Richard Cantley

Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

Solid variant of papillary renal cell carcinoma with spindle cell and tubular components.

The solid variant of papillary renal cell carcinoma, when strictly defined as a tumor in which no true papillae can be identified, is extremely rare, with only a few cases reported in the literature. This tumor is characterized histologically by solid sheets of cells without true papillae; nevertheless, immunohistochemical and genetic analysis supports the classification of this tumor as a variant of papillary renal cell carcinoma. We report a case of solid variant of papillary renal cell carcinoma affecting a young man and provide histologic and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature. In addition, we describe the first case, to our knowledge, of a solid variant of papillary renal cell carcinoma to contain a high-grade (sarcomatoid) spindle cell component.

Fine-needle aspiration diagnosis of metastatic urothelial carcinoma: A review

Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine‐needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction. Diagn. Cytopathol. 2012;.

Asteroid hyalosis of the vitreous humor: An uncommon finding

Dear Dr. Bedrossian, Asteroid hyalosis is an uncommon condition affecting the vitreous compartment of the eye. It was first described by Benson in 1894. Historically, it was called asteroid hyalitis as it was thought to occur as part of an inflammatory process; however, the name was later changed to asteroid hyalosis when it became apparent that the process was degenerative. Other historical names for the condition include Benson’s disease, asteroid bodies, and scintillatio nivea. Asteroid hyalosis is more commonly seen in patients in their seventh to eighth decades, and more frequently occurs in males. It is unilateral in most instances, but approximately 10–25% of cases show bilateral involvement. Associations with coronary artery disease, gout, and smoking have been postulated, but no consistent correlations have been shown. In an autopsy case series of 10,801 eyes, the authors found asteroid hyalosis strongly correlated with age, male sex, and posterior vitreous attachment, and found no correlation with diabetes mellitus. A Korean study found stroke history to be the strongest risk factor associated with asteroid hyalosis. Asteroid hyalosis generally does not cause visual symptoms. Clinically, it is diagnosed either by retinal photography or by slit lamp examination, which disclose opaque, iridescent particles that follow eye movement. Recently, others have published findings of abnormal vitreoretinal adhesions detected preoperatively using optical coherence tomography; this may be helpful for clinical diagnosis when asteroid hyalosis is suspected. Histochemically, asteroid hyalosis bodies stain strongly positive for mucopolysaccharides by alcian blue or colloidal iron stains and weakly positive by Oil-Red-O staining. Chemically, the asteroid bodies are composed predominantly of calcium and phosphorus, which are bound to ribbons of complex lipids. Although the pathogenesis of asteroid hyalosis is not well understood, the large quantities of complex lipids and calcium forming the asteroid bodies have been hypothesized to derive from sources exogenous to the vitreous. We report a case of an 82-year-old female who initially presented to her general ophthalmologist with a complaint of decreasing visual acuity in her left eye. Her past ocular history included previous cataract surgery and macular degeneration. Over the preceding several months, her visual acuity had declined from 20/70 to finger counting only in the left eye. The referring ophthalmologist noted a dense vitreous haze consisting of multiple discrete opacities, which had worsened progressively, coinciding with

Metastatic small cell carcinoma of uterine cervix to the thyroid gland diagnosed by ultrasound guided fine needle aspiration (US-FNA) Cytology: A Proactive approach

Dear Dr. Bedrossian, A recent case of metastatic small cell carcinoma of uterine cervix prompted us to write this letter. The patient is a 47year-old female who presented to the clinic with vaginal spotting. Her past medical history was significant for endometriosis and episodes of heavy menstrual bleeding treated with a laparoscopic, supracervical hysterectomy with preservation of the ovaries 5 years prior. Physical exam revealed a mass in the patient’s uterine cervix. Radiologic studies found the mass to be 8 cm in size and attached to the left vaginal wall. A biopsy was performed. Pathologic examination revealed irregular nests of tumor cells in a fibrotic stroma with hyperchromatic nuclei, scant cytoplasm, and brisk mitotic activity. Nucleoli were absent. The tumor cells were positive for chromogranin, synaptophysin, and CD 56 and negative for p63. Based on the histomorphology and immunoprofile, the diagnosis of small cell carcinoma was made. Imaging studies performed during the patient’s tumor work-up, including computed tomography (CT) and positron emission tomography (PET) of the chest, abdomen, and pelvis, revealed no abnormalities in the lungs or mediastinum. Positive findings on the PET scan included the cervical mass, liver nodules, and a discrete focus in the right thyroid lobe with a standard uptake value (SUV) of 5.7. Fine needle aspiration (FNA) and core biopsies of the liver were obtained under CT guidance; however, there was difficulty visualizing the nodules without contrast. Both the FNA and core biopsy specimens revealed benign liver parenchyma with no tumor. In view of the negative results, we contacted the gynecologic oncologist and proposed that the patient be referred to our service for a thyroid FNA of the focal PET positive area. The patient underwent an ultrasound examination of the thyroid in radiology. Ultrasound studies did not reveal a distinct nodule and sampling by FNA was initially discouraged. However, considering the significance of a potentially positive result would have on tumor staging and management, the patient was scheduled for the procedure. After performing our own ultrasound examination, we were able to match the PET positive area with a subtle, isoechoic nodule with ill-defined cell borders. The nodule measured 0.9 3 0.6 3 0.6 cm and was not taller than wider (Fig. 1). Color Doppler examination demonstrated patchy, peripheral intranodal vascularity (grade 2) (Fig. 2). The patient underwent an ultrasound-guided FNA of the lesion performed by a cytopathologist. Aspirated material (Figs. 3 and 4) revealed a cellular specimen composed of “small blue cells” with scant cytoplasm and stippled chromatin arranged singly and in clusters with no background colloid. Crush artifact, nuclear molding, numerous apoptotic bodies, and brisk mitotic activity were appreciated. Immunostains on cellblock material revealed the same immunoprofile as the cervical tumor, for example, chromogranin and synaptophysin (Fig. 5). The diagnosis of metastatic small cell carcinoma to the thyroid was made. This changed the patient tumor stage from IIB to IVB, and patient underwent chemoradiation therapy. The authors have no conflicts of interest associated with this study. The authors have no disclosure of grants or other funding. *Correspondenec to: Luis E. De Las Casas, M.D., F.A.S.C.P.; University of Toledo Medical Center, Department of Pathology, 3000 Arlington Ave., Mail stop 1068, Toledo, OH 43614. E-mail: Luis.DeLasCasas@utoledo.edu Received 29 April 2014; Revised 24 June 2014; Accepted 17 July 2014 DOI: 10.1002/dc.23205 Published online 1 August 2014 in Wiley Online Library (wileyonlinelibrary.com).

Primary Small Cell Carcinoma Arising from a Bladder Diverticulum

A 66-year-old Caucasian male with a 48 pack-year smoking history presented with gross hematuria and worsening pelvic pain. Laboratory results revealed low grade disseminated intravascular coagulation. Imaging was significant for a bladder diverticulum and lytic lesions of the femurs, pelvis and vertebra. Cystoscopy of the diverticulum revealed a mass larger than 5 cm and transurethral resection was performed. Histopathology of the bladder lesion showed sheets and nests of small neuroendocrine cells with dense intervening fibrous stroma (figs. 1 and 2). Necrosis was present and tumor cells stained positive for synaptophysin. No evidence of urothelial carcinoma (UC) was seen and the final diagnosis was small cell carcinoma of the bladder. Bladder diverticula are formed by herniation of the urothelial mucosa through the detrusor muscle. Bladder diverticula can result in urinary stasis which can lead to infection and resultant inflammation. In recent case series diverticula

Cytologic findings of acute leukemia in bronchoalveolar lavage fluid

Bronchoalveolar lavage (BAL) is often performed in patients with acute leukemia developed with respiratory failure or pulmonary infiltrates. Patients usually undergo BAL to rule out infection. Occasionally, however, leukemic infiltrate may be detected. We present a series of 11 cases in which the diagnosis of leukemia was made on the BAL material. We retrospectively reviewed all BAL samples from January 1, 2006 to December 31, 2008. There were a total of 1,130 cases, of which 139 showed malignant cytology, including 10 with leukemia. Sixteen samples were unsatisfactory and 904 were benign, of which 32 had identifiable microorganisms. In additional to the 10 leukemia cases identified, two more were reviewed after the search criteria. The 12 patients (seven men, five women) ranged from 22 to 75 years old. All patients had previously biopsy‐proven leukemia [two acute myelomonocytic leukemia, two acute promyelocytic leukemia, two acute myeloid leukemia (AML) with inv16, two therapy‐related AML, one acute monocytic leukemia, one chronic myeloid leukemia in blast face, one AML with maturation, one myelodysplastic syndrome with excess blasts, and one large granular leukemia]. Four had a prior diagnosis of myelodysplastic syndrome. The time from initial diagnosis of leukemia to BAL ranged from 1 to 233 days, with 8 of 10 occurring within 8 days of diagnosis. Symptoms that prompted BAL included shortness of breath/hypoxia (8), fever (3), chest pain (2), and cough (2). Chest X‐rays in all cases revealed opacities or consolidations mimicking an inflammatory process. Seven patients subsequently died, while three were alive, and, in remission, and two were lost to follow‐up. The presence of a leukemic infiltrate can mimic infection. BAL is a relatively safe and useful diagnostic tool in this setting for differentiating a leukemic infiltrate from an infection/inflammatory infiltrate. The prognosis of patients with lung involvement of acute leukemia is poor. Diagn. Cytopathol. 2013.

The role of peritoneal washings in the diagnosis of endometriosis

Endometriosis, the presence of endometrial tissue outside the uterine corpus, is a common finding in reproductive age women. It is classically diagnosed based on the presence of at least two of the following elements: endometrial glands, endometrial stroma, and hemosiderin‐laden macrophages (HLMs). Although a common finding in surgical pathology specimens at the time of gynecologic surgery, there is little literature on the role of pelvic washings in diagnosing endometriosis. Our study aimed to examine the characteristics of endometriosis in pelvic washings at the time of gynecologic surgery. We report nine cases of endometriosis diagnosed on pelvic washing. Two had a reported history of endometriosis. Four had endometriosis on the concurrent surgical pathology specimen. Liquid‐based cytology was diagnostic of endometriosis in seven patients, including five with glandular cells and HLMs and two with glandular cells, HLMs, and endometrial stromal cells. Cell block was diagnostic of endometriosis in eight patients, including four cases with intact fragments of endometrial glands and stroma. Three cases showed glandular cells and HLMs, while one showed separate fragments of glandular cells and stromal cells. Pelvic washings increased the diagnostic yield for endometriosis at the time of gynecologic surgery, as only four out of nine cases had endometriosis diagnosed on surgical pathology. Cell block in particular aids in the diagnosis, since intact glandular and stromal fragments frequently can be identified.