Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum that has been of public health concern for centuries. In the United States, it is currently a ...reportable disease and one which is recently generating increasing case numbers especially in at risk populations of immune deficiency and men who have sex with men. The present series examines biopsies from 13 patients collected over a 12-year period from a general hospital network in north suburban Cook County, Illinois. There were 13 patients (11 male: 2 female) with varied presentations, including primary ulcerated anogenital chancres, mucosal lesions, peculiar rashes, and alopecia. The reason(s) for biopsy were not clear from the clinical record, as a clinical consideration of syphilis was recorded in only 3 cases. Histologic examination of the mucocutaneous lesions encompassed a spectrum of findings including ulceration, psoriasiform hyperplasia, intense mixed band-like inflammation at the dermal-epidermal junction with a prominent plasma cell component. The contemporary availability of an effective immunostain is a valuable diagnostic adjunct. The organisms generally parallel the intensity of the inflammatory infiltrate but the distribution may vary and rarely, organisms may be absent despite serologic confirmation. Previous corkscrew morphology of the organism described ultrastructurally is reflected in the immunostained representation. Although the diagnosis of syphilis remains a clinical one in most cases, some patients will have unusual presentations and biopsies will be done. The awareness of the pathologist will facilitate prompt and effective treatment.
A 36-year-old male was found to have a 7.0 cm left upper pole renal mass on renal ultrasound. Following nephrectomy, the mass was grossly ill-demarcated, friable and red-brown, invading renal ...parenchyma, hilar fat and the renal vein. Microscopically, the tumor had a nested and papillary architecture. The cells demonstrated abundant clear and eosinophilic cytoplasm and focal intracytoplasmic melanin pigment. Nucleoli were prominent. By immunohistochemistry, the tumor was positive for TFE3; HMB-45 stained approximately 5% of tumor cells corresponding to the histologic melanin pigment, which was confirmed with Fontana-Masson stain with bleach. Immunostains for PAX8, CD10, MiTF, and CAIX were negative; keratins Cam 5.2 and AE1/AE3 were focally positive. Targeted next-generation sequencing revealed an ARID1B-TFE3 gene fusion. Melanotic Xp11 renal cell carcinoma is a rare, pigment containing translocation variant demonstrating overlapping features with melanoma and is usually associated with an SFPQ-TFE3 gene fusion. The patient is alive and without evidence of disease 7 years after his diagnosis. The combination of high grade histopathology, the presence of melanin, absent PAX8, keratin positivity, and relatively indolent clinical behavior with a unique translocation may warrant recognition as a distinct renal cell carcinoma translocation subtype.
To evaluate the relationship between a positive resection margin in partial nephrectomy (PN) and local recurrence.
From January 2005 through December 2012, there were 473 PNs in 466 patients at the ...University of Chicago. A positive margin was defined as tumor extending to the inked specimen edge, either the parenchymal interface or the peripheral fibroadipose tissue. A local recurrence was defined as an ipsilateral tumor of identical histologic type.
Renal cell carcinoma (RCC) accounted for 406 tumors: 243 clear cell RCCs (CRCCs), 77 papillary RCCs (PRCCs), and 47 chromophobe RCCs (CHRCCs). Sixty-one RCCs had positive margins: 43 CRCCs, six PRCCs, nine CHRCCs, and three miscellaneous cell types. Of the 61 positive margins, four CRCCs (all originally multifocal) had a local recurrence, two of which occurred in the same patient. One translocation RCC also recurred. Six cases with negative resection margins had a recurrence.
A literature review of 3,803 cases, including our study, shows positive margins in 173, of which 13 recurred; however, 39 with negative margins also recurred. A positive margin in PN seldom correlates with a local recurrence. However, protection from recurrence is not ensured by a negative margin.
Renal medullary carcinoma is a rare, well-recognized highly aggressive tumor of varied histopathology, which occurs in young patients with sickle cell trait or disease. Rhabdoid elements, ...occasionally seen in high-grade renal tumors including renal medullary carcinoma, possibly represent a pathologic marker of aggressive behavior. INI1 (hSNF5/SMARCB1/BAF47) is a highly conserved factor in the ATP-dependent chromatin-modifying complex. Loss of this factor in mice results in aggressive rhabdoid tumors or lymphomas. In humans, the loss of INI1 expression has been reported in pediatric renal rhabdoid tumors, central nervous system atypical teratoid/rhabdoid tumors and epithelioid sarcomas, a possible primary soft tissue rhabdoid tumor. This study compares five renal medullary carcinomas with 10 high-grade renal cell carcinomas (five with rhabdoid features), two urothelial carcinomas and two pediatric renal rhabdoid tumors. All five renal medullary carcinomas, irrespective of histopathology, showed complete loss of INI1 expression similar to that seen in pediatric renal rhabdoid tumors. In contrast, all renal cell carcinomas or urothelial carcinomas, including those with histological rhabdoid features, expressed INI1. Clinically, all five of the patients with renal medullary carcinoma and the two patients with rhabdoid tumors presented with extra-renal metastases at the time of diagnosis. This study demonstrates that renal medullary carcinoma and renal rhabdoid tumor share a common molecular/genetic alteration, which is closely linked to their aggressive biological behavior. However, the absence of INI1 expression is not necessarily predictive of rhabdoid histopathology but remains associated with aggressive behavior in renal medullary carcinoma.
Objective:
The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis LTB), Mycobacterium ...fortuitum (laryngeal Mycobacterium fortuitum LMF), and Blastomyces dermatiditis (laryngeal blastomycosis LB).
Method:
Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms.
Results:
Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF.
Conclusion:
Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.
Understanding the developmental relationship between indolent and aggressive tumors is central to understanding disease progression and making treatment decisions. For example, most men diagnosed ...with prostate cancer have clinically indolent disease and die from other causes. Overtreatment of prostate cancer remains a concern. Here we use laser microdissection followed by exome sequencing of low‐ and high‐grade prostate cancer foci from four subjects, and metastatic disease from two of those subjects, to evaluate the molecular relationship of coincident cancer foci. Seventy of 79 (87%) high‐confidence somatic mutations in low‐grade disease were private to low‐grade foci. In contrast, high‐grade foci and metastases harbored many of the same mutations. In cases in which there was a metastatic focus, 15 of 80 (19%) high‐confidence somatic mutations in high‐grade foci were private. Seven of the 80 (9%) were shared with low‐grade foci and 65 (82%) were shared with metastatic foci. Notably, mutations in cancer‐associated genes and the p53 signaling pathway were found exclusively in high‐grade foci and metastases. The pattern of mutations is consistent with early divergence between low‐ and high‐grade foci and late divergence between high‐grade foci and metastases. These data provide insights into the development of high‐grade and metastatic prostate cancer.
The overwhelming majority of somatic mutations in coincident low and high grade prostate cancer foci are private, suggesting these foci diverge early from a common progenitor. In contrast, synchronous metastatic disease contains few mutations not already present in high grade prostate cancer foci.
A total of 704 cases of thyroid cancer were retrospectively reviewed (2005 to 2011) to assess the contribution of frozen section (FS) to preoperative fine-needle aspiration (FNA). There were 613 ...papillary carcinomas (87.1%), of which 237 were <1.0 cm. FNA was diagnostic or suspicious in 39.9% of micropapillary thyroid carcinomas and 75.8% of papillary carcinomas. FS was diagnostic in 52.3% and 76.6%, respectively. In no instance did the FS diagnosis change the procedure (total or near-total thyroidectomy). Neither FNA nor FS was diagnostically definitive in follicular neoplasms. A diagnosis of follicular carcinoma was made only after thorough histologic analysis. FS should have a less prominent role in the management of thyroid masses, especially in the context of total thyroidectomy for benign disease. FS may be more productively applied to the identification of metastatic lymph nodes or parathyroids in the surgical field.
Frozen section is a prominent point of intersection between surgeons and pathologists. It is regarded as the most definitive--but not the sole--form of intraoperative consultation. Its role in tissue ...triage, diagnosis, and intraoperative management should not be misconstrued as a shortcut to a definitive diagnosis. Although the pathologist remains in control of the tissue disposition, frozen sections are ideally requested and executed as a collaborative effort. Frivolous requests with no direct consequences for the conduct of a given procedure should not be honored. Frozen section plays a material role in resident education and may be the last vestige of general surgical pathology in an era of organ system specialization. Frozen section will retain its relevance only in the context of broad clinical knowledge by the pathologist and judicious utilization by the surgeon, both in the ultimate service of the patient.
Parathyromatosis is displaced parathyroid tissue in the neck and mediastinum related to prior surgery. Parathyromatosis can be difficult to distinguish from atypical adenoma and parathyroid ...carcinoma. The aim of this study is to evaluate clinical and morphologic features that may differentiate parathyromatosis, atypical adenoma, and parathyroid carcinoma. Cases of parathyromatosis, atypical adenoma, and parathyroid carcinoma were identified. Index cases were reviewed by consensus for histologic features, including stromal, cytologic/architectural, and invasive features. Ki67 was performed on index cases and scored using the Adsay method. Clinical information was gathered from the electronic medical record. 4 parathyromatosis, 17 atypical adenoma, and 6 parathyroid carcinoma were included. Parathyroid carcinomas were more likely to display coarse chromatin with nucleoli (
P
= 0.04), infiltrative invasion (
P
< 0.01), and metastasis (
P
< 0.01). Only parathyromatosis showed circumscribed invasion. Infiltrative invasion was more common in cases with progression (
P
= 0.046) and metastasis (
P
< 0.001). Necrosis and perineural invasion were only present in cases with progression and were more frequent in cases with metastasis (
P
= 0.079 and
P
= 0.19, respectively). There were no differences in presence of a fibrous capsule, capsular invasion, intralesional fibrous bands, random endocrine atypia, solid growth, Ki67 index, gland size/weight, serum PTH/calcium levels, and locoregional recurrence rates. There is overlap in the histologic features in parathyromatosis, atypical adenoma, and parathyroid carcinoma. While perineural, vascular, and infiltrative soft tissue invasion should remain diagnostic of malignancy, other atypical features such as solid growth, coarse chromatin with nucleoli, and necrosis should raise concern for recurrence and/or metastasis, and can be present in parathyroid lesions with and without recurrence.
Echinococcus is the smallest of the major tapeworms. Humans are incidental hosts who become infected by exposure to soil contaminated with ova from the feces of the canine definitive hosts. The major ...species are E. granulosus (cystic echinococcosis) and E. multilocularis (alveolar or sylvatic echinococcosis), both common worldwide but unusual and not reportable in the United States. Human disease is characterized by slowly growing visceral cystic masses often containing daughter cysts and hydatid sand. In nonendemic areas, the clinical evaluation includes imaging, serology, and surgery; metastatic tumor is a major consideration. The diagnosis depends on the morphologic recognition of scolices and hooklets, albeit degenerated, within the cyst or attached to the cyst wall. Highly suggestive cyst wall features are an acellular hyaline lining surrounded by focally calcific fibrous tissue and chronic inflammation. We report 7 patients encountered in the Chicago area (5 E. granulosus, 2 E. multilocularis) who presented with cystic masses affecting the liver, lung, soft tissue, and spleen. The initial diagnosis was established or suggested by intraoperative evaluation of cyst fluid or cyst wall histopathology. Organism parts were found in 5 cases; 1 patient had a hyalinized cyst wall with a positive IgG (enzyme-linked immunosorbent assay), and 1 had a positive Western blot and a 30-year history of treatment. Treatment included cyst resection, hepatic lobectomy, intraoperative cyst injection, and benzimidazole therapy. There was 1 death. In a nonendemic area, the awareness of the pathologist to the possibility of this disease will exclude a neoplasm and facilitate prompt antihelminthic treatment.
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