A 38-year-old woman complained of repeated vague pain near the right lateral hip over the past 8 months. The last attack of pain, provoked by jogging, persisted for approximately 10 days but was not relieved with nonsteroidal anti-inflammatory drugs (NSAIDs). There was no history of previous injury and no fever, chills, or other systemic symptoms. The findings of musculoskeletal examinations were positive for pain in forced maximum flexion-internal rotation position of the right hip. Ely’s test and Patrick’s (Fabere) test were inconclusive. The rest of the examination as well as the general examination was not contributory. All laboratory findings were unremarkable. The radiograph of the pelvis revealed a linear-shaped calcium deposition in the lateral border of the acetabular rim (Figure A).
A preliminary diagnosis of chronic calcific tendonitis of the origin of the rectus femoris was made. After an appropriate discussion with the patient, arthroscopic surgical exploration with the intention to completely remove calcium deposits was undertaken. The same arthroscopic portals were established and an intra-articular diagnostic arthroscopy was performed as in the preceding case. Intra-operatively, milky fluid and a chalky deposit of calcium were debrided. Arthroscopic labral debridement was performed at the end of the surgical procedure.


The patient was a moderately obese 55-year-old woman with complaints of right posterolateral hip pain after walking. Rest and analgesics had given no relief. She did not report any constitutional symptoms. The patient related her first sudden onset of hip pain to a twisting injury of the same hip 3 years earlier. Radiography of the hip joint performed at that time was reported to be normal. The injury was treated with rest for 3 weeks. Throughout the intervening years, the patient had chronic low-grade dull pains in the hip. Two months ago, the pain became acute and was exacerbated by hip motion.
Physical examination disclosed exquisite tenderness over the posterolateral area of the left hip joint, with the limitation of forced maximum flexion abduction of the right hip due to the pain. Patrick’s (Fabere) test was positive. Pain was elicited by moving the hip passively from FAbER (flexion-abduction-external rotation) position to EAddIR (extension-adduction-internal rotation) position. The rest of the physical examination was normal.
An anteroposterior projection radiograph and CT of the left hip revealed a 1.2-cm diameter radio-opacity with irregular borders, located near the superior tip of the acetabulum (Figure A-C). MRI showed evidence of labral pathology and verified the calcification (Figure D).
The diagnosis of chronic calcific rectus femoris tendinitis of the left thigh was made and treatment with arthroscopic surgery was initiated. A similar arthroscopic technique was used for this patient as described previously. During the procedure, the calcium deposit was immediately apparent by simple arthroscopic inspection from the acetabulum side. After opening its capsule, the typical snowstorm pattern appeared (Figure E). The deposit was cleared out. In addition, a type I labral tear was verified during the hip arthroscopy. A non-absorbable suture anchor was used to stabilize the labrum tissue back to the rim of the acetabulum. A radiographic control was performed at the end of the procedure to evaluate the amount of deposit remaining (Figure F). Histological examination of the collected sample showed abundant calcium salt deposits surrounded by several mature trabecular bone and fibrous tissues.


A 35-year-old Sri Lankan female with long standing intermittent headaches presented with recent worsening of headache. Clinical examination performed by the physician revealed normal neurological examination and vision with a visual acuity of 6/6 without any correction. A provisional diagnosis of migraine has been made on a previous occasion and she had been commenced on multiple medications over a period of time including propranolol and flunarazine. This had helped initially, but not in the long term.
The patient was reassured and asked to continue flunarazine. She presented one month later with no relief from her headaches. Examination was unremarkable. Flunarazine was discontinued and she was commenced on topiramate 25 mg at night.
2 weeks later she complained of acute onset blurring of vision. There were no other neurological symptoms. An ophthalmological consultation revealed no significant visual finding except for a bilateral refractive error of – 0.5 diopters. Her visual symptoms persisted to the next day, but did not worsen. Suspecting topiramate induced myopia the drug was discontinued and the patient was referred back to the ophthalmologist who noted a visual acuity of 6/6, normal intraocular pressure and a worsening of refractive error to −3.5 diopters bilaterally. On the 3rd day following discontinuation of topiramate her visual symptoms started to improve and at the end of 10 days her vision was back to normal with no evidence of a refractive error (0 diopters).
A diagnosis of topiramate induced acute myopia was made. An ophthalmologist review 2 weeks later was normal.


A 13-year-old male presented with abdominal pain and fevers for three months. He was found to have leukocytosis (WBC 76.5x103/uL), anemia (Hgb 5.3 g/dL), and thrombocytopenia (platelet count 15.3x103/uL). Flow cytometry on peripheral blood revealed 94% blasts which expressed bright CD10, CD19, partial CD20, CD34, partial CD38, partial TdT, CD79a, and HLA-DR. A bone marrow biopsy showed a hypercellular marrow extensively involved (~95%) by sheets of lymphoblasts. These findings are consistent with a diagnosis of B-lymphoblastic leukemia. The patient was immediately started on induction chemotherapy with AALL0232 high-risk ALL chemotherapy protocol. A follow-up bone marrow biopsy on day 29 showed minimal residual disease (MRD). A normal karyotype was seen in all metaphase cells examined and loss of one copy of the 5′IGH@ was the only abnormality detected in 2.7% of the interphase nuclei studied. The patient subsequently was given treatment per clinical trial AALL0031 and achieved primary remission. Most recently, the patient received a successful allogeneic bone marrow transplant from a female donor.


An 83-year-old man was hospitalized for upper abdominal pain and weight loss of 4 kg over three months. His past history included pulmonary emphysema. A physical examination revealed a hard, palpable mass in the middle upper abdomen of approximately 10 cm in diameter. Laboratory data showed an elevated leukocyte count of 10,800 per mm3, a decreased hemoglobin level of 11.8 g/dL, and a normal tumor marker level of carcinoembryonic antigen and carbohydrate antigen 19-9. Upper gastrointestinal endoscopy showed a large, ulcerated, tumor spanning from the gastric angle to the antrum and extending to the duodenum (). Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma (). Computed tomography (CT) imaging showed a thickened gastric wall, invasion of the pancreas, and lymph nodes swelling at greater curvature of the stomach but did not show any distant metastases (). Fluoroscopy of the upper gastrointestinal tract allowed visualization of the tumor, which was located in the stomach and was 10 cm in diameter (). This imaging also showed adhesion of the stomach and pancreas. Abdominal ultrasonography also suggested invasion of the pancreas. Based on the above findings, the mass was determined to have invaded the head and body of the pancreas, and the clinical stage was T4bN1M0, stage IIIB (Union for International Cancer Control (UICC)). The patient was diagnosed with unresectable gastric cancer, and chemotherapy with S-1 and paclitaxel was initiated. Oral S-1 (80 mg/m2) was administered for two weeks, and intravenous (IV) paclitaxel (60 mg/m2) was administered on days one and eight. The patient received three cycles of this regimen at 14-day intervals and showed side effect of fatigue (grade 2 based on common terminology criteria for adverse events). Assessment of the patient's response to chemotherapy after the third course of treatment showed a remarkable reduction in tumor size by gastrointestinal endoscopy (). Abdominal CT showed decreased thickness of the gastric wall and a more distinct border between the pancreas and stomach (). Based on these findings, laparotomy was conducted. A weak adhesion was found between the stomach and pancreas during the procedure, but curative surgery was possible. Following the laparotomy, a distal gastrectomy was conducted. The patient's postoperative course was uneventful and he was discharged 20 days after surgery. The patient received adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year without any side effects. He lived for five years after surgery without recurrence.
The gross appearance of the resected specimen showed an ulcerative lesion 3 cm in diameter at the antrum of stomach (). Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes (). Fibrosis with marked lymphocytic infiltration was seen in the ulcerative lesion.


A previously fit and well 20-year-old Moroccan man presented with a right orbital tumor measuring 2 cm in diameter that had been rapidly increasing in volume. A complete resection of the tumor was made. The diagnosis was made on histological examination, confirming the orbital tumor to be an embryonal rhabdomyosarcoma.
The patient received six cycles of adjuvant chemotherapy with alternating vincristine, adriablastine and cyclophosphamide(VAC). One year later, the patient developed a local recurrence. Exenteration was performed,followed by treatment with six cycles of ifosfamide plus etoposide (IE); local radiotherapy was also given at a dose of 45 Gy. However, after 6 months, the patient developed a cutaneous mass in the right lumbar region, which was resected. A computed tomography - scan of the thorax, abdomen and pelvis did not reveal any metastasis. Macroscopically, the tumor size was 4 × 4 × 2.2 cm; the cut surfaces were nodular and fleshy; there was no necrosis and the edges showed an infiltrative pattern. Histologic sections with microscopy showed a proliferation of undifferentiated round cells arranged in sheets with some tapered eosinophilic cytoplasm. High mitotic rate was seen. The tumor cells infiltrating the subcutaneous tissue. Hematoxylin and eosin stained sections revealed loosely arranged round cells with large hyperchromatic nuclei and rare strap cells with eosinophilic cytoplasm (Figures and ). Immunohistochemical studies were performed using antibodies directed against desmin,myogenin, cytokeratin and leukocyte common antigen(LCA).
Photomicrographs showing a sheet of undifferentiated round cells. The tumour cells were immunopositive for desmin (Figure ) and myogenin (Figure ), and negativity for cytokeratin and LCA. A final diagnosis of cutaneous RMS metastasis was made. The patient then was treated by chemotherapy with 6 cycles of IE. He is still living 9 months after the initial diagnosis of skin metastasis with no recurrence.


An 18-year-old female Papillon (weight, 3.2 kg) was referred to the Yamaguchi University Veterinary Teaching Hospital (Yamaguchi, Japan) in April, 2010 for evaluation of a right forelimb tumor (). Surgical excision of the tumor had been performed twice previously, however, the tumor had recurred. Histological analysis revealed that the tumor was a rhabdomyosarcoma. On initial examination, the caudal right forelimb was covered by the tumor and the animal was incapacitated in the affected limb. The risk of recurrence and the treatment options were explained to the owners, which included surgery, radiation therapy and chemotherapy. Complete surgical excision was considered to be too complex, as the tumor border was unclear. HTH experimental therapy was recommended and the animal was enrolled in the clinical trial, with the owners’ written informed consent. A tissue ablation device for veterinary medicine (AMTC 200; AdMeTech Co., Ltd., Ehime, Japan) was used to administer the HTH treatment. On day 0, HTH therapy was performed with no anesthesia or sedation. Three needles of the device were inserted into the tumor tissue at 6-mm intervals and the HTH therapy was performed for 10 min at 65°C. On day 21, the tumor volume had decreased from that which was observed on day 0, and the subject had regained improved function of the limb (). Following four weeks of HTH therapy, the tumor disappeared.


A 14-year-old male Golden Retriever (weight, 32.7 kg) was referred to the Takagi Animal Clinic (Saijo, Japan) in February, 2011 for the evaluation of a tumor surrounding the anus (). Biopsy and histopathological analysis identified the tumor as a perianal gland adenocarcinoma. The risk of recurrence and the treatment options were described to the owners, which included surgery, radiation therapy and chemotherapy. Complete surgical excision was considered to be too difficult, as the tumor border was unclear. HTH experimental therapy was recommended and the animal was enrolled in the clinical trial, with the owners’ written informed consent. On day 0, HTH therapy was performed under general anesthesia, which was administered by inhalation of isoflurane. Five needles of the device were inserted into the tumor at 1-cm intervals, and HTH was performed for 10 min at 65°C () and repeated one additional time. On day 21, the tumor volume had decreased from that which was observed on day 0 (). HTH therapy was repeated using the same protocol, however, the dog succumbed one week later due to old age.


A 13-year-old male English Cocker Spaniel (weight, 12.3 kg) was referred to the Takagi Animal Clinic in February, 2011 for the evaluation of a tumor in the right external auditory canal (). A right total ear canal ablation was performed and subsequent histopathological analysis revealed a ceruminous adenocarcinoma. Two months after the intervention, the tumor recurred at the surgical site. The risk of recurrence and the treatment options were explained to the owner, which included surgery, radiation therapy and chemotherapy. Specifically, surgery presented the risks of vestibular disorders and facial paralysis. HTH experimental therapy was recommended and the animal was enrolled in a clinical trial, with the owner’s written informed consent. On day 0, HTH therapy was performed under general anesthesia, which was maintained using inhaled isoflurane. Five needles of the device were inserted into the tumor and HTH therapy was performed for 10 min at 65°C (). On day 22, the tumor volume had decreased from that which was observed on day 0. On day 28, the HTH therapy was repeated using the same protocol. On day 78, the tumor volume had decreased further and a third HTH procedure was performed. On day 133, the tumor had disappeared and did not recur.


A 50-year-old female was admitted to the Department of Endocrinology and Metabolism, Shaoxing People’s Hospital (Shaoxing, China) due to weight loss over a period of nine months. The patient had no previous history of hypertension or diabetes and no family history of paraganglioma. On admission, the patient did not exhibit proptosis. A physical examination revealed palpable thyroid nodules (size, 1.0×1.0 cm) with a medium texture, clear boundaries and the nodules were moving freely during swallowing. Furthermore, no enlarged neck lymph nodes were palpable. Auxiliary examinations, including a chest X-ray, electrocardiogram, gastroscopy, blood glucose testing, cancer screening panels, thyroid function panels and parathyroid hormone measurements, did not reveal any abnormalities. However, an ultrasound scan identified multiple bilateral thyroid nodules and a hypoechoic mass in the left side of the neck, which was considered to be a neurogenic tumor (). Plain and enhanced CT scanning revealed a soft tissue mass in the left posterior side of the thyroid (). The patient was transferred to the Department of Breast and Thyroid Surgery (Shaoxing People’s Hospital, Shaoxing, China) following identification of the thyroid nodules and a hypoechoic mass in the left side of the neck. Bilateral partial thyroidectomy combined with a resection of the left neck mass was performed under general anesthetic. During surgery, multiple solid, encapsulated masses of varying sizes (diameter, 0.5–1.0 cm) were observed in the two sides of the thyroid; a pale red solid mass (size, ~2.5×2.0 cm) with a rich blood supply was identified posterior to the middle and lower poles of the left thyroid gland, which bled and shrank following compression. The encapsulated mass had a gray/red appearance along the resected surface, without adherence to the left thyroid or adjacent vessels, and was located deep in the prevertebral fascia. Intraoperative analysis of frozen sections of the mass revealed a nodular goiter with fibrotic nodules; the left neck mass was considered to be a paraganglioma (size, 2.4×2.2×1.2 cm). The surgery was successfully completed and postoperative recovery was uneventful with no complications. Light microscopy (DM3000; Leica, Manheim, Germany) revealed that the tumor consisted of epithelial main cells in a nest-like structure on a paraffin-embedded section, which were separated by enlarged fibrovascular stroma (). Supporting cells were observed surrounding the tumor and reactive hyperplasia was observed in three lymph nodes. Pathological diagnosis confirmed nodular goiter with interstitial collagen and paraganglioma in the left side of the neck. Immunohistochemical analysis revealed that neuron-specific enolase (NSE), S-100 supporting cells, vimentin, smooth muscle actin blood vessels, synaptophysin (Syn) and chromogranin A (CgA) were positively stained (), while cytokeratin, DM, epithelial membrane antigen (EMA), Ki-67, nuclear factor, myelin basic protein and p53 were negatively stained (). The postoperative recovery was uneventful and follow-up enhanced abdominal CT and adrenal ultrasound examinations identified no abnormalities. The patient was followed up for 12 months and her condition was considered to be very satisfactory.


A 47-year-old man, with no past medical history, suddenly complained of headaches, without fever, vomiting and altered consciousness on February 10, 2012. He was admitted to a nearby clinic, but it was useless and the headache got aggravated, following hyperpyrexia. To strive for better treatment, he got admitted into the neurology department of a superior hospital. After admission, there were apparent cognitive deficits, namely: disorientation, short attention span, and gradual disordered consciousness which progressed into coma. A magnetic resonance imaging (MRI) of the brain was unremarkable. Examination of cerebrospinal fluid and cerebrospinal fluid cultures were negative, so he was then treated for presumed viral encephalitis. According to the profile, results of blood test and imaging evidence, the patient was treated with antiviral therapy, antiepileptic therapy and empirical antibiotics within 30 days period of coma. After this period of 30 days under coma, his mental state and speech improved with vigorous and effective treatment, but the ambulation did not improve significantly. Therefore, he had difficulty using his lower extremities.
From then on, he consulted with several doctors from time to time regarding the stiffness of both the hips and knees, but the condition of his lower extremities did not improve. Ten months after the onset of the coma, he came to our department of orthopedics in order to pursue natural movement. Both hips and knees were stiff and the clinical evaluation revealed the following passive ranges of motion of hips and knees as showed in the Table below. All other joints were normal.The patient’s laboratory findings were normal except for a slight increase in erythrocyte sedimentation rate (ESR) (24 mm/h; normal, 0-15 mm/h). Radiographs of the pelvis showed para-articular HO on the interior aspect of both femoral necks (Figure ). Anterioposterior and lateral radiographs of knees (Figure ) showed HO on the peripheral areas of knee-joints, especially on the medial. Lesions of four joints were also clearly showed in radiographs of both lower extremities (Figure ).
After admission to our institution, the patient and his family received pre-operation counseling, including the explanations of the available management options, expected outcome and possible complications. After extensive discussion of the risks and benefits of revision surgical excision of HO resection and concomitant peri-operative pharmacotherapy of Celecoxib for decreasing the risk of HO recurrence, the patient and his family agreed to proceed with the procedure as discussed. On December 5, 2012, he underwent the first operation: Revision surgical excision of the heterotopic bone of both knees was performed. In the surgery, an osteotome was used to excise the ossific mass in sufficient amount to free the joints and the medial collateral ligaments of both knees had degeneratively changed. Therefore, the reconstruction of the medial collateral ligament was applied. One month later, he underwent another revision surgery of excision of the heterotopic bone of both hips. The patient tolerated the surgical procedures well. After operation, the patient was given 200 mg Celecoxib orally once a day for a total of 8 weeks postoperatively. Postoperative radiographs of both knees showed that most of heterotopic bone of both knees had been excised (Figures and ). At the last follow-up visit, 18 months after the operation (is 28 months after the coma), he had no pain and could walk independently. The passive ranges of motion of hips and knees had significantly improved and the detailed information can be seen in above chart (Table ). On review of X-ray, there was no recurrence of HO and no loosening of rivets used in the reconstruction of medial collateral ligament (Figures and ).
HO is a rare and potentially detrimental complication of soft-tissue trauma, amputations, central nervous system injury (traumatic brain injuries, spinal cord lesions, tumors, encephalitis) [,], vasculopathies, arthroplasties and burn injury, characterized by lamellar bone growth in non-osseous tissues such as the muscle and the joint capsule. After brain or spinal cord injury, trauma, neurologic disease or injuries, or hereditary disease, HO may occur []. HO associated with viral encephalitis is very rare []. The occurrence of excessive, symptomatic heterotopic ossification around bilateral hips and bilateral knees is rarely described in the literature. Our report demonstrates heterotopic bone arising from periarticular region of both hips and both knees in a patient who suffered one month prolonged coma following encephalitis. To the best of our knowledge, this is the first report of HO in both hips and both knees following encephalitis. Under reviewing literature, we made a simple chart (Table ) below to show distinctions between patients who suffered multiple-joint following encephalitis. Daily functions of heterotopic ossification patients can be hampered by pain, inflammation, reduced mobility, the loss of normal posture and other complications []. Research so far reveal that the management of HO is controversial. As supported by the successful outcome in the present study, we recommend considering HO resection in conjunction with peri-operative pharmacotherapy of Celecoxib. In our current case study, the patient suffered stiffness of hips and knees and his family received pre-operation counseling, of which on December 5, 2012 he underwent the first operations. In order to free the both knee joints, We removed sufficient ossific mass and reconstructed the medial collateral ligament, This is the significant difference to other reported cases in literature which can also make the joint more stable. One month later, he underwent another revision surgical resection of the heterotopic bone of both hips. The patient tolerated the surgical procedure well. After operation, the patient was given medical treatment of 200 mg Celecoxib orally once a day for a total of 8 weeks. He had no recurrence of HO and no loose rivets for 18 months after the surgery with a significantly improved ranges of motion of hips and knees described in detail above.
The mechanism and pathophysiology which can lead to HO formation is still not fully understood. And molecular mechanisms of HO have not been fully elucidated. Many studies showed that primitive mesenchymal cells differentiate into osteoblasts which would lead to HO formation and the origin of these mesenchymal cells and the stimulus are poorly understood []. Gannon FH et al. discovered that inflammation first occurs in response to stimulations, including surgery, trauma and viral illnesses []. Inflammatory and skeletogenic signaling pathways are also supposed to play critical roles in HO formation. Bidner SM et al. [] proposed that failure of control in the immune system, central nervous system or indigenous inflammatory response lead to the release of inducing agents, resulting in HO formation. Urist [] et al. discovered that demineralized bone matrix can induce the formation of HO. They also presented bone morphogenetic protein as the true inductor. Ho SSW [] et al., recently put forward that Prostaglandin E2 is a transmitter to promote the original cell differentiation. Chalmers J [] et al. proposed that the following three requirements are necessary for HO formation, namely: inducing agent, osteogenic precursor cell and an environment which is permissive to osteogenesis. Once these conditions are meet, mesencnchymal cells are recruited, which then proliferate and differentiate into chondrocytes and/or osteoblasts, and ultimately lead to ectopic bone formation []. Botolin et al. [], also put forward that both the reaming debris and the extent of traumatic intraoperative injury to the surrounding soft tissues at the operative site play important roles in the development of HO after antegrade reamed femoral IMM in their case study. Several studies also have demonstrated that the low-oxygen tension [] and neurotransmitters are involved in the process of HO formation. Glrland DE et al. [] told us that prolonged coma, mechanical ventilation, spasticity and limited extremity movements may be the initiators of neurogenic HO. Although the pathogenic mechanism of HO remains unclear, functional immobility has been reported to be a risk factor []. Therefore, it is obvious that further studies for the mechanism and pathophysiology of HO are required.
It is also difficult to ascertain when the HO formation begins accurately, because the subject of HO formation has no specificity [] and lacks a reliable method for early diagnosis. Atypical early clinical performance of HO are the causes of hard distinction from cellulitis, osteomyelitis, thrombophlebitis and tumor. Without early detection or intervention, progression of HO can lead to severe long-term effects, including restricted joint mobility, severe pain and nerve entrapment. In the aspect of biochemical markers, alkaline phosphatase (ALP) has some certain clinical significance of early diagnosis of HO [], but ALP has no specificity. Therefore, it is difficult to determine the onset of HO, including HO following encephalitis in using biochemical markers. HO at different stages shows different imaging characteristics. Someone thought magnetic resonance imaging (MRI) is the best effective method for the diagnosis of early ectopic ossification, whiles X-ray and computed tomography (CT) can be used for review. Practice literature reports tell us that X-ray can not discover HO until 4–6 weeks later []. While some literature show that the most sensitive imaging modality for early detection of HO is three-phase bone scintigraphy which can also monitor the metabolic activity and degree of maturity of HO [,]. Although radiographic techniques such as computed tomography and magnetic resonance image provide high detailed anatomic representation of late stage HO, these modalities cannot detect early stages of HO. In summary, current imaging modalities, including CT, MRI and three-phase bone scintigraphy through helpful in late diagnosis are inadequate to help clinicians detect early HO development. The formation of HO begins within days to weeks of the inciting event. The disease has already spread beyond the point where it can be treated and impeded with oral medications, once visible through these current techniques. That is to say, none of the available prophylactic measures would affect the outcome of HO once the process begun []. Therefore, a urgent need exists to improve the current diagnostic modalities for HO which are inadequate to diagnose and intervene on HO at early time-points. Many researches showed that Roman Probe propelled non-invasive, transcutaneous evaluation of heterotopic bone formation. Petrson JR [] et al. also suggested that Roman Spectroscopy allowed for detection of HO formation as early as 5 days in mice following a burn injury. Hence, we should try hard to develop novel screening techniques to visualize and detect the onset and progression of HO with high sensitivity and specificity.
Numerous treatment options, including pharmacotherapy (such as: non-steroidal Anti-inflammatory drugs (NSAIDs) [], disodium etidronate (EHDP) et al.), motortherapy, radiotherapy, surgical therapy et al., are available but decision on which modality to choose depends on a detailed and accurate assessment of the disease process. NSAIDs were recognized as the most effective drugs to prevent the formation of HO after operation of acetabulum fracture []. Most doctors agree that indomethacin is the best choice among NSAIDs not only prevent HO but also slows down the process of HO development. However, the application of NSAIDs is relatively limited, for its adverse drug reaction such as gastrointestinal ulceration, decreased platelet aggregation and renal toxicity. Coventry MB [] et al. conducted a research with patients who had HO following total hip arthroplasty, and they believed that radiation aids to prevent the formation of ectopic bone. However, the potential side effect that we should consider is carcinogenesis. Despite the risk that it can trigger another round of HO, surgery remains the only treatment option to date once bone tissue has formed. To increase the range of movements of the joints and improve function and quality of life, surgery was a good choice among treatments. Therefore, we choose the method of revision surgical resection in our case study.
However, it is difficulty to decide when the best time is for the revision surgical resection of HO? Many researches have indicated that there is a need to wait for the heterotopic bone to matured before the procedure is undertaken. Garland et al. suggested that it requires 18-month before surgical excision in order to allow the bone to mature []. And most scholars recommended a minimum wait of 1 year after ectopic bone formation ahead of surgical excision []. Garland DE recommended that HO resection should be performed at different time intervals according to the HO aetiology: traumatic HO should be resected at 6–9 months, spinal cord injury at 1 years and traumatic brain injury HO at 1.5 years []. Serum alkaline phosphatase (ALP) is an important factor we should use to determine the timing of HO resection. Though the maturity of heterotopic bone is difficult to evaluate, it is also important to prevent the high recurrence rate relevant to excision of immature ectopic bone []. Recurrence is also an important complication of HO which should be considered after excision. The risk of recurrence is higher in patients undergoing multiple operations sequentially [] and it is found out that the risk of recurrence HO was high if the three or more joints were involved []. Botolin et al. supposed that diligent intraoperative care of the soft tissues and copious fluid irrigation with saline in the procedure of revision surgery appear to decrease the recurrence rate []. In order to free the stiffness in joint because of HO, it is necessary to remove sufficient ossific mass but complete excision is not necessary. And to decrease the recurrence rate of HO, active exercises should begin after the first postoperative week [].
In summary, as major treatment options discussed above have negative side effects to some extent, it is important to evaluate the risk of individual patients, and provide safe and effective treatments for them. Further studies for the mechanism and pathophysiology, the early diagnosis and optimal managements of HO following encephalitis are required.


The patient was a 17-year-old female high school senior who was brought to our department with complaints of “rambling and incoherent speech, running away from home, and believing that her family members were actually imposters trying to persecute her.” Upon questioning it was revealed that her complaints started three years ago and continued without remission and that she was hospitalized twice for a total of 51 days with a diagnosis of schizoaffective disorder. She was treated with risperidone 6 mg/day, quetiapine 300 mg/day, and valproate 750 mg/day for varying durations but her compliance was poor and there was no benefit from drugs. The complaints increased a month before her last application. Family history revealed that her mother was diagnosed with schizoaffective disorder and died after a suicide attempt fifteen years ago and that her maternal uncle was diagnosed and treated with psychotic disorder, not otherwise specified. The patient was promptly hospitalized for differential diagnosis and treatment. Baseline mental status examination showed reduced grooming and excessive suspiciousness. Mood and affect were irritable. Speech was pressured. Thought processes were incoherent and the content was bizarre. She reported that other people replaced her family and that her “true” family was in another city (Capgras syndrome), that her father had 250 wives but she knew only one of them, that the hospital in which she was being evaluated was in another city (reduplicative paramnesia), that her father was trying to harm her (persecutory delusion), that ward personnel, nurses, and other patients regularly change places between themselves and with objects (intermetamorphosis), that one of the nurses changed places with her via “magic” and their physical features changed as well (reverse-intermetamorphosis), that her reflection in the mirror was actually that of another girl, resembling herself (misidentification of reflection), and that her father was actually God (grandiosity). Psychomotor activity was increased while insight was lacking.
Psychometric evaluations revealed scores of 107 (positive: 36, negative: 23, and general psychopathology: 48) and 24, respectively, from Positive and Negative Syndrome Scale (PANSS) and Mini-Mental Status Examination (MMSE). She was noted to have problems in copying figures and doing calculations and in immediate recall. Visuomotor evaluation with Bender-Gestalt test revealed an error score of 9 points. Physical and neurological examinations and laboratory evaluations including toxicology screen were normal. Crainal MRI and EEG were within normal limits. As a result, the patient was diagnosed with schizoaffective disorder-manic type according to DSM-IV-TR criteria. Due to low compliance the patient was started on parenteral risperidone 37.5 mg/every 15 days. Risperidone 6 mg/day and valproate 750 mg/day orally were continued until the 3rd week. During hospitalization the patient refused meetings with her family while she had no problems in receiving telephone calls from them. Evaluation at the 6th week of hospitalization revealed a PANSS score of 65 (positive: 21, negative: 15, and general psychopathology: 29) and a MMSE score of 27. She was noted to have problems in figure copying and doing calculations while her immediate recall was normal. A repeat of Bender-Gestalt test revealed an error score of 5. The patient was discharged on the 60th day with a treatment regimen of parenteral risperidone 37.5 mg/every 15 days.


A 62-year-old woman presented with complaints of decrease in vision and myodesopsia in her left eye of 1-month duration. There was no relevant ocular or medical history. She had no history of hypertension, hyperlipidemia, and diabetes mellitus. Her best-corrected visual acuity (BCVA) was 1.5 in the right eye and 0.6 in the left eye. The intraocular pressure was 10 mmHg in both eyes. Slit-lamp examination of both eyes and fundus examination of the right eye were unremarkable.
Fundus examination of the left eye disclosed an elevated, round, and reddish lesion and a retinal hemorrhage at the superior aspect of the optic disc. In addition, there were retinal opacification along the superior branch retinal artery and a small vitreous hemorrhage (). Spectral-domain optical coherence tomography (SD-OCT) showed a serous retinal detachment involving fovea and marked elevation of the retinal surface in the reddish lesion (Figures and ). The SD-OCT map of the retinal thickness showed a thickening extending from the parapapillary region to the macula (). Fluorescein angiography (FA) showed incomplete perfusion of the superior branch retinal artery indicating the presence of a BRAO (). Because visual field tests were not performed, a presence of visual field defect corresponding BRAO was uncertain. The vascular loops could be seen on FA but did not show any dye leakage even in the late phase of FA. Indocyanine green angiography (ICGA) demonstrated the prepapillary vascular loops and a round hypofluorescent area with hyperfluorescent margins (). These findings suggested the presence of a macroaneurysm. The lack of filling of the aneurysm-like round dilatation suggested a blockage of the lumen with a thrombus which was considered to be associated with the BRAO. However, communication with the aneurysm-like dilatation and the retinal artery was unclear.
A diagnosis of prepapillary vascular loops complicated by a suspected macroaneurysm rupture and BRAO was made. One month after the initial presentation, IVB was performed because the serous retinal detachment persisted. This was an off-label use of bevacizumab, and the procedures were approved by the Institutional Review Board of Tokushima University Hospital. The procedures used for the treatments conformed to the tenets of the Declaration of Helsinki, and an informed consent was obtained from the patient after the benefits, potential risks, and alternative treatments were discussed. One month after IVB, the BCVA improved to 1.0. Fundus examination disclosed venous and arterial prepapillary loops with spiral turns, a slightly organized, yellowish-white lesion at the superior aspect of the optic disc, and hard exudates around the macula (). SD-OCT showed a resolution of serous retinal detachment ().
One year after the initial presentation, the patient maintained a BCVA of 1.0 in the left eye, and fundus examination disclosed a completely organized, white macroaneurysm. FA clearly showed venous and arterial prepapillary loops with spiral turns (). Fine collateral vessels (dilatation of retinal capillary vessels) were seen at the superotemporal aspect of the optic disc. ICGA showed a cilioretinal artery () and no aneurysm-like lesion at the superior aspect of the optic disc ().


A 22-year-old Caucasian woman who was a student presented to our neuro-otology clinic on two separate occasions five years apart. Her initial symptoms were a six-month history of intermittent right-sided tinnitus and bilateral hyperacusis (abnormal sound sensitivity arising from within the auditory system to normal or moderate-level ambient noise which would not trouble other people). She also reported right ear fullness and significant difficulty hearing in background noise when stressed.
Otoscopy, a neuro-otological examination, pure-tone audiometry, tympanometry, stapedial reflexes, oto-acoustic emissions (OAEs), auditory brainstem response and speech audiometry results were normal. She had particularly strong transient OAE responses and spontaneous OAE activity bilaterally. This was consistent with increased cochlear gain, suggestive of reduced efficacy of inhibitory feedback in the auditory system. Several sessions of auditory rehabilitation were carried out with a hearing therapist, involving counseling, communication tactics, tinnitus and hyperacusis retraining, advice regarding ear-level noise generators to enable desensitization, relaxation techniques and stress management. Her symptoms had greatly improved at review nine months later, and she was discharged.She was referred again to our clinic by her general practitioner five years later. Her primary complaint was recurrent one-hour episodes of painful cutaneous erythema of the right external ear (Figures and ) that was associated with severe right temporal pain radiating down to the mastoid area with transient subjectively reduced hearing, right conjunctival injection, intolerance to noise and light, which was exacerbated during these episodes; the latter symptom was suggestive of involvement of pathways outside the auditory pathway.
These symptoms caused our patient considerable distress, resulting in weekly attendance for three months at her general practitioner’s clinic, in addition to presentation at the local emergency departments and to ear, nose and throat clinics, prior to referral to our department. During the previous three months, she had also experienced continuous headaches and fatigue with occasional light-headedness during episodes of erythematous ear. She reported no nausea, visual field symptoms, tinnitus or vertigo.
Differential diagnoses of dermatological, temporomandibular joint, dental, pharyngeal and cervical problems were excluded on the basis of a head and neck examination. On inspection, there was no evidence of erythema or of infection in the ear or mastoid area. The otoscopy findings were normal. A neuro-otological examination was unremarkable, including extra-ocular eye movements, cranial nerves, cerebellar function and clinic room balance tests. Pure-tone audiometry and tympanometry showed normal hearing and middle-ear function. Magnetic resonance imaging of the brain was normal. Routine blood tests were negative. She was diagnosed with RES associated with hyperacusis.
She was reassured that she had no major structural pathology. There were some migrainous features in her medical history. Management of her migraine included starting behavioral modifications, such as reducing caffeine intake, stress reduction, optimizing fluid intake, improving sleep pattern, relaxation techniques and starting exercise. She was advised to keep a symptom diary to identify further triggers. She was offered migraine prophylaxis but declined it.
On review after four months of supportive measures, she was feeling much better, with complete resolution of her headaches and much reduced frequency of episodes of erythematous ear. She reported absence of pain in the ear and less sensation of swelling. Triggers for red ear episodes identified from her symptom diary included stress and, surprisingly, orange juice. Her symptoms were managed successfully without medication for four years.


A 33-year-old Chinese woman presented to the gynecology clinic complaining of vaginal bleeding without abdominal pain. Her last menses was 42 days before the visit. She used no form of contraception. Our patient had no history of PID, no prior IUD, no use of fertility drugs and no pelvic surgery. Our patient had had conservative treatment in our hospital due to a left tubal pregnancy eight years before (a single-dose methotrexate (MTX) injection (50mg/m2) was administered, and she had an uneventful decrease in serum β-human chorionic gonadotropin (HCG) levels within two weeks) and one spontaneous abortion two years before. A physical examination revealed stable vital signs: blood pressure of 107/55mmHg and a pulse rate of 88/min. Her abdomen was soft and nontender. A vaginal examination revealed bloody discharge and a nontender pelvis. Her serum level of β-HCG was 6993.1IU/L and her progesterone level was 13.40μg/L. No gestational sac was detected in the uterine cavity by transvaginal ultrasound (TVUS) scan on 12 December 2013.The presumptive diagnosis of ectopic pregnancy was made and our patient was admitted to our gynecology ward. Upon admission, her serum level of β-HCG increased to 13721.3IU/L. A 45mm×29mm right adnexal mass was found by TVUS examination (on 13 December 2013) (Figure ), and an ectopic pregnancy was suggested. Nothing abnormal was detected in the left adnexal area. The endometrial thickness was 10mm and the uterine cavity was empty. Having discussed the pros and cons of medical and surgical treatment options before the surgery, our patient and her family preferred the surgical treatment, and she insisted that she would like to preserve the integrity of the tube. After informed consent was obtained, a laparoscopy was performed, which revealed a 40×50mm nearly ruptured mass in the interstitial part of the right tube (Figure ). A wedge resection of the right side of the uterine horn and partial (isthmus) resection of the right fallopian tube were done. An inspection of the left tube showed it was slightly thickened, which was considered to be a inflammatory sign because of the left tubal pregnancy eight years before. Pathology results confirmed placental villi in the right tube.Her serum level of β-HCG was 7373.5IU/L on the first day after surgery and increased to 10522.3IU/L the next day. On 16 December 2013, an ultrasound scan showed a 24mm×14mm anechogenic image in her left fallopian tube, mild thickened endometrium, and a small amount of fluid collection in the Douglas Pouch (Figure ). Our patient had no obvious discomfort after the surgery so that the expectant therapy was executed.On 18 December 2013, her serum level of β-HCG rose to 13721.3IU/L and her progesterone level was 8.94μg/L. A 26mm×16mm left adnexal mass and a small amount of fluid was detected on TVUS examination. The endometrial thickness was 11mm and the uterine cavity was empty (Figure ). Our patient was considered for BTP. A laparoscopy was performed after informed consent was obtained. A 30×20mm unruptured left ampullary ectopic pregnancy was found (Figure ). A left linear salpingostomy and curettage were performed. Pathology results confirmed placental villi in the mass of the left tube and that there were no placental villi in the curettage specimen. Our patient was discharged home two days after surgery, in good condition. Her β-HCG serum level was 4128.0IU/L when she left hospital. She was followed up until her β-HCG serum level was normal.


A 28-year-old Indian male patient presented with right knee swelling for one and a half year associated with severe pain and inability to bear weight on right lower limb. The onset of the swelling was associated with low grade continuous fever for six months which used to subside with anti-pyretics to recur again. Radiographs of the right knee did not reveal any significant joint or bony pathology. The patient was empirically advised to take oral amoxicillin-clavulanic acid 625 mg thrice a day along with low dose steroid 5 mg prednisolone once a day by a local practitioner for one month but there was no relief in knee pain or swelling. He was further subjected to chest radiography in which a cavitatory lesion was noticed in upper lobe of left lung. Tuberculosis is an endemic condition in India and suspecting the same he was prescribed anti-tubercular therapy (4 drug regimen - isoniazid, rifampicin, pyrazinamide and ethambutol). Within a week of starting antitubercular therapy, his fever subsided but at the same time he developed rashes all over his body associated with itching. The symptoms were attributed to pyrazinamide hypersensitivity reaction. The anti-tubercular drugs were stopped for five days and symptoms were managed with oral levo-cetrizine. Pyrazinamide was then excluded from regimen and he was asked to continue rest of the medication. He took antitubercular drugs for seven months but there was no decrease in the knee pain and swelling. Approximately seven months after the start of antitubercular treatment, he had an episode of generalised tonic clonic seizure which was managed with tablet levetiracetam. He was then advised to undergo magnetic resonance imaging (MRI) of the brain. It revealed frontal lobe masses bilaterally which were hyperintense on T2 and hypointense on T1, the right one measured 2.9 × 2.4 × 2.7 cm and the left one measured 2.2 × 2.2 × 1.9 cm. It was again presumed to be a manifestation of disseminated tuberculosis because of endemicity of tuberculosis in the region and its focus was considered to be from the knee joint and left lobe of the lung. Subsequently, amikacin and moxifloxacin were added in the anti-tubercular regimen suspecting it to be a case of multi-drug resistant tuberculosis. There was no change in the knee swelling, moreover a swelling appeared in the right proximal leg close to knee joint after ten months of antitubercular therapy. He again had two episodes of generalized tonic clonic seizure after eleven months of anti-tubercular therapy. Subsequently, phenytoin was added to his treatment for seizures along with antitubercular drugs. Keeping in mind drug interactions between rifampicin and phenytoin, serum phenytoin levels were done and thedrug dosage was adjusted. Following this he presented to the orthopaedic outpatient department of our institute with complaints of right knee pain and swelling extending to right leg. There was no prior history of any invasive procedure (biopsy or aspiration) done on the right knee.On examination, he appeared lethargic and was afebrile. His systemic examination including the chest was unremarkable. He had a smooth, soft, fluctuant, tender, moderately warm, well-defined swelling of size 7 × 5 cm on the anterolateral aspect of the right knee and proximal leg (Figure ). The overlying skin was shiny. The local temperature was raised as compared to the contralateral knee joint. There was no neurovascular deficit.His total blood counts were in normal range with relative neutrophilia. Erythrocyte sedimentation rate by Westergren’s method was 90 mm/hour (normal range ≤ 20 mm/hour for males) and serum C-reactive protein level was 85 mg/litre (normal range < 6 mg/litre). The radiographs of the right knee demonstrated mild peri-articular osteopenia with global reduction in joint space along with soft tissue density around the knee joint (Figure ).Contrast enhanced MRI of the right knee joint revealed infiltrative peripheral enhancing lesion, which was hyperintense on T2 and hypointense on T1 sequences, in the lateral tibial condyle with conglomerate, lobulated similar signal intensity lesion in the overlying soft tissues, likely representing intra-osseous and extra-osseous abscesses with synovial inflammation involving the knee joint and the supra-patellar bursa (Figure ).Contrast enhanced MRI of the brain revealed large lobulated lesions, hyperintense on T2 and hypointense on T1, in bilateral frontal lobes with irregular heterogenous peripheral enhancement showing peripheral restricted diffusion and peri-lesional edema. Magnetic resonance spectroscopy showed elevated lactate levels in the lesions, likely representing fungal abscesses. There was slight increase in size of the lesion as compared to the previous scan (Figure A).Whole body positron emission tomography-computed tomography (PET-CT) scan demonstrated hypermetabolic cavitatory lesion in the upper lobe of left lung with associated ring enhancing lesions in the cerebrum (Figure B).
Contrast enhanced computed tomography (CECT) scan of the chest revealed an irregular, moderately thick-walled cavitatory lesion in the upper lobe of left lung with nodularity along the inner wall of the cavity at places and a rounded well-defined intra-cavitatory nodule along upper part of the cavity suggesting presence of disseminated aspergillosis (Figure ). This could also be explained by formation of tubercular cavitation initially followed by aspergillosis development inside. Costal aspergillosis due to contiguous involvement of ribs from the pulmonary focus has also been described in literature []. It was ruled out as the computed tomography (CT) scan was done using both lung and bone windows, and also due to absence of pleuritic pain, localised tenderness and swelling.
Biopsy was done from the right proximal tibia and the histopathology report revealed necrotic tissue with acute inflammatory exudate and focal giant-cell formation suggestive of osteomyelitis (Figure A). Presence of knee joint swelling along with the above findings suggested contiguous involvement of knee from the osteomyelitic focus causing septic arthritis. The cytopathology report from the intra-articular fluid demonstrated mainly acute inflammatory exudate and necrosis along with occasional giant-cells. The stain for acid fast bacillus was negative. Periodic acid schiff (PAS) stained tissue section showed stout septate fungal hyphae of Aspergillus species (Figure B). Methenamine-silver-stained tissue section also showed septate hyphae of Aspergillus species (Figure C). Galactomannan test was also positive in the intra-articular fluid suggesting presence of Aspergillus. The growth of Aspergillus flavus was seen on the fungal culture medium (Figure D).
A diagnosis of disseminated aspergillosis was made following the above investigations. Subsequently, he was put on oral voriconazole and intravenous amphotericin B (for 15 days), as this combination therapy is reported to be effective in invasive aspergillosis [], along with intravenous dexamethasone and knee arthrotomy was done. Femoral and tibial articular surfaces were found to have erosions with geographic hyper-pigmented lesions. Dead and necrotic tissue was debrided from the knee joint and thorough wash done. Biopsy samples sent from the bone as well as the synovium during arthrotomy confirmed the presence of Aspergillus flavus. Synovial fluid sent for culture also growed colonies of Aspergillus flavus on the fungal culture medium confirming it as a case of proven aspergillus arthritis. He had no recurrence of fever or seizures following the surgery and the knee swelling and pain subsided after 3 months of antifungal treatment with oral voriconazole.
Staphylococcus is the most common organism implicated in septic arthritis []. Fungal infections, especially Candida and Aspergillus, though rare have been found to occur more commonly in diabetics and immunosuppressed persons []. They lead to an opportunistic infection once there is decrease in the immunity of the body. As far as aspergillosis is concerned, it involves lungs, brain, kidneys, liver and gastrointestinal tract in majority of the cases []. Aspergillosis has also a predisposition for vertebrae and ribs [, ]. The hip joint is most commonly involved joint followed by knee, wrist and ankle among the cases of articular aspergillosis []. Aspergillus genus includes more than 35 species of saprophytic moulds among which Aspergillus fumigatus is the most common pathogenic organism [].
The diagnosis of Aspergillus osteomyelitis often requires more stringent measures than required in cases of bacterial osteomyelitis. The general accepted norm in its diagnosis includes repeated culture of the fungus from the diseased site along with histo-pathological examination demonstrating inflammatory exudates, giant-cell reaction and numerous branching fungal hyphae. These findings along with the clinical manifestations of the disease help in arriving at the diagnosis []. In cases of septic arthritis, the organism can be isolated from the synovial fluid and the total leukocyte cell counts are generally above 5000/mm3 associated with a relative neutrophilia. Aspergillus grows very fast and the cultures are usually visible in 2 to 4 days, though in some cases it may require a longer incubation period. The fungus is found extensively in the environment and infects almost each one of us but the clinical manifestations appear more commonly in immunocompromised cases. Although recent studies report that Aspergillus osteomyelitis can be seen in immunocompetent patients also, septic arthritis in such patients is still believed to be a rare entity and its pathogenesis is not known [, ]. In our case, neither the clinical features nor the investigation reports suggested any sign of immunosuppression.
The treatment of Aspergillus arthritis includes surgical drainage along with administration of antifungal agents like amphotericin B and voriconazole. There is, however, no consensus on the use of amphotericin B or voriconazole in the treatment of articular aspergillosis []. There is risk of nephrotoxicity with the use of amphotericin B so its maximum dose and duration should be stringently regulated. Voriconazole can be used in both intravenous and oral dosage form with lesser side effects as compared to amphotericin B.


A 25-day-old male patient presented with right inguino-scrotal swelling for 4 days. There was history of bilious vomiting for one day followed by progressive abdominal distension. He was reluctant to feed and had not passed urine for the last 24 hours. Baby was sick and irritable, with high grade fever and signs of dehydration. There was a 2cm x 2cm irreducible tender swelling in right inguino-scrotal region, the upper limit of which was not approachable. The swelling was not trans-illuminant and the testis was not palpable separately. Abdomen was distended and tense with no palpable mass. Bowel sounds were not audible. Radiograph abdomen showed multiple air fluid levels with a cutoff point in right lower abdomen. A provisional diagnosis of obstructed inguinal hernia was made.
Patient was resuscitated and explored. The right inguinal canal was opened through inguinal skin crease incision. On opening of sac, about 3-4 ml of pus was found along with the terminal ileum. On further exploration appendix was found to be perforated at its tip and caecum was hyperemic (Fig. 1). Right testis was viable. Appendectomy was done and contents of the hernial sac were reduced. High ligation herniotomy was done. Postoperative recovery remained uneventful.


A 33-year-old woman had cough and expectoration without fever or other discomfort. A peripheral blood count revealed an increased white cell count, but there was no obvious abnormal change on chest radiographs. Thus, the local physician attributed her symptoms to allergic bronchitis and she received anti-inflammatory treatment. However, she visited the hospital again after five months because of the same symptoms, which were accompanied by severe shortness of breath. Laboratory examination revealed increased white blood cells in the peripheral blood, but the absolute value of eosinophilic granulocytes was in the normal range. Other tests showed increased erythrocyte sedimentation rate (ESR), negative autoantibody, carcinoembryonic antigen far lower than the reference value, but a weakly positive Postscript Printer Description skin test. Chest radiography and CT scan revealed a space-occupying lesion in the upper lobe of the right lung, which indicated lung cancer with atelectasis of the right upper lung (Figure ) without nodal involvement. We performed bronchial mucosal biopsy and CT-guided percutaneous needle aspiration biopsy (aspiration biopsy), which revealed extensive eosinophil infiltration and no evidence of malignancy. Positron emission tomography scan and bone marrow biopsy were also normal. Repeated sputum cultures and parasite antigen testing excluded bacterial and parasitic infection, respectively. In addition, we did not find acid-fast bacilli from smears or bronchoalveolar lavage fluid (BALF), and the Mycobacterium tuberculosis (TB) DNA copy number from the BALF and lung biopsy tissues were all <25 copies/mL; therefore, we also excluded TB. The lesion was suspected eosinophilic granuloma, and the patient received an experimental glucocorticoid treatment that successfully alleviated her symptoms. However, subsequent CT scans revealed an increased mass, and the patient underwent biopsy again. While her bone marrow biopsy was normal, the ESR remained increased.


A 77-year old woman visited our clinic with a 1-month history of abdominal distension and discomfort. She had been diagnosed with coronary artery disease prior to this presentation. Physical examination showed ascites and firm/fixed mass in the suprapubic area. In the left supraclavicular area, nodular masses were palpable, raising suspicion of metastatic lymph nodes. Computed tomography (CT) revealed a huge heterogenous soft tissue mass in the pelvic cavity. Chest CT showed an extensive, conglomerated soft tissue density in the left supraclavicular area. The CA125 value was 124 u/ml. She underwent an exploratory laparotomy. At operation, a 15-cm ovarian mass was found to adhere to the uterus, bladder, rectum, and small intestine. About 500 ml of ascites was noted. The uterus, pelvic mass, and neck masses were removed, and there were large amounts of intraoperative bleeding. The pathologic diagnosis of the ovarian mass was undifferentiated non-small cell neuroendocrine carcinoma of the ovary. Immunohistochemical staining was negative for synaptophysin, but positive for chromogranin A and NSE (Figure ). The pathologic examination revealed that the neck mass had malignant cells with massive necrosis. The cytologic evaluation of the ascites showed malignant cells. She received 1 session of etoposide 100 mg/m2 for 2 days along with 1 session of carboplatin 300 mg/m2 at 14 days after operation. She died of septic shock after 45 postoperative days.


A 58-year old woman was referred to our clinic after being diagnosed with neuroendocrine carcinoma of the ovary at a private clinic. She had complained of abdominal discomfort for 1 month prior to this presentation and was found to have an ovarian mass. She had no remarkable past medical history or family history. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, and pelvic lymph node sampling at the private clinic. The pathologic diagnosis of the mass was undifferentiated non-small cell neuroendocrine carcinoma restricted to the left ovary. The surgical stage was Ia. She was treated with 6 sessions of a combination chemotherapy consisting of paclitaxel 175 mg/m2 and cisplatin 90 mg/m2. Five months after the last chemotherapy, a recurrent mass was noted around the para-aortic lymph node area by CT scan. It measured about 2.3 × 1.6 cm on the left para-aortic area. The CA125 level was 1.6 u/ml. She underwent secondary debulking operation. At the laparotomy, a 3-cm mass was noted in the left para-aortic lymph node. The mass was removed and histopathologically examined. The pathologic diagnosis of the mass was large cell neuroendocrine carcinoma recurrent in the para-aortic lymph node. She was treated with 7 sessions of taxotere 75 mg/m2 every 3 weeks. She died of multiple organ failure at 17 months after initial diagnosis.


A 67-year old woman was referred to our clinic because of an ovarian mass. She had visited a private clinic due to urinary frequency, and the ovarian mass was found by transvaginal sonography. At presentation, CT scan revealed a 13-cm multiseptated mixed solid and cystic mass in the left ovary which was suspected of cystadenocarcinoma. The CA125 level was 71.8 u/ml. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, para-aortic lymph node dissection, and total omentectomy along with multiple biopsy. At operation, the mass was composed of solid and cystic portions (Figure ). The pathologic diagnosis of the mass was neuroendocrine carcinoma of non-small cell type arising from the left ovary which involved the pelvic peritoneum. Immunohistochemical staining was positive for pancytokeratin, CD56, and pancytokeratin, and was focally positive for NSE; however, it was negative for synaptophysin and chromogranin A (Figure ). The surgical stage was IIb. She was treated with a combination chemotherapy consisting of paclitaxel 175 mg/m2 and carboplatin 4-hour area-under-the curve (AUC4) every 3 weeks. She is still healthy 5 months after operation.


A 75-year-old man presented with dysuria. Imaging revealed prostatic hyperplasia. Blood laboratory test showed mild PSA elevation of 7.6 ng/mL. No infections were seen. Other tumor markers were within normal ranges. Core biopsies of prostate showed no malignant cells. Next, he was found to have small grade 2 papillary urothelial carcinoma with mild invasion (stage pT1) in the bladder, and TUR-BT was performed. One year later, the patient was found to have atypical cells in urine by cytology. Cystoscopy revealed no bladder tumor, but enhanced CT showed irregular shadows in right kidney (). The diagnosis of radiologists and urologists was renal pelvic carcinoma, although renal parenchymal tumor was not excluded. The patient underwent open right ureteronephrectomy.
Grossly, the kidney specimens showed a solid white tumor measuring 1.4 × 1.6 × 1.8 cm in renal parenchyma (). Renal pelvis was free from tumors. The tumor was well defined from renal parenchyma. Five histological sections were taken from the tumor for microscopy and four sections from nontumorous kidney and pelvis.
Microscopically, the kidney tumor was well defined from renal parenchyma. The tumor was composed of relatively compact spindle cells tissue with mild inflammations and many necrotizing granulomas (Figures and ). Epithelioid histiocytes were abundant but giant cells were few. A mild degree of lymphocytes and plasma cells were seen. There were no features of dense collagenous, myxoid or vascular areas. The features suggested tuberculosis (TB), but Ziehl-Neelsen (ZN) stains revealed no signals. PCR technique for TB DNA, done twice, revealed no signals.
Scrutiny of body by imaging revealed no evidence of TB, and lungs were free from inflammation and tumor. Upper and lower gastrointestinal endoscopy showed no significant lesions except for a few adenomas of the colorectum. ZN stain and PCR for TB of bronchoalveolar lavage, done twice, showed no evidence of TB infection, and PCR of urine also showed no TB signals. Therefore, TB infection was not likely. No organ culture study related to the renal tumor was carried out because the samples were already fixed in formalin.
Immunohistochemistry, which was performed by envision method [–], of tumor showed that the tumor spindle cells were positive for vimentin, CD68 (), and Ki-67 (labeling = 18%). Moderate staining of α-smooth muscle antigen (ASMA) and neuron specific enolase (NSE) was noted in tumor spindle cells. Focal staining of KIT (mast cells), S100 protein (Langerhans cells), and CD10 (spindle cells) was present. The tumor spindle cells were negative for other antigens. The entrapped tubules were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK 7, CK18, CA19-9, and MUC1 and entrapped glomeruli for CD10. The vessels of tumor were positive for CD31, factor VIII-related antigen, and CD34. Immunostaining of CD3, CD20, CD38, CD45, CD45RO, CD56, CD57, CD79α, κ-chain, λ-chain, and CD138 revealed a few lymphocytes and plasma cells. Immunostaining of IgG4 showed few IgG4 containing cells. There were no immunoreactions for CK34BE12, CK5/6, CK14, CK8, CK19, CK20, CEA, EMA, p63, p53, ErbB2, chromogranin, synaptophysin, NCAM, MUC2, MUC5AC, MUC6, CDX-2, and myoglobin. The author diagnosed the tumor as IPT because the tumor was inflammatory in nature although histologic features were not typical.


A 30-year-old female, gravid 2 para 0, was referred to the Department of Ultrasound, Beijing Anzhen Hospital (Beijing, China), following a routine prenatal ultrasound examination at Cangzhou City Maternal and Child Care Service Centre (Cangzhou City, China) where pericardial effusion (PE) was detected. The patient had previously suffered a spontaneous abortion at 11 weeks of pregnancy two years ago and the reasons for this remained unclear. Two-dimensional (2D) and three-dimensional (3D) ultrasound imaging was performed using the Voluson E8 ultrasound system (4–8 MHz probe; GE Healthcare, Cleveland, OH, USA). The evaluation demonstrated a single live intrauterine pregnancy of 26 weeks. The fetal echocardiography four-chamber view assessment demonstrated a 6.3-mm thickening of the right atrial wall. Moderate PE was also observed. Color Doppler imaging indicated a narrow foramen ovale flow of only 1.9 mm in diameter (). A bicaval view revealed superior vena cava and inferior vena cava diameters of 3.0 mm and 3.4 mm, respectively. The patient was informed of the possibility of fetal abnormalities and asked to attend weekly follow-ups. However, the patient did not feel quickening two days later and fetal mortality was diagnosed by fetal echocardiography. An autopsy of the fetus revealed that the heart was slightly enlarged, with a subendocardial nodule of 4.3×4.0 mm in size located in the right atrium. The nodule was sharply demarcated, exhibiting a reddish-gray color with a moderately firm texture and the typical appearance of a rhabdomyoma (). Histological hematoxylin and eosin staining revealed nodular hyperplasia with clear boundaries, swirl-like cells, cords and a random orientation. The tumor cells possessed a strong eosinophilic cytoplasm, with slightly increased nuclear size and chromatin condensation. However, atypia was not evident (). The images were reviewed offline by tomographic ultrasound imaging (TUI) and spatio-temporal image correlation (STIC) imaging, which clearly displayed a 5.0×4.0-mm mass located in the right atrial wall area (). No major or minor manifestations of tuberous sclerosis or other notable family histories were documented.


The case is a 26 years old lady who had referred to a gynecologist because of infertility 2 years ago. She has married 8 years ago and after 2 years, she decided to have child. During the first two years of marriage they used natural method for contraception and she had not used any OCP or IUD. Her menarche was at the age of 14 and from then on she has a regular and normal monthly menstruation.
She had a negative past medical history with no sign or symptoms of neurologic diseases such as anxiety or depression. She had also no history of any clinical disease, pelvic or abdominal surgery, and extensive weight loss and drug or alcohol abuse.
In her family history the only positive clues were; the presence of hypothyroidism, diabetes and vitiligo in her mother and aunts. In physical exams: BMI=23, secondary sexual signs were normal and there was no sign or symptom of hirsutism, acne or any other systemic disease. Evaluation of her husband revealed normal male factor and spermogram. Laboratory findings included: serum FSH, serum LH, serum prolactin, TSH, testosterone, progesterone and estradiol which all of them were at the normal range.
Post coital test (PCT) and histrosalpangography were normal. Diagnostic laparoscopy showed no signs of tubal adhesion or endometriosis. After seven months and performing primary and secondary evaluation, she was diagnosed as a case of unexplained infertility and IVF was suggested for her.
About 9 months ago, the patient had a medical consultation because of diarrhea and 3 kg of weight loss. She reports a history of 12 months intermittent, non bloody and osmotic diarrhea which consists of normal bowel habits intervals. There was no history of fatty stool or consumption of laxatives.
Lab findings:
HB: 11.8 (NL: 12-16) MCV: 76 (NL: 80-95)
MCH: 27 (NL: 36-48) Serum Fe: 110 (NL: 80-180)
TIBC: 320 (NL: 250-460) Serum Ferritin: 54 ngr/ml (12-300) CRP: +ESR: 18 S/E: negative
OB: negative. AST: 29 IU (NL: 5-40)
ALT: 31 IU (NL: 8-40)
Considering iron deficiency anemia, intestinal signs and the history of 4 years infertility, we became suspicious to celiac disease and checked serological factors (total IgA and tTG).
The positive results of these tests (Total IgA>40 and tTG>30) followed by upper GI endoscopy and biopsy of the second portion of duodenum. The obtained tissues were observed by two expert pathologists and they reported severe malabsorption with flattening of villi, hyperplasia of crypts and total atrophy of mucosa which was presenting stage III of modified marsh classification ( and ). Based on patient's history and serologic and pathologic findings diagnosis of CD was confirmed and she received a complete gluten free diet. After 3 months all her clinical features including; diarrhea, flatulence and anemia were eradicated and pregnancy occurred.


A 5-year-old Turkish boy presented with a 3-year history of nasal obstruction. He was otherwise healthy and had no fever, recent cough, nasal discharge, or epistaxis. On physical examination, a pink soft tissue mass in his right nostril was visible. His nasal septum was completely deviated to the left side and there was slight nasal enlargement due to the mass. A needle aspiration from the mass revealed a clear fluid with shrinkage of the mass, indicating that the mass was a cystic lesion rather than a soft tissue one. Other head and neck region examination findings were normal. His white blood cell count was 11.5×103/mm3 (range: 4 to 10×103/mm3), hemoglobin level 13.4g/dL (11 to 16g/dL), platelets 361×109/L (range: 150 to 400×109/L), and sedimentation rate 9 (range: 3 to 20mm/hour). A high resolution computed tomography (HRCT) scan showed a well-defined soft tissue density lesion, seemingly originating in the region of the middle concha and was suggestive of a middle concha mucocele (Figure A and B). Sagittal plane images excluded any intracranial extension (Figure C). Our plan was to remove the mass by endoscopic sinus surgery. Intraoperatively, we found an extensive cyst filling the right nasal cavity, originating from the middle concha. The anteroinferior and mediolateral walls of the cyst were removed, effectively marsupializing it into the nasal cavity. There was no erosion on the lateral nasal wall, ethmoid roof, or septum. His right nasal cavity was packed with NASOPORE® (a biodegradable/fragmentable, synthetic polyurethane foam; Polyganics, Groningen, The Netherlands), which was aspirated on the tenth postoperative day. The postoperative period was uneventful without any complications or synechia formation. His nasal obstruction improved remarkably in the immediate postoperative period. A postoperative HRCT examination was performed 2 months after surgery. There were no signs of recurrence or inflammation (Figure ). Histopathology revealed a benign cyst lined by ciliated columnar mucin-secreting cells with no secondary changes due to infection or hemorrhage (Figure ). On follow-up, he was disease free at the end of 18 months.


A 27-year-old nulliparous woman was admitted to the obstetrics department with preeclampsia at 29 weeks' gestation. She was following a normal course of pregnancy and complied well with her antenatal schedule, with no abnormalities detected during her visits or ultrasound scans. She was similarly well prior to becoming pregnant with no risk factors that could potentially complicate the pregnancy. The patient had previously been pregnant once, which resulted in a miscarriage, and had a notable past medical history of polycystic ovaries. She did not have a partner and stated that she wished no further involvement of the father in the pregnancy or future care of the baby, wishing to act as a single parent. This pregnancy had come after over a few years difficulty conceiving.
During the course of her investigations for preeclampsia, she was noted to have ascites on trans-abdominal ultrasound scan and a slight abnormality of her liver function tests (LFT): raised alanine transaminase (ALT). An ultrasound scan and magnetic resonance imaging (MRI) of her pelvis was thus organised which identified a large, well-defined right-sided adnexal mass measuring 15 × 18 × 13.5 cm extending into the upper abdomen, with a vascular pedicle extending from the broad ligament. A smaller mass was also noted in the left adnexa measuring 4.5 cm occurring concurrently with a thickened peritoneum and omentum (Figures , , and ). These findings prompted measurements of her tumour markers which demonstrated alpha-fetoprotein 104.3, human chorionic gonadotrophin 14007, lactate dehydrogenase 172, and cancer antigen 125 (CA-125) 1266.
The right-sided mass was connected via its vascular pedicle to the broad ligament/uterine wall but despite a clear spatial relationship, there was little evidence that the tumour was connected to the right ovary. Some images of the right ovary also seemed to be normal. Considering that the patient was largely asymptomatic, this generated a preliminary differential diagnosis of a benign broad ligament tumour with ascites, subserous fibroid with ascites, or a broad ligament fibroma with Meigs' syndrome. We were also mindful that this could be a malignant ovarian tumour.
Initial treatment plans involved a review by the oncology team with repeat radiological assessments as well as awaiting delivery with the intention to perform ovarian cystectomies in order to obtain a diagnosis in the first instance. Paracentesis had also been considered; the benefits of this were not compelling as it would not alter patient management considering that debulking would be a management mainstay of tumours of gynaecological origin. However, shortly following the initial admission, the patient underwent a caesarean section at 31 weeks' gestation due to foetal distress on cardiotocography (CTG) in which the baby was safely delivered. This procedure allowed visual inspection of this pelvis which demonstrated that by this stage, the right mass had progressed into a large 25 cm cystic lesion attached to the broad ligament and posterior wall of the uterus, with an 8 cm irregular ovarian mass on the left. The inspection of the stomach during surgery was unremarkable. Large volume ascites of 3-4 litres was also noted which was drained and sampled for cytology assessment along with omental and peritoneal biopsies.
Following delivery, the patient underwent a right salpingoophorectomy and partial left oophorectomy. Histological analysis of the peritoneum and omentum samples showed infiltration by an adenocarcinoma with areas of signet ring cell differentiation. Immunostaining revealed that the tumour cells were positive for CK7 and CK20. Frozen sections of the ovaries confirmed that this was not high-grade serous ovarian cancer.
The presence of signet cells indicates that the primary malignancy is most likely of gastrointestinal origin and hence that the ovarian masses detected are metastatic, most likely a Krukenberg tumour. This was further supported by the immunochemistry results as tumours that are immunoreactive to CK7 and CK20 suggest a gastropancreatobiliary origin []. This conclusion resulted in the decision not to perform a pelvic clearance. Blood results demonstrating deranged clotting and the presence of a large haematoma on caesarean section also made this patient an unsuitable candidate for hysterectomy.
The possibility of a colorectal or lobular breast carcinoma origin had been considered and discussed at both upper GI and gynaecology multidisciplinary team meetings. An endoscopy would ideally have been performed to confirm the working diagnosis, however the patient declined this investigation. As described above, the patient had presented in rapid decline, with life-threatening ascites and pleural effusions. Hence, we were mindful of the window of opportunity to treatment—this would undoubtedly have been narrowed with comprehensive endoscopic investigations. Furthermore, even following debulking, the patient was of Performance Stage 2. Working on the immunohistopathology report which was most in keeping with an upper GI primary, EOX chemotherapy was commenced. This allowed us to begin prompt treatment but also had the added benefit of activity against our differentials which could not, at that stage, be definitively ruled out—oxaliplatin is effective in colorectal cancer and capecitabine is effective in both breast and colorectal cancers.


The patient was an 86-year-old Japanese woman who had been regularly visiting the Department of Neurology, Shizuoka Red Cross Hospital, for the treatment of Parkinson disease; the patient had a well-maintained activity of daily living (ADL) score. A routine physical checkup was done regularly and blood tests revealed no abnormal findings. She was brought to the hospital because of low back pain and fever, and was admitted in June 2010. On day 2 of hospitalization, she began to have difficulty in moving. The level of consciousness was E3V5M6 according to the Glasgow coma scale, and she fell into shock state; her blood pressure and pulse rate was 70/30 mmHg and 75/min, respectively, and temperature was 37.8°C; the respiration was distressed (24/min). Physical examination revealed petechial hemorrhage on the soft and hard palates, right cost-vertebral angle tenderness, and numerous ecchymoses and non-palpable petechiae of the legs. A plain abdominal radiography revealed a calculus of the right ureter.
The results of the laboratory studies on day 2 in the hospital were as follows. Urinalysis showed proteinuria and the urinary sediment contained 20–29 isomorphic red blood cells per high-power field. The amount of proteinuria could not be determined because the patient rapidly became anuric in the hospital. Leukocytosis (10,900/μL), anemia (hemoglobin level of 10.6 g/dL), and thrombocytopenia (4.5 × 104/μL) were present, and immature granulocytes with cytoplasmic vacuolation and Dohle bodies were identified in the peripheral blood. Impaired coagulation was noted, including prolonged activated partial thromboplastin time (APTT, 51 seconds) and prothrombin time (PT, 18.8 seconds, 1.63 by INR), as well as increased fibrin/fibrinogen degradation products (FDP, 645 ug/mL), and plasminogen activator inhibitor 1 (PAI-1, 146.8 ng/mL). The D-dimer level, determined on day 3, was 103.4 ug/mL. Inflammatory markers were markedly elevated (CRP, 6.91 mg/dL; procalcitonin, 141.96 ng/mL). Indirect hyperbilirubinemia (1.3 mg/dL), an increase in transaminases (AST, 407 IU/L; ALT, 101 IU/L) and an elevation in the serum lactate dehydrogenase (LDH, 1160 IU/L) were also present. Laboratory data associated with renal function showed elevations in urea nitrogen (UN, 43.3 mg/dL) and serum creatinine (2.09 mg/dL). The immunological profile showed normal levels of immunoglobulin and complement, but positivity for rheumatoid factor and antinuclear antibody (ANA; ×40) was noted. Perinuclear ANCA, cytoplasmic ANCA, and anti-glomerular basement membrane antibody all tested negative. Computed tomography revealed right hydronephrosis and hydroureter due to right ureteral stone. Proteus mirabilis was isolated from both blood and urine cultures.
After admission, renal failure developed rapidly, and the level of her consciousness deteriorated. Intravenous piperacillin/tazobactam (PIPC/TAZ) 6.75 gram per day was started, and was subsequently switched to ampicillin (AMPC, 4 g/day) and gentamycin (60 mg/day, i.e., 1.7 mg/kg) based on the blood and urine culture results, followed further later by ciprofloxacin (CPFX, 200 mg/day). Anuria continued even despite the placement of DJ-ureteral catheter for the right ureteral obstruction. The laboratory profile on day 2 in the hospital fulfilled the diagnostic criteria of DIC []. A marked elevation of serum PAI-1 and a reduced protein C level were observed, indicating a secondary anti-fibrinolytic DIC state. Continuous hemodiafiltration (CHDF) was performed to remove excessive cytokines in addition to the administration of broad-spectrum antibiotics and a single infusion of antithrombin III. In response to these therapies, severe infection was successfully controlled, and DIC was well managed, as evidenced by the normalization of APTT and PT as well as the improved levels of FDP, fibrinogen and PAI-1 (Table ). Disturbed consciousness and renal failure, however, persisted with sustained thrombocytopenia, high LDH levels, anemia, and the appearance of schistocytes.
Since the patient’s infection and DIC had already been well controlled, it was conjectured that the persistent abnormalities (microangiopathic hemolytic anemia, thrombocytopenia and clinical symptoms such as neurological disturbance and renal failure) were attributable to TMA. Hence, we started plasma exchange therapy on day 7, replacing the CHDF treatment. After the commencement of plasma exchange, the level of her consciousness improved dramatically in association with several laboratory parameters including the LDH level, the platelet count and the serum haptoglobin level (Table ). The ADAMTS-13 activities measured by the well-established assay method [] on days 8 and 19 were 44% and 40.6% (normal, 70-120%) respectively (Table ); the ADAMTS-13 activity measured after the improvement of all the TMA symptoms except for renal injury was also subnormal (35.5% on day 86 and 33.0% on day 220, Table ). It is to be noted that ADAMTS-13 activity was never below 10% in our patient even during the period of high disease activity, indicating that this was not a case of typical primary TTP.
To determine the etiology of the renal disease which was unresponsive to plasma exchange, renal biopsy was performed on day 26. The specimen for light microscopy contained 15 glomeruli; 7 exhibited global sclerosis, 2 severe segmental sclerosis, and 2 exhibited only minor abnormalities. The remaining 4 glomeruli had dilated capillary loops that were filled with red blood cells (Figure -A). Aggregations of severe tubular necrosis were seen in several foci (Figure -B). One of these glomeruli had an afferent arteriole with occlusive intimal changes (Figure -C; arrowhead) and what appeared to be a small intraluminal thrombus (Figure -D; arrow). Arteriosclerotic fibrous thickening of the intima was seen in the larger arteries. Smaller interlobular arteries and arterioles, on the other hand, showed occlusion or extensive narrowing of their lumen which was interpreted to represent the sequel of TMA (Figure -E). Fibrinoid necrosis of the vessel wall was not observed. No obvious thrombi were observed in the vascular lumina except for the above-mentioned modest lesion in an afferent arteriole. Tubular atrophy and interstitial fibrosis were seen in approximately 50% of the cortical area. Immunofluorescence studies showed no immunoglobulin, complement or fibrinogen deposition in the glomeruli or the blood vessels.
Although laboratory abnormalities related to secondary TMA improved dramatically with plasma exchange, the clinical course indicated an irreversible course of the patient’s renal failure. Hence, we discontinued plasma exchange and started the patient on three-times-a-week maintenance hemodialysis beginning on day 57. TMA did not recur after the discontinuation of plasma exchange, although moderately decreased levels of plasma ADAMTS-13 activity persisted (Table ). On day 96, she was transferred to another hospital for rehabilitation and maintenance hemodialysis (Figure ).


A 41-year-old male, a recent immigrant, presented to the emergency room with swelling and pain in his neck and left arm. He had a history of rheumatoid arthritis and started treatment with infliximab, methotrexate, and high dose prednisone one year prior to admission. Six weeks prior to admission, he developed night sweats and weight loss, which was diagnosed as miliary tuberculosis by CT imaging and positive sputum culture. His tuberculosis was treated with rifampin, pyrazinamide, isoniazid, and ethambutol. His anti-TNF and steroid therapy were discontinued and replaced with hydroxychloroquine and sulfasalazine. The day before his admission, the patient noticed swelling and pain in his left neck and mild dyspnea. The swelling progressed down his entire arm over the course of the day. The patient was a lifelong nonsmoker and had no prior history of deep vein thrombosis (DVT).
On physical examination, he had a BMI of 24 and was afebrile but tachycardic to 130. He had cervical and supraclavicular lymphadenopathy. His entire left arm was erythematous, swollen, and tender to palpation. Range of motion of that extremity was reduced secondary to pain.
CT of neck revealed a thrombus within the left axillary and left subclavian veins extending to the proximal left brachiocephalic vein, in addition to enlarged right and left supraclavicular lymph nodes, without obvious vascular compression (). CT angiography of chest showed pulmonary emboli involving the right lower lobe in addition to previously noted nodular opacities of miliary tuberculosis ().
His hemogram was significant for normocytic anemia and neutrophilia. Electrolytes, renal and liver function tests, hepatitis panels, and blood cultures were normal and his acid-fast smear was now negative. His coagulation profile was normal except for an elevated D-dimer of greater than 1000 ng/mL. An extensive work-up for thrombophilia was unremarkable with normal lupus anticoagulant, silicone-clotting test, Factor V Leiden, prothrombin 20210, Cardiolipin IgG, IgM 5, and beta-2 glycoprotein.
The patient was treated with enoxaparin and his swelling and dyspnea subsided. A warfarin regimen was attempted at 5 mg, but his INR remained 1.2. The patient was subsequently discharged being on rivaroxaban, prednisone 20 mg, and trimethoprim-sulfonamide prophylaxis, in addition to his antituberculosis regimen.


A 62-year-old Caucasian female with a history of diabetes mellitus was hospitalized for acute onset of shortness of breath. She was found to be hypoxic, and chest X-ray showed bilateral interstitial infiltrates. She was incidentally found to have abnormal liver tests in the form of elevated aminotransferases and hyperbilirubinemia (). The patient did not give a history of prior liver disease, did not drink alcohol, and had no risk factors for acute viral hepatitis. Her most recent previous liver tests (from 3 years ago) had been completely normal. Physical examination revealed jaundice but no splenomegaly, asterixis, or other stigmata of chronic liver disease. The following tests were negative or normal on evaluation—viral hepatitis serologies, serologic markers of autoimmune hepatitis, serology for Lyme disease, HIV, CMV, and EBV serologies. Serum ceruloplasmin was normal, and testing for alpha1 antitrypsin deficiency was negative. Ultrasound of the abdomen demonstrated fatty infiltration with no evidence of portal hypertension and no evidence of biliary ductal obstruction.
A detailed medication history was obtained to identify potentially hepatotoxic medications. The patient reported using metformin at a stable dose on a daily basis for several years. Two weeks prior to hospitalization, she had started taking a new over-the-counter, multiingredient arthritis supplement called Move Free. She was using the product as directed, taking four tablets per day for two and a half weeks and had tapered down to two tabs a day for four days prior to hospitalization. The medication was noted to contain glucosamine, chondroitin, MSM (methylsulfonylmethane), Chinese Skullcap, black catechu, and maltodextrin. The herbal supplement, Chinese Skullcap has been implicated in causing drug induced liver injury in other cases.
A liver biopsy (Figures and ) was performed which showed histologic features of a panacinar hepatitis, with expansion of the portal tracts by a mixed chronic inflammatory infiltrate composed of lymphocytes, eosinophils, and plasma cells. The lobular parenchyma showed foci of inflammation with scattered eosinophils and acidophil bodies. There was mild steatosis (15% to 20%) with features of a mild superimposed steatohepatitis present without established fibrosis. The combination of clinical history, negative serologies, and biopsy findings strongly favored adverse drug reaction.
At initial presentation, the patient did have significant respiratory distress and required oxygen support. She did not have any fever or cough. Computed tomography (CT) of the chest revealed bilateral ground glass opacities in the upper lobes. Viral and bacterial testing failed to identify an infections etiology to her pulmonary infiltrates. It is possible that her pulmonary manifestations were also related to the Chinese skullcap.
The patient discontinued the supplement and her hepatitis slowly improved over the next several weeks. In 2 weeks her AST was down to 668 from 893 and ALT was down to 1144 from 1247. After 8 weeks the liver enzymes had completely normalized (). She required home oxygen for a few weeks after discharge and was eventually able to discontinue this.


A 50 year old woman was referred, 15 years after skull based surgery resulting in a right complete facial paralysis. She had atrophy, severe elongation and drooping of right side of face, abundant skin and soft tissue accumulation below the right labial commissure. Severe facial deviation and distortion to normal (left) side were present ().
Endoscopic brow elevation was performed, with overcorrection of the paralyzed side (a probable complication is in- creased exposure of eye). Right tarsal strip for the right lower eyelid and tarsorrhaphy were done. A face lift incision was initiated at the root of the helix and continued to the preauricular crease, curved around the earlobe and back and up rotated to the mastoid tip. Considering the history of radiotherapy to the skull base and in- creased risk of skin flap necrosis, a sub-SMAS (superficial musculoaponeurotic system) flap was elevated in preauricular region. Flap elevation was continued to ipsilateral nasolabial fold and philtrum. In doing so a tunnel was created from tragus and angle of mandible to mid portions of upper and lower lips. In conventional masseteric transfer, inferior and middle portions of anterior two thirds of masseter muscle were detached from mandible and were used to elevate oral commissure. Also attachment of masseter to the inferior border of the body of mandible was elevated with masseter to facilitate sutures to the distal part of flap. The most common disadvantage of the conventional procedure was muscle elongation due to the weight of face postoperatively, and some drooping would occur in time. This led to a partial loss of the reconstruction results. In this modification, masseter muscle was elevated in continuity with periosteum of the lateral surface of mandibular ramus as a unit. Small incisions were also made in the centre of vermilion of both lips and connected to the tunnel. The distal end of the masseteric flap was divided to three parts and rotated anteriorly toward central lip incisions. Anterior part was sutured to lower philtrum and vermilion of upper lip, posterior part to lower lip vermilion, and middle part to right oral commissure. One centimeter overcorrection was considered appropriate for reconstruction.
Massteric transfer with the underlying mandibular periosteum as a unit, augmented the muscle flap and prevented future elongation. It seemed a new modification for masseteric transfer that produced better results with time. shows one year after surgery with counter pressure of upper and lower jaws. The patient was edentulous, so some internal distortion of inferior right lower lip behind the upper lip was seen.


A 65-year-old man presented to the hospital with 1-week history of bloody and foul smelling discharge from his groin. The patient had initially noticed a small lesion of approximate dimension of a pea in his right inguinal area about 20 years ago. Since the lesion did not bother him at that time, he did not seek medical care until when he started to notice blood oozing from it. The lesion had increased in size multifold over the years and had extended into the left groin and the perineal region. It was not painful, but caused some discomfort mainly during sitting. He reported no fevers, loss of weight, urinary symptoms, or difficulty in defecation and denied any other skin lesions elsewhere. All other reviews of systems were essentially unremarkable. He was in a monogamous relationship with his wife who had passed away 10 years prior to presentation. He denied previous promiscuous behavior.
On examination, patient was afebrile and hemodynamically stable. An extensive, foul-smelling cauliflower-shaped lesion was apparent in the inguinal regions bilaterally. It measured around 15 cm in width in each groin along the maximum dimension, and about 40 cm in length, extending from the waist line through the groin into the intergluteal cleft towards the rectum (). It had also involved the lateral aspects and base of the scrotum. The lesion was not tender. Remainder of the physical examination was normal. Laboratory studies revealed leukocytosis (white blood cell count 15,300 per mm3), hemoglobin 14.3 gm/dL, and platelet count 284,000 per mm3. Renal and liver function tests were normal.
Human immunodeficiency virus and rapid plasma reagin serological tests were nonreactive. Urine analysis and blood cultures were unremarkable. Contrast enhanced computed tomography of chest, abdomen, and pelvis was done that did not reveal any regional lymph node involvement or evidence of distant metastasis.
Based on the clinical presentation, a diagnosis of giant condyloma acuminatum of Buschke-Lowenstein was suspected. The lesion was radically excised and the entire specimen was sent for gross pathological examination () and histopathology (Figures and ). Grossly, the tumor appeared as fungating, exophytic, cauliflower-shaped like mass. It was hard in consistency and gave the look of a bulky tumor. On histopathology, there was evidence of epidermal hyperplasia, hyperkeratosis, and papillomatosis (). Koilocytes (vacuolated cells with clear cytoplasm and perinuclear halo), a result of infection from HPV, were seen on higher magnification (). There were no histopathologic features of malignant transformation.
A final diagnosis of condyloma acuminata of BLT (superficially invasive verrucous carcinoma with pathological staging T1) was made. The patient has not had a recurrence of the tumor for 3 years from the time of radical excision.