Patterns of Immunoreactivity with TTF-1 Antibodies 8G7G3/1 and SPT24 Suggest Distinct Immunoprofiles Between Most Pulmonary and Nonpulmonary Small Cell Carcinomas.

Introduction. Small cell carcinoma can arise from various sites. Herein, we analyze the ability of 2 thyroid transcription factor-1 (TTF-1) antibodies (SPT24 and 8G7G3/1) to separate pulmonary from nonpulmonary small cell carcinoma. Materials and Methods. We analyzed 26 pulmonary and 83 nonpulmonary small cell carcinomas, and 14 Merkel cell carcinomas. Each tumor was stained with SPT24 and 8G7G3/1. Extent of nuclear staining was scored as diffuse (>50%), focal (11%-50%), rare (1%-10%), or negative (<1%). Results. All pulmonary small cell carcinomas were positive for SPT24 and 8G7G3/1. Four Merkel cell carcinomas (29%) were positive for SPT24 (ranging from rare-to-diffuse), while 2 (14%) showed rare expression with 8G7G3/1. For nonpulmonary small cell carcinomas, 69 (83%) were positive for SPT24 and 40 (48%) were positive for 8G7G3/1. For SPT24 positive tumors, the extent of 8G7G3/1 expression was equal in 17 (25%) and less in 52 tumors (75%), including 29 (42%) that were negative for 8G7G3/1. No nonpulmonary small cell carcinoma had more staining with 8G7G3/1 compared to SPT24. The differences in staining between 8G7G3/1 and SPT24 in the nonpulmonary cohort were statistically significant (P < 0.0001) with no significant difference between primary and metastatic lesions for 8G7G3/1 (P = 0.66) or SPT24 (P = 0.77). Conclusion. Most pulmonary small cell carcinomas are diffusely positive for both SPT24 and 8G7G3/1, whereas most nonpulmonary small cell carcinomas exhibit focal-to-no staining with 8G7G3/1 and significantly less staining with 8G7G3/1 compared to SPT24. However, these trends are not absolute and should be interpreted in conjunction with clinical and radiological findings.

Adenocarcinomas of the Gynecologic Tract Involving the Urinary Bladder: A Series of 16 Cases Potentially Mimicking Urothelial Malignancy.

CONTEXT.­: There is limited literature describing gynecologic adenocarcinomas involving the urinary bladder, and potential diagnostic pitfalls. OBJECTIVE.­: To describe key features distinguishing metastatic (or extension of) gynecologic adenocarcinomas from urothelial carcinomas with glandular differentiation. DESIGN.­: Retrospective review of surgical pathology cases of gynecologic adenocarcinomas involving the bladder, from 2 different institutions, retrieved from surgical pathology archives, was performed. Morphologic features were recorded, along with immunohistochemistry results when available. Electronic medical records were reviewed for clinical and radiographic information. RESULTS.­: Sixteen cases of gynecologic adenocarcinomas (9 endometrial endometrioid adenocarcinomas, 4 endometrial serous carcinomas, 2 high-grade tubo-ovarian serous carcinomas, and 1 cervical adenosquamous carcinoma) involving the bladder were identified. All included cases had mucosal involvement potentially mimicking primary bladder neoplasms, including 4 cases originally diagnosed as urinary carcinomas. Tumors expressed keratin 7 (12 of 13; 92%), PAX8 (11 of 12; 92%), estrogen receptor (11 of 15; 73%), p16 (8 of 11; 73%), progesterone receptor (8 of 14; 57%), GATA3 (5 of 12; 42%), and p63 (3 of 11; 27%); all tumors were negative for keratin 20 (0 of 12). Features supportive of Müllerian origin included prior history of gynecologic malignancy, lack of morphologic heterogeneity in nonendometrioid tumors, and immunophenotypic coexpression of PAX8 and estrogen receptor with absent GATA3. Potential pitfalls seen in a subset of cases included misleading radiologic and cystoscopic findings, replacement of the overlying urothelial mucosa by tumor mimicking precursor lesions, focal GATA3 and/or p63 positivity, and areas of squamous differentiation in tumors of endometrioid histology. CONCLUSIONS.­: A combination of clinical history, certain morphologic features, and proper selection of immunohistochemical stains is key for the correct diagnosis of secondary gynecologic adenocarcinomas involving the urinary bladder.

Nested Subtype of Urothelial Carcinoma in the Upper Urinary Tract: A Series of 15 Cases.

Nested subtype of urothelial carcinoma (NVUC) of the upper urinary tract is rare. While this subtype has an aggressive behavior in the urinary bladder, little is known about this subtype in the renal pelvis and ureter. In addition, due to NVUC's bland morphology and resemblance to von Brunn nests proliferation, which can be florid in the renal pelvis and ureter, establishing a diagnosis of NVUC in these sites can be difficult, especially on small biopsies. Nineteen cases of NVUC of the renal pelvis and the ureter were identified. One was in-house and 18 cases were sent to the genitourinary pathology consult service. Four cases were excluded due to difficulty in obtaining the slides from other institutions. In all, 8/15 (53.33%) cases showed large nested morphology, 4/15 (26.66%) cases showed mixed large and small nested morphology, and only 3/15 (20%) cases showed predominantly small nested morphology. In all cases, the invasive component was pure nested subtype, and tumors were all unifocal. In 8/15 cases, there was the presence of an overlying low-grade papillary urothelial carcinoma. An associated desmoplastic stromal reaction was none/minimal in 12/15 (80%) cases, with a prominent reaction in the remaining 3/15 (20%) cases. Pathologic stages for the resections were pT1 (n=1), pT2 (n=3), pT3 (n=8), and pT4 (n=1). There was only 1 case with a lymph node metastasis at the time of resection who had pT4 disease. Follow-up was available in 10/15 cases, 7/10 cases showed no recurrences or metastases, and the remaining 3/10 cases later developed urothelial carcinoma of the bladder. In 5/15 cases, follow-up could not be obtained. Similar to NVUC in the urinary bladder, NVUC in the upper tract typically lacks an associated desmoplastic reaction and has by definition bland cytology. In contrast to NVUC of the urinary bladder, NVUC in the upper urothelial tract is: (1) more frequently associated with an overlying papillary urothelial carcinoma; (2) more commonly has a large nested pattern; and (3) appears to behave less aggressively.

Low to Intermediate (Borderline) Grade Breast Spindle Cell Lesions on Needle Biopsy: Diagnostic Approach and Clinical Management.

Spindle cell proliferations of the breast are a heterogeneous group of lesions ranging from benign or reactive lesions to aggressive malignant neoplasms. Diagnosis on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma) whereas individual entities can exhibit a large variety of appearances (myofibroblastoma). In this review, lesions are grouped into lineage, when possible, including those showing fibroblastic/myofibroblastic differentiation, ranging from entities that require no additional management, such as scar and nodular fasciitis, to those with unpredictable clinical outcomes such as fibromatosis and solitary fibrous tumor or locally aggressive behavior such as dermatofibrosarcoma protuberans. The review of low-grade vascular lesions includes atypical vascular lesion and low-grade angiosarcoma. Also discussed are various adipocytic lesions ranging from lipoma to liposarcoma, and rare smooth muscle and neural entities more commonly encountered in locations outside the breast, such as leiomyoma, neurofibroma, schwannoma, or granular cell tumor. Optimal histological evaluation of these entities merges clinical and radiologic data with morphology and ancillary testing. We present our approach to immunohistochemical and other ancillary testing and highlight issues in pathology correlation with imaging. Recent updates in the management of breast spindle cell lesions are addressed. In a well-sampled lesion with radiographic concordance, the core biopsy diagnosis reliably guides management and we advocate the inclusion of management recommendations in the pathology report. Precise characterization using up to date guidelines is important to identify a subset of patients who may safely avoid unnecessary surgical procedures. A multidisciplinary approach with close collaboration with our clinical colleagues is emphasized.

Verrucous Squamous Hyperplasia of the Urinary Bladder: A Series of 23 Cases.

CONTEXT.­: There is scant literature describing verrucous squamous hyperplasia of the urinary bladder. OBJECTIVE.­: To investigate the possible association between verrucous squamous hyperplasia and carcinoma. DESIGN.­: The case files of the senior author were searched for cases of verrucous squamous hyperplasia diagnosed between August 2010 and February 2021. Cases with available material were tested for in situ hybridization with human papillomavirus, and cases with available material unassociated with carcinoma underwent immunohistochemistry for p53. RESULTS.­: We gathered a series of 23 cases, the largest to date. Eleven cases were associated with carcinoma at diagnosis. Of the 7 cases unassociated with carcinoma in which follow-up was available, 1 patient (14.3%) was given a clinical diagnosis of carcinoma with recommended cystectomy, 2 (28.6%) had benign diagnoses, and 4 (57.1%) were dead not from disease. Of the 13 cases with available material, 13 (100%) were negative for human papillomavirus by high-risk in situ hybridization. CONCLUSIONS.­: Based on the small number of cases with limited follow-up, it is unclear whether verrucous squamous hyperplasia represents a precursor lesion or simply a high-risk association. Until more evidence is accumulated, patients with verrucous squamous hyperplasia of the urinary bladder should receive close clinical follow-up.

Intraductal Adenocarcinoma of the Prostate With Cribriform or Papillary Ductal Morphology: Rare Biopsy Cases Lacking Associated Invasive High-grade Carcinoma.

Prostatic duct adenocarcinoma, characterized by pseudostratified columnar epithelium, has historically been considered invasive carcinoma, although it may commonly have an intraductal component. Usual (acinar) intraductal carcinoma of the prostate (IDC-P) is a noninvasive high-risk lesion typically associated with high-grade, high-stage prostate cancer. Whereas there have been rare biopsy studies of pure acinar IDC-P or IDC-P associated with only low-grade carcinoma, there have been no analogous series of IDC-P with cribriform or papillary ductal morphology on biopsy unassociated with invasive high-grade carcinoma. We identified 14 patients with biopsies showing IDC-P with ductal morphology, defined as prostatic duct adenocarcinoma confined to glands/ducts with immunohistochemically proven retention of basal cells. Our series includes 12 patients with pure IDC-P and 2 patients with concurrent low-volume Grade Group 1 invasive cancer in unassociated cores. Three patients underwent radical prostatectomy: 2/3 had high-grade cancer in their resection specimen (Grade Group 3, Grade Group 5), including 1 with advanced stage and nodal metastases; 1/3 had Grade Group 1 organ-confined carcinoma and spatially distinct IDC-P with ductal morphology. Five men had only follow-up biopsies: 2/5 had cancer (Grade Group 2, Grade Group 4); 1/5 had IDC-P (on 2 repeat biopsies); and 2/5 had benign transurethral resection of the prostate. In all 5 cases with invasive cancer, the invasive portion was comprised purely of acinar morphology; no invasive ductal component was identified. Five patients did not have follow-up biopsies and were treated with radiation therapy±androgen deprivation. One patient had no follow-up information. In an analogous situation to acinar IDC-P, we propose that rarely there is a precursor form of ductal adenocarcinoma that can exist without concurrent invasive high-grade carcinoma and propose the term "IDC-P with ductal morphology," consistent with the terminology for acinar prostate adenocarcinoma. Until more evidence is accumulated, we recommend reporting and treating patients with IDC-P with ductal morphology in a manner analogous to those with acinar IDC-P. As with pure IDC-P with acinar morphology, we would also recommend not grading pure IDC-P with ductal morphology. Finally, we propose a new addition to the diagnostic criteria of IDC-P to include intraductal lesions with ductal morphology consisting of papillary fronds or cribriform lesions lined by cytologically atypical pseudostratified epithelium.

Nodular Vascular Transformation of the Lymph Node Sinuses Mimicking Sarcomatoid Change in Renal Cell Carcinoma: A Potential Diagnostic Pitfall.

Vascular transformation of the lymph node sinuses (VTS) is an uncommon phenomenon that is believed to occur secondary to obstruction of efferent lymphatics, frequently occuring in retroperitoneal lymph nodes draining cancer. The nodular subtype of VTS, in particular, can mimic metastatic cancer, such as metastatic renal cell carcinoma with sarcomatoid differentiation, potentially resulting in inaccurate tumor grading and/or staging. We present a case of nodular VTS mimicking metastatic renal cell carcinoma with sarcomatoid differentiation in a patient with high-grade clear cell renal cell carcinoma, and explore the relevant differential diagnosis. Awareness of VTS is essential to avoid misdiagnosis of this benign and curative condition.

Cutaneous Coccidiomycosis Masquerading as an Epidermoid Cyst: Case Report and Review of the Literature.

OBJECTIVES: To present a challenging case of inoculatory fungal mycosis mimicking an epidermoid cyst, which may have been easily overlooked by the pathologist. METHODS: We present a case report of a 29-year-old male with a nodule on the right lower back, which was surgically excised and submitted to pathology as a ruptured epidermoid cyst. RESULTS: Histopathologic sections revealed detached soft tissue fragments containing polymorphic granulomas with abscess and suspicious-appearing spherical structures ranging in size from 50 to 200 µm. Some spherules were located within different types of multinucleated giant cells and most were located in close proximity to abscess. Periodic acid-Schiff fungal stain highlighted these structures and a presumptive diagnosis of coccidiomycosis was rendered. Serologic testing was performed which confirmed exposure to Coccidioides immitis, and extensive work-up for evidence of disseminated disease was negative. Subsequently, additional clinical history was garnered which revealed recent travel history to El Paso, Texas, of many weeks duration for military training, conducted mostly outdoors, subjectively with several encounters of being stuck by vegetation during these exercises. CONCLUSION: This interesting case highlights important diagnostic histologic clues to consider when evaluating "routine" cyst specimens and highlights the importance of thorough clinicopathologic correlation, even in the "routine."