentiated liposarcoma of the spermatic cord in a 66-year-old male that was initially misinterpreted as pseudosarcomatous proliferative funiculitis with mesothelial proliferation.

Composite paragangliomas are rare with less than 20 cases documented in the abdomen, retroperitoneum, and urinary bladder. In this article, we report the first case of composite paraganglioma in the head and neck presenting as a soft tissue mass in the neck adjacent to the carotid artery in a 50-year-old woman. We discuss the clinicopathologic findings and genetic implications, and we review the literature of this rare entity.

Follicular neoplasms of the thyroid gland are most often characterized by follicular-patterned thyrocytes with a neutrally stained cytoplasm, while a minority of cases present with oncocytic differentiation (Hürthle cell tumors). Exceedingly rare variants with a clear cell phenotype have also been reported, both as clear cell follicular thyroid adenomas (ccFTAs) and clear cell follicular carcinomas (ccFTCs). We present a patient with a 30-mm lesion in the thyroid isthmus in which the preoperative cytology proposed a follicular tumor. On postoperative histopathological evaluation, the tumor surprisingly displayed uniform clear-cell differentiation. No nuclear features suggestive of papillary thyroid carcinoma were observed, and differential diagnoses such as medullary thyroid carcinoma, metastatic renal cell, and parathyroid carcinoma were ruled out. The histological investigation revealed intracapsular collections of tumor cells displaying a debatable relation to the surrounding capsule and blood vessels, and the final diagnosis was a follicular tumor of uncertain malignant potential (FT-UMP) as defined by the WHO 2017 classification. As subsets of FT-UMPs with TERT promoter mutations do recur as advanced malignant tumors, a sequencing analysis was undertaken but could not identify TERT promoter mutations at position C228 or C250. To our knowledge, no previous literature has described a clear cell phenotype in an FT-UMP. We therefore advocate that endocrine pathologists should be aware of this entity in addition to ccFTAs and ccFTCs.

Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is usually an inherited malignancy and may be a presenting indicator of familial adenomatous polyposis syndrome although it may occasionally be sporadic. Known CMVPTC mutations include adenomatous polyposis coli (APC) and β-catenin (CTNNB1) genes. Despite its malignant classification, CMVPTC is considered to be a well-differentiated thyroid tumor with a generally good behavior. In contrast, poorly differentiated thyroid carcinoma is an aggressive tumor. We report a case of CMVPTC with poorly differentiated features in a young female without phenotypic features of familial adenomatous polyposis but with known germline alterations of the APC gene. High throughput sequencing showed germline chromosome 5q deletion encompassing the APC gene in all components with additional unique genetic alterations in the somatic components. A single nucleotide substitution (c.1548+1G>A, NM_000038.5) located one base pair downstream of exon 12 of the APC gene was identified in the CMVPTC component, and a pathogenic frameshift deletion in exon 14 of APC (c.3642del, p.Ser1214Argfs*51, NM_000038.5) was identified in the poorly differentiated thyroid carcinoma component. No other cancer-associated genes were identified by our techniques. Our case represents a rare phenomenon of poorly differentiated features in association with CMVPTC. To our knowledge, ours is the only such report of poorly differentiated features arising in association with an inherited CMVPTC.

Adenoid cystic carcinoma is one of the most common salivary gland malignancies with poor long-term prognosis, but the coexistence of sialoliths is extraordinarily rare. In this article, we report a case of 30-year-old woman with a history of submandibular area swelling with intermittent pain increasing during mealtimes that had led her attending physician to diagnose a sialolith in the left submandibular gland on a radiograph 10 years before. However, the surgical specimen proved to be an adenoid cystic carcinoma accompanied with a sialolith. Histopathologically, the submandibular gland was displaced with a fibrous granulation tissue containing a small cribriform carcinoma invading the extracapsular region of the gland. We performed fluorescence in situ hybridization examination with an MYB-NFIB fusion probe of the lesion, with positive results. The patient underwent a supraomohyoid neck dissection as additional procedure because of the possibility of the extracapsular cancer nest remaining around the submandibular gland, but she remains well and disease free 11 years after the first operation.

Endometriosis in men is extremely rare with only a few cases reported in the English literature. Different theories have been proposed as to its origin. In this article, we describe the clinicopathologic features of 2 cases of endometriosis occurring in male patients. The patients’ ages were 50 and 43 years, and sizes were 2 and 5.2 cm, respectively. No significant chemical or hormonal exposure was identified. Both patients presented with a testicular mass. Grossly, both lesions were cystic and contained hemorrhagic fluid. Microscopic examination revealed cysts and occasional glands lined by low columnar to cuboidal epithelium, surrounded by spindle cell stroma with abundant hemosiderin-laden macrophages reminiscent of endometrium. One case was predominantly intratesticular, with a minute focus of endometrial-type glands and spindled stroma within the tunica vaginalis. Focal chronic inflammation and epithelial denudation were present in both cases. The surrounding testicular and epididymal structures adjacent to the cystic mass were unremarkable. In summary, endometriosis is an extremely rare lesion in men. The presence of these lesions in both cases along the route of the Müllerian duct supports the theory that these lesions arise from embryonic remnants. Awareness of this entity is crucial for general pathologists to avoid wrong diagnosis and unnecessary management.

We describe the first case of primary thymic adenocarcinoma with signet ring cell features. The patient was a 39-year-old Filipino male who presented with a huge anterior mediastinal mass extending to the left supraclavicular fossa, which underwent an incisional biopsy. Extensive clinicoradiological work-up showed no evidence of any primary tumor in other organs, and radiological imaging confirmed a primary tumor location in the thymic area. He later developed bilateral pleural and pericardial effusions and eventually died of his tumor. The biopsy contained a neoplastic growth of solid nests made of cells with prominent signet ring features in sclerotic stroma. Immunohistochemically, the tumor cells were reactive for cytokeratin 7, carcinoembryonic antigen, and CD5 and negative for cytokeratin 20, TTF1, napsin A, α-fetoprotein, PAX-8, CD-117, CA19-9, CA-125, CDX2, p63, and CD99. No genetic alterations of ALK, RET, and ROS1 were found, nor was any ALK or ROS1 immunostaining detected, as known to occur in a fraction of primary pulmonary adenocarcinomas. Morphologically, this thymic tumor resembled signet ring cell adenocarcinomas of other locations, including, stomach, pancreas, and lung, but CD5 immunoreactivity strongly supported the clinical and radiological evidence of a primary thymic origin. In the English literature, only 58 cases of primary thymic adenocarcinoma are on record and this is the first report of a signet ring cell variant, which further broadens the morphological spectrum of thymic adenocarcinoma subtypes.

Pulmonary adenofibroma (PAF) is a rare neoplasm that may be related to solitary fibrous tumor (SFT). A subset of PAFs harbor the NAB2-STAT6 fusion that is typical of SFT, but a significant proportion do not. Their distinction is clinically important as SFTs can potentially have an aggressive clinical course, while there has been no report of a PAF behaving in a malignant fashion. We report a case of a 60-year-old male who developed a SFT and PAF in the same lung. The SFT harbored a NAB2-STAT6 fusion, while the PAF did not have any identifiable fusion. This case represents the first instance of a single patient with both of these tumors occurring simultaneously in the same lung.

Sclerosing rhabdomyosarcoma (RMS) is a rare subtype of RMS with unique prominent stromal hyalinization and a pseudovascular architecture. It overlaps morphologically with spindle cell RMS and poses both diagnostic and therapeutic challenges because of its rarity and aggressive clinical course. In this article, we report a case of sclerosing RMS arising from a prior craniotomy site, which demonstrated both sclerosing and spindle cell components. A literature review of RMS with sclerosing morphology identified 122 cases. Our review documents the following: sclerosing RMS occurs in both childhood and adult populations, has a predilection for the head and neck areas, and has a worse prognosis in adults. Sclerosing RMS harbors a high frequency of MYOD1 mutations, conferring a poor clinical outcome. Sclerosing RMS and spindle RMS likely represent a morphologic spectrum of one entity.

A tailgut cyst (retrorectal cystic hamartoma) is an uncommon lesion that develops in the presacral (retrorectal) space. Malignant change in a tailgut cyst is extremely rare and presents as a soft tissue (presacral) or bone (sacral) neoplasm. We report a case of tailgut cyst in which a neuroendocrine tumor developed in a 25-year-old female. Computed tomography and magnetic resonance imaging scans revealed a sacrococcygeal malformation with absent left S4 and S5 and a partly cystic lesion within the right presacral space. Histologically, the lesion contained cystic and solid elements. The cysts were lined by columnar and stratified squamous epithelial cells with underlying patchy smooth muscle. The solid element was a partly necrotic neuroendocrine tumor composed mainly of ribbons of tumor cells, which showed mitotic activity and expressed cytokeratin, chromogranin, and synaptophysin. Histologically, tailgut cysts are lined by epithelium and contain scattered smooth muscle bundles in the cyst wall. Although rare, the possibility of tailgut cyst with neuroendocrine tumor should be included in the differential diagnosis of an enlarging presacral tumor.

Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood with progressive cholestasis evolving to cirrhosis and liver failure, requiring liver transplantation. In this article, we report 2 pediatric cases of severe MDR3 deficiency with paucity of interlobular bile ducts. Both underwent living donor liver transplantation at our center for decompensated liver disease and portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with negative MDR3 immunostaining in the explanted liver. Genetic studies revealed homozygous deletion single base pair deletion in exon 24 of the ABCB4 gene in the second child. The patients are on regular follow-up after liver transplant and are doing well. Our report highlights that cholangiopathy in MDR3 deficiency can lead to ductopenia in pediatric livers.