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The identification of mutations in epidermal growth factor receptor (EGFR) and translocations involving anaplastic lymphoma kinase (ALK) in lung adenocarcinoma has drastically changed understanding of the disease and led to the development of targeted therapies. Adenocarcinoma of the urinary bladder is rare and poorly understood at the molecular level. We undertook this study to determine whether EGFR mutations, increases in EGFR copy number, or ALK translocations are present in these tumors. Twenty-eight cases of primary bladder adenocarcinoma were analyzed. For EGFR mutational analysis, PCR-amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro Kits. All cases were analyzed via fluorescence in situ hybridization (FISH) using Vysis ALK Break Apart FISH Probes for detection of ALK chromosomal translocation and Vysis Dual Color Probes to assess for increased gene copy number of EGFR. None of the 28 cases examined showed mutational events in EGFR or ALK rearrangements. EGFR polysomy was seen in 10 out of 28 (36%) cases. No correlation with EGFR polysomy was seen in the tumors with respect to age, histologic subtypes, pathologic stage, or lymph node metastasis. In summary, EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. A subgroup of cases (36%), however, demonstrated increased gene copy number of EGFR by FISH.

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

The diagnosis of branchiogenic carcinoma is one of significant controversies in the field of head and neck oncology. Those who support its existence adhere to rigid criteria to validate its existence. Those that deny it, purport that the entity is simply metastatic disease masquerading as a branchial cleft primary. One aspect of agreement between the two opposing views is that a separate head and neck primary disqualifies the diagnosis of branchiogenic carcinoma. We report a case in which branchiogenic carcinoma was diagnosed in the presence of an additional base of tongue primary squamous cell carcinoma based on morphologic dissimilarity and evidence of origination from the basal layer of the branchial cleft epithelium. In doing so, we attempt to make the case that unequivocal histologic evidence of branchial cleft origin is the defining feature of branchiogenic carcinoma and, as with many other carcinomas, should be the diagnostic criterion of choice in issuing the diagnosis. A brief pertinent literature review is presented.

Patient: 80-year-old Caucasian female Chief Complaint: Fatigue, flank pain, and hematuria History of Present Illness: The patient was admitted to the regional hospital after transfer orders from her primary care physician (PCP) subsequent to results of a CBC and a several week history of fatigue and hematuria. The PCP gave her ciprofloxacin to treat the presumed urinary tract infection (UTI). Upon a 1-month follow-up, the patient’s symptoms had not resolved, and the PCP discontinued the ciprofloxacin and started the patient on cephalexin. The patient again presented to her PCP, prior to this admission, with flank pain, in addition to the previous symptoms. Performance of a CBC revealed a hemoglobin level of 4.6 g/dL, and the patient was subsequently transferred to the hospital for treatment of profound anemia. Past Medical and Surgical History: Hypothyroidism Family History: Multiple myeloma Social History: Tobacco use (quit 15 years ago) Physical Examination Vital Signs: Temperature: 36.2°C; pulse 82 beats per minute; respiratory rate, 20 breaths per minute; blood pressure, 133/65. Principal Laboratory Findings: Table 1 Additional Testing: Reference Lab Pre-transfusion Workup Cell Studies: Direct antiglobulin test (DAT) positive to polyspecific anti-human globulin (AHG), anti-immunoglobulin G (IgG), and anti-complement; elution studies were not performed at the time. Serum/Plasma Studies: Autoantibody Reactivity: positive Adsorption Studies: Alloadsorption performed: no alloantibodies to common antigens detected Recommendations: Group O; Rh (D) compatible; least serologically incompatible; cross-matched red cells. Consideration should be given to the use of a properly monitored blood warmer; keep all fluids warm; keep patient warm. 1. What are the patient’s most striking clinical and laboratory findings? 2. What is the differential diagnosis for a patient with these findings? 3. What is the patient’s most likely diagnosis? 4. What protocol needs to take place to differentiate among the different types of autoimmune hemolytic anemias (AIHA)? 5. What is the recommended treatment and management …

Answer: a dicotyledonous plant seed. A differential identification of the object initially included both a small intestinal fluke and a cross-section of a nematode, among other possibilities. However, close inspection of the object did not reveal internal structures, such as reproductive and

A 13-year-old male presented to the Riley Hospital for Children at Indiana University Health emergency department with a 2-day history of constipation and a 1-day history of rectal bleeding. He had also passed several stools containing blood following administration of a laxative. At the time of evaluation, the patient was afebrile and denied anti-inflammatory drug ingestion, illicit substance abuse, epistaxis, hematemesis, travel outside Indiana, and consumption of raw or undercooked meat. Digital rectal examination revealed an ulcer in the posterior wall and a hemorrhoid in the anterior wall, while the remainder of the physical examination was unremarkable. A complete blood count and coagulation studies indicated mild anemia and an elevated neutrophil count, but other parameter values were within normal limits. A radiograph of the child's abdomen was also performed, which showed only a moderate amount of gas and stool retention. The patient's medical history was significant for developmental delay and Nissen fundoplication for esophageal reflux. Based on these findings, the patient was admitted for further evaluation by the gastrointestinal service. A colonoscopy performed the following morning confirmed the presence of a raised, erythematous, and friable rectal ulcer, while the rest of the colon and terminal ileum appeared normal. Biopsy specimens of the colon, terminal ileum, and rectal ulcer obtained during the colonoscopy did not reveal an obvious cause of the rectal ulcer, and the intestinal mucosa was unremarkable. However, one hematoxylin-and-eosin-stained section of the colon biopsy specimen revealed an ovoid object containing abundant eosinophilic granules measuring 1.0 by 0.75 mm in the greatest dimension (Fig. 1) in the lumen. The pathologist queried as to the presence of an intestinal parasite. FIG 1 Hematoxylin-and-eosin-stained colon biopsy specimen of the ovoid object (left; ×100 total magnification). The higher magnification demonstrates the cellular structure and outer wall (right; ×600 total magnification). (For answer and discussion, see page 3138 in this issue [doi:10.1128/JCM.00700-13].)