International Journal of Surgical Pathology

Objective. We explore the clinicopathologic features of Ewing sarcoma (ES) presenting in older adulthood. Methods. Cases of molecularly confirmed ES arising in patients aged ≥40 years were evaluated. Results. Fifty patients were identified (33 males/17 females; 41-86 years). The majority of tumors (41) arose at extraskeletal sites, while 9 were bone primaries. Twenty-eight cases showed nested architecture, while the remaining cases showed sheet-like growth. Tumor cytology was categorized as conventional (n = 39), crushed (n = 5), clear cell (n = 4), rhabdoid (n = 3), and epithelioid (n = 2). Fifty percent had necrosis, while rosettes were noted in 1 case. Immunostains performed ranged from 1 to 28 (median = 10). Follow-up (n = 43, 1-147 months) revealed 15 patients with metastasis. Conclusion. Although rare, ES should be considered in the differential diagnosis for round cell malignancies in older adult patients. In this cohort, ES is most often extraskeletal, and may show unusual morphologic features, closely simulating more common neoplasms in this age group.

Ischemic colitis (IC) associates with older age, hypertension, and heart disease, among others. Young-onset IC is rare. We aimed to delineate clinical characteristics of young patients (<40 years) with IC. Cases from 1984 to 2017 were re-reviewed. Of the 60 cases available, 52% (n = 31) had histologic features of IC. Fifty-five percent were female with a mean age of 32 (range = 14-40) years. Fifty-eight percent (n = 18) were resections. The most common presentations were diarrhea and abdominal pain. Three teenagers had IC associated with prior surgery, volvulus, and constipation. In the 21- to 40-year group, 43% (n = 12) lacked clinical associations. A second subset (n = 6, 21%) had histories of immune dysregulation (lupus, dermatomyositis, vasculitis) and poorly controlled HIV/AIDS (n = 5, 18%). Smoking and cocaine were endorsed by 1 and 2 patients, respectively. One patient had premature atherosclerosis while another had HMG Co-A lyase deficiency. Vasculitis was identified in 22% of the resections and in none of the biopsies. Nineteen percent of patients died (n = 6) from complications of IC, all treated surgically, including 1 patient previously misdiagnosed as ulcerative colitis; 2 patients died of unrelated causes. While rare before 20 years of age, IC in teenagers relates to mechanical issues and is rare in children. Associations in young adults include immune dysregulation, cocaine and cigarette use, and premature atherosclerosis. Our retrospective cohort had a surgical mortality rate within the range reported by others, highlighting the importance of accurate diagnosis in young individuals.

Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies. Immunohistochemistry (IHC) for CD3 can aid identification of lymphocytes in this context, but it is not evident that counts on hematoxylin and eosin (H&E) and CD3 are comparable. This study aimed to compare the IEL counts in duodenal biopsies using H&E stains and CD3 IHC, and to examine the interobserver variability. Thirty-five paired H&E and CD3 sections were reviewed by 6 pathologists who counted the number of IELs per 100 enterocytes. The counts were categorized into groups: normal (<25 lymphocytes), mildly raised (25-40 lymphocytes), and markedly raised (>40 lymphocytes). CD3 IHC was associated with significantly higher IEL counts than H&E. Four cases with normal H&E counts had raised counts with CD3. There was moderate agreement between observers for both H&E and CD3. Lack of concordance between CD3 and H&E IEL counts suggests that counts derived from the 2 methods may not be comparable to each other and should not be considered equivalent. There was no significant improvement in interobserver variability with CD3 IHC.

Cystic neutrophilic granulomatous mastitis (CNGM) is a histologically characterized variant of granulomatous lobular mastitis that is associated with lipophilic Corynebacterium species. It remains a largely underrecognized entity in India. Our aim was to study CNGM in the Asian Indian population and explore if 16s rRNA sequencing could be used on formalin-fixed paraffin-embedded (FFPE) tissue to identify the causative organism. We studied 24 cases with histological features of CNGM with hematoxylin and eosin, Gram, Ziehl-Neelsen, and Periodic acid–Schiff stains. Tuberculosis-polymerase chain reaction and 16s rRNA gene sequencing on DNA extracted from FFPE was attempted (N = 23). Gram-positive bacilli were seen in 20/24 cases. Routine culture with prolonged incubation yielded Corynebacterium species in 8 cases; 7 of these cases were evaluated by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species identification. C matruchotti was identified in one case by BD Phoenix. MALDI-TOF MS identified the remaining 7 cases as C kroppenstedtii (N = 4) and C tuberculostearicum (N = 2), with no identification in one. Corynebacteria were identified by 16s rRNA sequencing on DNA extracted from FFPE in 12/23 cases using a primer targeting the V5-V6 region that was found to be more conserved in Corynebacterium species. All cases were negative for the diagnosis of tuberculosis. CNGM can be identified by routine stains. Culture using routine media with prolonged incubation is often adequate to isolate the organism. 16s rRNA sequencing on DNA extracted from FFPE tissue can help make an etiological diagnosis in some cases where only paraffin blocks are available.

Neuromuscular and vascular hamartoma (NMVH) is an unusual lesion presenting as intestinal obstruction by stricture formation. It is characterized by a hamartomatous mass comprising haphazardly arranged mesenchymal tissue native to the intestinal mucosa and submucosa. We aimed to characterize the clinicohistopathological spectrum of NMVH in adult subjects with a search for an etiological clue. We reviewed 84 resected specimens (adult cases) of intestinal obstruction in our institute and diagnosed 4 cases with NMVH. A panel of special stains (Masson trichrome, Verhoeff-van-Gieson, and periodic acid–Schiff) and immunohistochemistry (smooth muscle actin, S100, Bcl₂, CD34, vimentin, desmin, CD117, and CD3) were performed in all cases. All cases of NMVH showed characteristic hamartomatous mounds comprising haphazardly arranged smooth muscle, nerves, ganglia, vessels, and collagen with overlying mucosal ulceration. Adjacent bowel showed submucosal fibrosis, muscularis mucosae thickening, and duplication along with vasculopathy. A typical vasculopathy (“vessel-in-vessel” appearance) was seen in the submucosal and/or subserosal veins. Besides, different other forms of vasculopathic changes like obliterative venopathy and concentric myohypertrophy were also seen. One case had vasculitis and the patient died despite successful surgery. One other case was associated with lymphocytic ganglioneuronitis and granulomatous etiology. We conclude that NMVH can be multifactorial in origin although ischemia resulting from vasculopathy appears to be directly causative. The characteristic vasculopathy in the submucosal location may aid in the diagnosis of NMVH in small biopsy samples.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder is a rare neoplasm showing distinct melanocytic and smooth muscle differentiation. We aimed to review the clinicopathologic features of bladder PEComa using all the available cases in the literature, along with 2 new cases from our database. The patients included 15 females and 15 males with a mean age of 39.2 ± 15.3 years. Painless hematuria was the most common clinical presentation. The tumors were usually well circumscribed with a mean tumor size of 4.4 ± 2.7 cm. Bladder PEComas demonstrated nests, trabeculae, or sheets of epithelioid cells with intermixed spindled cells and numerous thin-walled vessels. Immunohistochemical studies showed that the tumors were positive for HMB45 (27/27), cathepsin (4/4), SMA (20/22), and caldesmon (3/3) and were negative for pan cytokeratin (0/18) and EMA (0/4). Molecular studies revealed that PEComa was associated with the TFE3 (n = 3) and EWSR1 (n = 1) gene rearrangements. Treatment included partial cystectomy (n = 18), transurethral resection (n = 8), and radical cystectomy (n = 4). Twenty patients had no evidence of disease during a mean follow-up time of 19.4 ± 17.2 months. Two patients had recurrence, and 1 patient died of metastatic disease. In conclusion, bladder PEComas demonstrate distinct morphologic and immunohistochemical features. Although most tumors follow a benign course, a small subset may develop metastasis and cause death.

Glomus tumor can rarely arise in the central nervous system as a sella turcica mass. In this article, we report a case of sellar glomus tumor in a female patient who presented at the age of 8 years with visual impairment. The tumor recurred at 4 years and 26 years after initial excision and gamma knife therapy. Histologic examination showed a monotonous population of oval cells accompanied by delicate blood vessels, features mimicking pituitary adenoma. The tumor showed histologic progression at the second recurrence. Synaptophysin staining was positive, but chromogranin and CD56 were negative. The tumor cells were negative for epithelial markers but expressed actin and SMA. Awareness of the rare occurrence of glomus tumor at this region, careful analysis of morphology, and appropriate immunohistochemical workup are essential to solve this diagnostic challenge. The clinicopathologic features of all previously reported cases are reviewed.

The standard of care for stage T3 and stage T4 rectal adenocarcinomas involves neoadjuvant chemoradiotherapy followed by either low anterior resection or abdominopelvic resection. The presence of residual adenocarcinoma or positive surgical margins provides useful prognostic information and can influence ongoing adjuvant therapy. Although uncommon, mimics of treated adenocarcinoma may be present in the surgical specimen. A high index of suspicion is critical in avoiding potential false-positive pitfalls, and the exclusion of mimics of treated adenocarcinoma is paramount to accurate diagnosis and treatment. Seminal vesicle epithelium has long been a challenge in differentiating prostatic adenocarcinoma from benign epithelium. However, the role of incidental seminal vesiculectomy in rectal resections due to fibrous adhesion to the rectal wall secondary to chemoradiation has not been studied. As the seminal vesicle epithelium can show markedly atypical nuclei with radiation-type effect at baseline, the potential risk of misinterpretation as residual adenocarcinoma is high. In this article, we present 2 case reports of rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy followed by transabdominal resection (low anterior resection or abdominopelvic resection) with incidental seminal vesiculectomies mimicking either residual adenocarcinoma or residual adenocarcinoma at a margin of resection.

This study reports 2 odontogenic carcinosarcomas, including the clinicopathologic and immunoprofile characteristics of these rare tumors. The first case occurred in a 22-year-old male presenting a bilobular mass involving the gingiva and bone of the premolar region of the left mandible, with paresthesia of the lower lip. Microscopic examination revealed a tumor similar to ameloblastic fibrosarcoma, with atypical mesenchymal cells; however, the odontogenic epithelium also showed atypia. In the second case, a 16-year-old female had a painless, asymptomatic, large intraosseous mandibular lesion. The patient received radiotherapy to treat a rhabdomyosarcoma of the parotid 13 years before. The tumor was composed of atypical spindle cells, positive for vimentin and smooth muscle actin, intermingled with malignant odontogenic epithelium. Both epithelial and mesenchymal components of the tumors showed high index of p53- and Ki67-positive cells. The first case was diagnosed as odontogenic carcinosarcoma possibly originated from an ameloblastic fibrosarcoma, and the second as de novo odontogenic carcinosarcoma possibly caused by previous radiotherapy.

Adenomyoepithelioma is an extremely rare primary cutaneous neoplasm. Although there is ample evidence on the existence of malignant adenomyoepithelioma in the breast, a malignant counterpart in the skin has not been documented. We report a primary cutaneous adenomyoepithelioma (pcAME) with malignant features arising from a spiradenoma in a 39-year-old female patient. The tumor was solid-cystic in appearance and entirely located in the subcutaneous tissue. Histologically, the tumor displayed foci of adenomatous changes and adenomyoepitheliomatous hyperplasia adjacent to a minute spiradenoma. Gradual increase of architectural complexity, cytologic atypia, mitotic activity, and infiltrative growth were observed in a significant portion of the neoplasm, indicative of transformation to adenomyoepithelioma and subsequently low- to high-grade salivary-type epithelial-myoepithelial carcinoma (EMCA). The intimate dual populations of ductal and myoepithelial cells were highlighted by a panel of immunohistochemical stains in all different components of the tumor. Molecular studies revealed a PIKCA3 mutation, a genetic aberration that has been documented in EMCA, particularly of breast origin. The current case documents for the first time a pcAME with malignant features arising from a spiradenoma and suggests adenomyoepithelioma ex spiradenoma as a possible tumorigenesis pathway of this rare cutaneous tumor.

Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.

A 54-year-old woman presented with abdominal pain. Magnetic resonance imaging revealed an upper vaginal mass with no pelvic side wall involvement, nodal, or distant metastasis. Radical hysterectomy was performed. Histology showed trichoblastic carcinoma with hair follicle structures and malignant sarcomatous and carcinomatous components. Hair follicular differentiation was confirmed by positivity to hair follicle markers (Bcl-2, TLE1, CD56/NCAM, and TDAG51) and presence of CD10-positive trichogenic stroma. The tumor involved the vaginal muscularis only (FIGO [International Federation of Gynecology and Obstetrics] stage I) and was excised with clear margins. The patient remained disease free at 3-month follow-up. This is the first case of cutaneous-type carcinosarcoma reported in the vagina, highlighting the difference in histology, immunophenotype, and behavior compared with gynecologic carcinosarcomas.

Tenosynovial giant cell tumor (TSGCT) of localized type is a common disease occurring mostly in the hands. Diagnosis of this tumor is relatively easy to render with hematoxylin-eosin–stained sections as compared with that of TSGCT of diffuse type. However, very rare cases with chondroid metaplasia that have recently been reported mainly in diffuse type can make pathological differentiation from soft tissue cartilaginous tumors extremely difficult. In this article, the authors present the second reported case of TSGCT of localized type showing extensive chondroid metaplasia. Pathological interpretation was difficult without utilizing immunohistochemistry and fluorescence in situ hybridization. One must be careful not to misdiagnose this lesion as cartilaginous tumors of soft tissue, and we suspect at least some chondroblastoma-like chondroma could be reclassified as TSGCT of localized type with extensive chondroid metaplasia. Morphological, immunohistochemical, and molecular genetic characteristics are presented and discussed.

Aims. The aim of this study was to identify potential driver genetic alterations in a dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. Methods and Results. A 24-year-old female underwent resection of an abdominal mass, which on a previous biopsy demonstrated rhabdomyosarcomatous differentiation concerning for embryonal rhabdomyosarcoma. Histologically the resected tumor displayed a high-grade sarcoma with rhabdomyosarcomatous differentiation in the background of well-differentiated liposarcoma consistent with DDLPS. Fluorescence in situ hybridization confirmed MDM2 amplification, as did array-based copy number profiling. Whole-exome sequencing revealed a somatic FGFR1 hotspot mutation and RNA sequencing an LMNB2-MAP2K6 fusion only within the dedifferentiated component. Conclusions. This study represents an in-depth examination of a rare DDLPS with rhabdomyosarcomatous differentiation in a young individual. Additionally, it is also instructive of a potential pitfall when assessing for MDM2 amplification in small biopsies. Despite exhaustive analysis, mutation and gene copy number analysis did not identify any molecular events that would underlie the rhabdomyoblastic differentiation. Our understanding of what causes some tumors to dedifferentiate as well as undergo divergent differentiation is limited, and larger studies are needed.